A new play tackles the politics around race and gender in science Can “race” be gleaned from our genes? Concern over the emerging trajectories of genetics research has led to ongoing debates about how to characterize and interpret genetic variation. Despite the mantra that humans share 99.9% of our genetic makeup, there is increasing interest in identifying the relatively small percentage difference that distinguishes individuals. Therein lies the paradox: if we are all the same, why do we continue to search for the ways in which we differ from one another? We can take an essential first step toward addressing this paradox by acknowledging the often conflicting stakes for individuals and groups in debates that center around genes, science, and race. Whose genes will be studied? For what purpose? And who has the authority to decide?These stakes are laid bare by Cassandra Medley in her play “Relativity,” which ran at the Magic Theater in San Francisco this spring, in a production directed by Edris Cooper-Anifowoshe. The play focuses on the inner conflict of a young scientist, an African American woman who tries unsuccessfully to straddle the opposing world views of her profession and her family. In “Relativity,” Kalima Davis is a postdoctoral fellow in a prestigious stem cell laboratory on the East Coast. Her impeccable academic pedigree distinguishes Kalima as a rising researcher, and she is one of the few women and African American scientists working in the field. Kalima is also the devoted daughter of the charismatic psychotherapist Claire Reid, who directs the “Leon Davis Foundation,” which Kalima's late father dedicated to the belief that neuropeptide melanin, found in “people of color,” enhances intelligence, athleticism, and emotional sensitivity. This theory also points to the lack of melanin among lighter skinned individuals as a cause of “white racism.” Kalima, who has inherited co-directorship of her father's foundation, is asked by her mother to offer “scientific proof” of the melanin theories and to discount the assertion that all groups are genetically similar.At issue in “Relativity” is the struggle over what constitutes a valid belief. Reid suggests to Kalima that “science is not the sole province of what the ‘West’ defines it to be,” and refers to Chinese acupuncture, Hindu Chakra, and tribal African shamanism as examples of legitimate “sciences.” But the power of Western science to trump other interpretations of lived experience has become all too clear in the genomic era. Truth is excavated from the human body, where genes emerge as the iconographic oracles of our past, present, and future. As Kalima recounts, “We can't get around it. DNA is fact.” Nonetheless, Kalima naively attempts to find a way to retain these opposing epistemologies. The futility of this dual position is made apparent by the arrival of Iris Preston, an African American senior scientist who has taken over as the new head of Kalima's lab. Preston, a highly vocal critic of Claire Reid and melanin theories, serves as a formidable apostle of the scientific method. Shortly after her arrival, Preston convenes members of her new lab to filter those seeking financial and other derivative rewards from the truly devoted, who are motivated solely by their “sense of wonder and amazement” and their desire to “cultivate what Einstein referred to as ‘holy curiosity.’” She makes plain that science, like all ideologies, demands consummate faith and unwavering piety.Kalima's struggle to claim her “true lineage” is much more than a simple choice between her biological mother (Reid) and her intellectual mentor (Preston). Her plight forces her to explore the meaning of justice. The contrast between melanin theories and genomic research, initially stark, blurs as it becomes increasingly clear that both Reid and Preston seek to use their “science” to redress race-related disparities. Citing a history of racism, including the historically well-documented Tuskegee Syphilis Study, Reid asks rhetorically whether genetics research will result in a “genetically modified” white upper class and a lower, dark-skinned “natural birth class”? At stake are issues of power and trust, and the question of whether new genetic technologies will close the gaps between groups or make them wider. Some postulate that the “new genetics” will render conventional notions of race obsolete. However, it is doubtful that such a color-blind utopia will be won through the sequencing of genes without a serious engagement with the differences that lie outside cell walls. A social infrastructure of inequality that mediates race through nutritional deficits, exposure to pollutants, and the use of the emergency room as the sole venue for healthcare will not be rehabilitated through gene therapy or pharmacogenomics.Preston seeks to use her stature in science to focus on the inequities within the academy. Encouraging Kalima to appear with her on a television program about stem-cell research, Preston urges her to imagine the milestone of “not just one, but two black women scientists, holding forth among the usual cadre of white males.” As one of the rare, highly scrutinized, “minority” scientists, Kalima embodies a “double jeopardy.” She must prove that she is worthy of her position—that she is as good, if not better, than her “white” peers—yet she must always be “remembering from whence she came.” When Dan, a white colleague in Kalima's lab who is also her boyfriend, hears that Preston has chosen Kalima to appear with her on television, he jealously accuses her of benefiting from preferential treatment. The play's depiction of this assertion of “reverse racism” questions the legitimate use of race in evaluating promotion and achievement in science. What is apparent is that race, while an ever-present subject, is often presented as the antithesis of conventional notions of a color-blind meritocracy. Left to linger is the critical question: does merely identifying differences among groups constitute an act of racism? Can statements of racial differences be neutral, unfettered by a relative hierarchy?Medley throws into stark relief the politics around race and gender in science. She illuminates how an individual's dilemma transcends the private realm; personal decisions are never truly “personal,” but are inherently public because they always have wider social repercussions. In the fateful confrontation between Kalima and her mother, Reid challenges her daughter to “grow up” and to risk her disapproval. A similar challenge can be issued to those who have inherited the “new genetics”—to vanquish the continuing paradox of reciting a “mantra of sameness” all the while searching for meaningful differences. In “Relativity,” Medley serves us a cautionary tale of the costs of our chronic ambivalence about the critical issues of race and justice in science. A good first step is to recognize that the search for meaning in human difference is inseparable from the struggle over the moral order in which we live.To underestimate the power of science to define our social agenda is to lose an opportunity to determine our future course. We only need to look to history as our proof.


Trp cage is a recently-constructed fast-folding miniprotein. It consists of a short helix, a 3,10 helix and a C-terminal poly-proline that packs against a Trp in the alpha helix. It is known to fold within 4 ns.High-temperature unfolding molecular dynamics simulations of the Trp cage miniprotein have been carried out in explicit water using the OPLS-AA force-field incorporated in the program GROMACS. The radius of gyration (Rg) and Root Mean Square Deviation (RMSD) have been used as order parameters to follow the unfolding process. Distributions of Rg were used to identify ensembles.Three ensembles could be identified. While the native-state ensemble shows an Rg distribution that is slightly skewed, the second ensemble, which is presumably the Transition State Ensemble (TSE), shows an excellent fit. The denatured ensemble shows large fluctuations, but a Gaussian curve could be fitted. This means that the unfolding process is two-state. Representative structures from each of these ensembles are presented here. Understanding the mechanisms behind protein folding, which is one of the most fundamental biochemical processes, is proving to be a challenging task for biochemists and biophysicists. Recent developments in instrumentation and methodology have enabled us to take major steps forward in comprehending the dynamics of proteins and peptides at the molecular level. Protein engineering methods such as Phi-value analysis  and variProteins are composed of two major secondary structural elements, helices and sheets, which, along with loops, pack together to form super-secondary and tertiary structures. Trp cage is a novel, and a highly stable, mini-protein fold. A 20-residue Trp-cage miniprotein has been designed [Molecular dynamics simulations, which make use of classical Newton mechanics to generate trajectories, are playing an ever-expanding role in biochemistry and biophysics due to substantial increases in computational power and concomitant improvements in force fields. In particular, the contribution of such studies to protein folding is immense . As poinDespite being a new mini-protein construct, the Trp cage motif has attracted considerable computational analysis. Folding simulations of this protein in explicit water have been carried out using what is known as the Replica Exchange Method. A two-state folding mechanism has been proposed and free energy surfaces have been determined . MoreoveMolecular dynamics simulations of the Trp-cage mini-protein construct (PDB ID: 1L2Y) were carried out using the OPLS-AA force-field incorporated in the freely available program, GROMACS. The simulations were carried out at 498 K, at which temperature the unfolding process is favored. This temperature provides a good description of the unfolding process, at least in respect of CI2 and the homeodomain of engrailed . It is aIt can be seen that the RMSD figure  of the eAfter 800 ps, there is a jump in the values of both RMSD and Rg. The new value remains constant until about 3200 ps. This state is characterized by complete annihilation of the cage. The W6 is released from the Pro cage and becomes completely "solvent-exposed". It must be noted that the use of the term "solvent exposed" is not entirely appropriate in this context as there is no real change in the solvent-accessible surface area of the W side-chain. However, the point is that, this W is no longer protected by the proline cage. Native contacts are retained in the form of a salt-bridge between D9 and R16. Representatives of this ensemble are shown in figure After 3200 ps, a further jump in RMSD and Rg is observed leading to a state where these values fluctuate markedly. This highly disordered state, showing a measure of heterogeneity, is the denatured ensemble, in which the salt-bridge interaction that characterized the intermediate state is also lost. There is a significant jump in the distance between the Asp9 and Arg 16 sidechains after this time. As a result, there are no native contacts in this state. This is represented by structures in figures In this manuscript, I also discuss a new method for identifying sufficiently populated states during the course of an MD simulation. The idea is that each state is to a large extent topologically different from any other state and can be characterized by an approximately Gaussian distribution of the radius of gyration. This is to be expected because each state lies at a defined height in the free-energy well. In this simulation it can be observed that transitions from one state to another are characterized by a significant jump in the radius of gyration. The distribution of the radius of gyration was determined for each of the three states and for the entire time-evolving system. For each of the three ensembles and for the entire time duration, the distribution was calculated over the ranges of values shown in table High-temperature unfolding molecular dynamics simulations of a Trp cage miniprotein construct have been carried out. This has shown that the process is two-stage, akin to the folding process results . The thrThe starting structures for the simulations were obtained from PDB 1L2Y . The firThe author(s) declare that they have no competing interests.


The maternal circulation to the human placenta is not fully established until 10–12 weeks of pregnancy. During the first trimester the intervillous space is filled by a clear fluid, in part derived from secretions from the endometrial glands via openings in the basal plate. The aim was to determine the activity of the glands throughout the first trimester, and to identify components of the secretions.Samples of human decidua basalis from 5–14 weeks gestational age were examined by transmission electron microscopy and immunohistochemically. An archival collection of placenta-in-situ samples was also reviewed.The thickness of the endometrium beneath the implantation site reduced from approximately 5 mm at 6 weeks to 1 mm at 14 weeks of gestation. The glandular epithelium also transformed from tall columnar cells, packed with secretory organelles, to a low cuboidal layer over this period. The lumens of the glands were always filled with precipitated secretions, and communications with the intervillous space could be traced until at least 10 weeks. The glandular epithelium reacted strongly for leukaemia inhibitory factor, vascular endothelial growth factor, epidermal growth factor, transforming growth factor beta, alpha tocopherol transfer protein, MUC-1 and glycodelin, and weakly for lactoferrin. As gestation advanced uterine natural killer cells became closely approximated to the basal surface of the epithelium. These cells were also immunopositive for epidermal growth factor.Morphologically the endometrial glands are best developed and most active during early human pregnancy. The glands gradually regress over the first trimester, but still communicate with the intervillous space until at least 10 weeks. Hence, they could provide an important source of nutrients, growth factors and cytokines for the feto-placental unit. The endometrium may therefore play a greater role in regulating placental growth and differentiation post-implantation than previously appreciated. The realisation that the maternal circulation to the human placenta is extremely limited prior to 10–12 weeks of pregnancy prompted us to investigate other potential sources of fetal nutrition during the first trimester . During More recently, it has been appreciated that the secretions may perform wider functions beyond the simple provision of nutrients. Some components, such as glycodelin, have potent immunosuppresive properties , while oIn the human histiotrophic nutrition has always been considered to be of little importance for two principal reasons. Firstly, the invasive form of implantation displayed by the human blastocyst removes it from the uterine lumen, and hence it was believed the uterine secretions, by day 7–10 post-fertilisation. Secondly, the contemporaneous appearance of maternal erythrocytes within the lacunar spaces of the syncytiotrophoblastic mantle has been widely interpreted as evidence of early onset of the maternal circulation, and hence haemotrophic exchange ,15. HoweThe aim of this study was therefore to examine the secretory activity of the endometrial glands within the decidua basalis both morphologically and immunohistochemically over the first trimester in order to assess their potential contribution to fetal nutrition and placental development.Samples of decidua basalis were obtained with informed written consent from patients undergoing surgical termination of normal pregnancies at University College Hospital, London. The study had been approved by the University College London Hospitals Committee on the Ethics of Human Research. Samples were obtained under ultrasound guidance, and were available from 30 cases ranging in gestational age from 5 weeks to 14 weeks (median age 9 weeks). Gestational age was estimated from the crown rump length of the fetus. Immediately after removal the tissues were fixed by immersion for 2 hours in either 4% paraformaldehyde in 0.1 M PIPES buffer for immunohistochemistry or 2% glutaraldehyde for electron microscopy, or frozen in OCT medium.2O2 for 30 min, the sections were incubated with non-immune serum for 20 min. The primary antibodies , permeabilised in TBS containing Triton X-100 (0.1%) and Tween 20 (0.1%) (TBS-TT) for 30–60 min and blocked in 5 % goat serum for 30 min at room temperature. A mixture of a rabbit polyclonal and a mouse monoclonal antibody diluted in TBS-TT was applied, and sections were incubated overnight at 4°C. Negative control sections were left at the blocking stage and were not covered with primary antibodies. After three 10-minute washes in TBS-TT, sections were incubated for 1 hr at room temperature with a mixture of fluorescent secondary antibodies, containing goat anti-rabbit Alexa 488 and goat anti-mouse Alexa 568  in TBS-TT. Sections were washed in TBS-TT as before and then twice in distilled water for 5 min and subsequently mounted in Vectashield mounting medium containing DAPI (Vector, UK).Frozen sections were used for dual labelling with anti-cathepsin D (rabbit) and glycodelin (mouse). Samples were frozen in cryoembedding medium. Sections (10–12 μm) were cut on a Reichert cryomicrotome, air-dried, fixed briefly in cold methanol/acetone (at -20°C) and permeabilised in TBS-TT for 30–60 min. All subsequent immunolabelling steps were carried out as with the paraffin embedded sections. Images were captured using a Leica confocal microscope (LeicaTCS-NT, Leica Instruments GmbH, Germany).Glutaraldehyde fixed tissues were secondary fixed in 1% osmium tetroxide for 1 hour, and embedded in Araldite epoxy resin. Semi-thin sections (1 μm) were stained with methylene blue, whereas ultra-thin sections (50 nm) were counterstained with uranyl acetate followed by lead citrate and viewed using a Philips CM100 microscope (Eindhoven, The Netherlands).The Boyd Collection housed within the Department of Anatomy, University of Cambridge, contains a number of placenta-in-situ specimens. Only those with no recorded history of pathology were reviewed, and twelve specimens met this criterion. The gestational age  was estimated from the recorded crown-rump length , and ranAll analyses were performed using Statview (SAS Institute Inc., Cary, USA).r = -0.644, P = 0.0216). As gestation advanced there was also increasing variability in the thickness of the endometrium across the placental bed, reflecting the formation of placental septa. The profiles of the glands became smoother and more regular, but they still contained precipitated secretions , VEGF and MUC-1 at all gestational ages from 5 to 14 weeks Figure . In the 3), although many of the decidual cells also reacted positively as gestational age increased  and transforming growth factor beta , for although the glandular epithelium initially displayed strong reactivity, the intensity reduced considerably by 9–10 weeks. By contrast, in the older specimens the cells immediately beneath the epithelium reacted strongly. As these cells also reacted positively for CD56 it was assumed they were NK cells Figures .Immunoreactivity for lactoferrin was weak even in the earliest specimens, although occasional cells reacted strongly. In the older specimens only faint staining could be identified Figure .In all cases the negative controls showed no staining.In order to determine whether the glandular secretions taken up by the trophoblast enter the digestive pathway frozen sections of first trimester villi were dual-labelled for glycodelin, a glandular product, and cathepsin D, a marker of the lysosomal pathway. In the syncytiotrophoblast numerous vesicles immunoreactive exclusively for glycodelin were observed within the superficial layer of the syncytioplasm abutting the intervillous space, whereas lysosomes positive only for cathepsin D were observed in the basal region. In the midzone of the syncytioplasm the two labels were co-localised, indicating lysosomal fusion with the glycodelin-containing vesicles Figure .It is clear from this study of placenta-in-situ specimens that the uterine glands are still well-developed and highly active at 6 weeks of pregnancy, and that although there is considerable individual variation they gradually regress, both in terms of their length and the height of their epithelium, as the first trimester advances. Some of this variation may reflect differences in the thickness of the endometrium across the placental bed, for it was generally thinnest in the centre and thicker towards the periphery. Sampling at different sites may therefore yield different measurements. Nonetheless, by the start of the second trimester the endometrium beneath the placenta is very thin, the glandular epithelium is cuboidal and secretory organelles are no longer predominant. Indeed, the accumulations of osmiophilic material within the cytoplasm are reminiscent of lipofuschin, a characteristic of involuting or aging cells. These observations are consistent with a gradual shift from essentially histiotrophic nutrition of the human conceptus during the early first trimester to haemotrophic nutrition towards the start of the second trimester ,20.We previously reported that at 6 weeks gestational age the glandular epithelial cells closely resemble those during the luteal phase of the cycle, with large accumulations of glycogen within the apical portions of the cell ,21. In t3 can modulate trophoblast differentiation between the proliferative and invasive phenotype [Besides acting as a source of nutrients our results also demonstrate that the glands express a wide variety of growth factors and cytokines, and so may play an important role in regulating placental development as in other species. Receptors for EGF have been localised immunohistochemically to the cytotrophoblast cells in the earliest stages of pregnancy, and on the syncytiotrophoblast in later gestation ,28. Thishenotype . HistiotAnother group of proteins expressed by the glandular epithelium is that of transport carriers. TTP is a cytosolic protein first identified in the liver, but which has recently also been reported in the syncytiotrophoblast of the human placenta ,36. The Endometrial secretions may also modulate maternal immunological responses to the placental tissues. Thus glycodelin, which is released into the intervillous space, is immunosuppressive and functions as a direct T-cell inhibitor ,42. As gBecause insufficient decidualization could have an impact on implantation and placentation, evaluation of the endometrial morphology by ultrasound has generated a lot of clinical interest. An endometrial thickness of 8 mm or more is considered to be favourable for implantation in humans , althougAttempts to correlate functional activity of the glands with pregnancy outcome have also met with mixed success. Thus, whilst reduced concentrations of MUC-1, LIF and glycodelin in uterine flushings have been reported in women suffering recurrent miscarriages ,52, exprJH performed the tissue processing and colourimetric immunohistochemistry. TC-D performed the confocal immunofluoresence and dual-labelling. EJ performed the clinical procedures and collection of samples. GJB conceived the study and performed the electron microscopy and morphometric analysis.


There are multiple studies in different countries regarding the prevalence of vitamin D deficiency. These studies showed high prevalence of vitamin D deficiency in Asian countries. This study tries to elucidate the prevalence of vitamin D deficiency and its influencing factors in population of Tehran.1210 subjects 20–64 years old were randomly selected. 25 (OH) D serum levels were measured. Duration of exposure to sunlight, the type of clothing and level of calcium intake and BMI were quantified based on a questionnaire.A high percentage of vitamin D deficiency was defined in the study population. Prevalence of severe, moderate and mild Vitamin D deficiency was 9.5%, 57.6% and 14.2% respectively. Vitamin D serum levels had no significant statistical relation with the duration of exposure to sunlight, kind of clothing and BMI. Calcium intake in the normal vitamin D group was significantly higher than the other groups (714.67 ± 330.8 mg/day vs 503.39 ± 303.1, 577.93 ± 304.9,595.84 ± 313.6). Vitamin D serum levels in young and middle aged females were significantly lower than the older group.Vitamin D deficiency has a high prevalence in Tehran. In order to avoid complications of vitamin D deficiency, supplemental dietary intake seems essential. Vitamin D is an essential element for establishing and maintananing bone structure. Vitamin D deficiency results in rickets and osteomalacia. Even slight vitamin D deficiency results in secondary hyperparathyroidism and increased bone resorption ,2. In adVitamin D is supplied by consumption of vitamin D-rich foods and by vitamin D synthesis in skin.Natural nutrient materials are not a sufficient source of vitamin D to supply the body requirements; therefore where there is no supplementation of foodstuffs, the main source for vitamin D is produced by UV light ,5.Regarding the significant role of sunlight in vitamin D synthesis, it is quite logical to suggest low prevalence of vitamin D deficiency in tropical countries. However the studies carried out in the preceding two decades have shown a high prevalence of vitamin D deficiency in tropical countries such as China, Turkey, India, Iran and Saudi Arabia -14. The The present study is a part of a national project of prevention, diagnosis and treatment of osteoporosis that investigates the prevalence of vitamin D deficiency and its influencing factors in the population of Tehran.1272 healthy men and women aged 20–69 years were selected based on randomized clustered sampling from 50 blocks in Tehran.Exclusion criteria were known hepatic or renal disease, metabolic bone disease, malabsorption, sterility, oligomenorrhea, type I diabetes, hypercortisolism, malignancy, immobility for more than one-week, pregnancy, lactation, and medications influencing bone metabolism. The study protocol was approved by research ethics committee of Endocrinology & Metabolism Research Center (EMRC). Sampling was performed after taking informed consent at the beginning of 2001 in the subjects place of residence. 1210 of 1272 selected subjects participated in this study (response rate was 95%). One fasting blood sample was taken from each participant in his/her place of residence. Sample centrifuge and serum extraction were done in the field. Then samples were sent to the EMRC laboratory for analysis and were frozen immediately. 25-hydroxy vitamin D (25(OH) D) level was measured with RIA method (Biosource Europes.A,Ò). Normal range for serum vitamin D (25(OH) D) was 23 to 113 nmol/l. Serum PTH measurement was done using RIA method (Diasorin,Ò). Normal range for PTH is 13 to 54 nmol/l. Interassay and Intrassy for 25(OH) D were 8%, 6.8% and for PTH were 8.9% and 6.1% respectively.The subjects were asked to complete a questionnaire at the time of bone mineral densitometry analysis.The questionnaire included details of duration of exposure to sun light in previous month , sunscreen cream usage, clothing (exposure of hand and face or more than). In order to quantify the level of vitamin D and calcium consumption in the previous month, a food frequency questionnaire which was designed and standard by the Iranian Nutrition Institute was completed. Height and weight were measured at this stage.2 test Kruskal-Wallis were used.25(OH)D equal or less than 12.5 nmol/l was considered as severe vitamin D deficiency or group 1 and vitamin D more than 12.5 nmol/l and less than 25 nmol/l was considered as moderate deficiency or group 2 . PTH chaIn order to quantify serum levels of vitamin D and other biochemical parameters, serum samples were taken from 1210 subjects (response rate was 95%). 41% of subjects were male and 59% were female. Age and sex distribution of participants are shown in table Figure Figure Serum levels of vitamin D in females above 60 years was higher than in other age groups . Vitamin D serum levels in females between 20–29 years and 30–39 years was less than other age groups (P < 0.001). Median vitamin D level in females in age range of 20–29 years and above 60 years was 17 nmol/l and 39 nmol/l, respectively.Prevalence of high level of vitamin D (more than 150 nmol/l) in 60–69 years old female age group was significantly more than other age and sex group (P < 0.01). In recalling for bone densitometry, 666 returned (55% of study population) in whom the effect of influencing factors was evaluated. Table In our study the prevalence of severe and moderate vitamin D deficiency was 9.5 % and 57.6%, respectively. Mild vitamin D deficiency had a prevalence of 14.2%.Multiple studies have been carried out about the prevalence of vitamin D deficiency but they were mostly limited to a small sample size or assessed a specific age group . In countries where vitamin D fortified foodstuffs are available (USA and some Scandinavian countries), prevalence of vitamin D deficiency is between 1.6–14.8% in different age groups -18. In oFonseca and colleagues, demonstrated vitamin D level above 10 ng/ml in only 3 saudian females out of 31 . SedraniMost studies have shown higher prevalence of vitamin D deficiency in the elderly -18. EldeSubjects who took vitamin D in the sampling period were excluded from the study, but those who had taken vitamin D in the preceding months were not omitted. Vitamin D has a long half-life and its frequent prescription especially in elderly women with musculo-skeletal complaints can explain differences in serum vitamin D. Regarding the essential role of sunlight in vitamin D synthesis, it is quite unexpected to see a high prevalence of vitamin D deficiency in countries such as Saudi Arabia. Different hypotheses can be made such as insufficient sun exposure, clothing habits, hyper pigmentation, air pollution, insufficient intake of vitamin D and special dietary habits . AlthougIn the present study sun exposure was not significantly different between subjects with vitamin D deficiency and those with normal vitamin D status.Although there is sufficient sunlight in all seasons in Saudi Arabia, Sedrani showed that half of people who had more than 30 minutes of sun exposure had vitamin D less than 8 ng/ml (20 nmol/l) . Holick Sedrani showed 70% vitamin D deficiency in males compared with30 % in young females in spite of greater clothing in females .Another hypothesis says that air pollution prevents enough UV exposure to skin. Insufficient vitamin D intake is another hypothesis for high prevalence of vitamin D deficiency in Asians.Insufficient dietary supplies of vitamin D in countries where foodstuffs are not supplemented, leads to generally low dietary intake of vitamin D. In the Omdahl study, daily vitamin D intake in elderly healthy women was 54 units . Our stuAverage calcium intake was 660 ± 350 mg/day in this study. There was no significant difference in dietary calcium intake among the different vitamin D groups. Although consumption of phytates and animal-derived proteins was not investigated in present study, high dietary consumption of phytates and low dietary intake of animal proteins is one of the suggested hypothesis for vitamin D deficiency ,26,27.There are other hypotheses to explain vitamin D deficiency among Asians. Awumey et al showed higher activity level of 24-hydroxylase in fibroblasts of Indian-Americans compared with controls . TherefoGiven the high prevalence of vitamin D deficiency in Iran, effective solution to overcome its consequences seems indispensable.None declared.The pre-publication history for this paper can be accessed here:


To study the effect of prophylactic application of mitomycin-C on haze formation in photorefractive keratectomy (PRK) for high myopia.Fifty-four eyes of 28 myopic patients were enrolled in this prospective study. All eyes were operated by PRK followed by 0.02% mitomycin-C application for two minutes and washed with 20 ml normal saline afterwards. All eyes were examined thoroughly on the first 7 days and one month after surgery; 48 eyes (88.9%) at 3 and 6 months postoperatively. Hanna grading  was used for assessment of corneal haze.th postoperative month compared to the preoperative data.The mean spherical equivalent refraction (SE) was -7.08 diopters (D) ± 1.11 (SD) preoperatively. Six months after surgery, 37 eyes (77.1%) achieved an uncorrected visual acuity (UCVA) of 20/20 or better, all eyes had a UCVA of 20/40 or better and 45 (93.7%) eyes had an SE within ± 1.00D. One month postoperatively, 2 eyes (3.7%) had grade 0.5+ of haze, while at 3 and 6 months after surgery no visited eye had haze at all. All eyes had a best corrected visual acuity (BCVA) of 20/40 or better and there were no lost lines in BCVA by 6 months after surgery. In spatial frequencies of 6 and 12 cycles per degree contrast sensitivity had decreased immediately after PRK and it had increased 1.5 lines by the 6The results show the efficacy of mitomycin-C in preventing corneal haze after treatment of high myopia with PRK. This method- PRK + mitomycin-C – can be considered an alternative treatment for myopic patients whose corneal thicknesses are inadequate for laser in situ keratomileusis (LASIK). However, the results should be confirmed in longer follow-ups. In refractive surgery, patients with -5.00 diopters (D) myopia or more and corneal thicknesses less than 500 μm are not suitable candidates for laser in situ keratomileusis (LASIK) or conventional photorefractive keratectomy (PRK) due to the inadequate corneal thickness and risk of haze.-13 ThereIn this prospective non-controlled clinical study we have assessed the prophylactic application of mitomycin-C on regression and haze in PRK performed on patients with high myopia (SE ≥ -5.00 D).Fifty-four eyes in 28 patients with a spherical equivalent refraction over -5.00 D were included in this prospective non-controlled clinical study. Since the residual stromal bed thickness under the flap after LASIK would be less than 250 μm, no eye had an appropriate corneal thickness for this procedure. In planning PRK, the post-ablation corneal thickness was calculated to be greater than 350 μm. Exclusion criteria in this study were systemic or ocular disease with the potential to interfere with the healing process of the cornea, such as collagenosis, diabetes, dry-eye syndrome, anterior or posterior uveitis, ectatic diseases such as keratoconus, and also corneal dystrophy or degeneration, glaucoma, retinal diseases, lens opacity, history of severe ocular trauma, and previous ocular surgery. The study was approved by the Research and Ethics Committee of the Noor Vision Correction Center. Before the operation, the nature of the procedures, their results and complications were thoroughly explained to all patients and they were asked to read and sign a formal informed consent in their native language.All treatments were performed between April and October 2002. All eyes underwent the standard PRK procedure by two surgeons with extensive experiences with PRK. Patients received topical anesthesia without systemic sedation. Pre-incision of the corneal epithelium was made using a microtrephine with an 8 mm diameter and 70 μm deep calibrated blade (Janach, J 2900S). The epithelium was removed mechanically with a hocky knife. Then, the ablation was performed using a Technolas 217-C excimer laser (Bausch and Lomb, CA, USA). In all treatments, the overall ablation diameter was 8.4 to 8.9 mm and consisted of a central optical zone of 5.5 to 6.0 mm respectively by a 2.9 mm transition zone. Considering our previous experiences, eyes receiving mitomycin-C were intentionally under-corrected by 5 % compared with LASIK nomogram.Immediately after laser ablation, a single topical application of mitomycin-C 0.02% (0.2 mg/ml) diluted in balanced salt solution was instilled in each eye with a weck sponge placed over the ablated stroma for 2 minutes. The corneal surface and the entire conjunctiva were then vigorously irrigated with 20 ml cold normal saline to remove the residual mitomycin-C. At the end of the procedure, a bandage contact lens was applied which was removed after three days.After surgery, patients were instructed to take an analgesic (diclofenac sodium) every 8 hours and all eyes received artificial tears and flourometholone eye drop every four hours for 2 weeks, and chloramphenicol eye drop every 6 hours for 3 days. During the next two weeks, all patients were treated with flourometholone and artificial tears every 6 hours. These two eye drops were used every 8 and 12 hours during the second and third postoperative months, respectively, and were then discontinued. All patients were instructed to wear sunglasses in direct sunlight for 3 months.th and 14th days after surgery we measured the UCVA, BCVA, and the manifest, subjective, and cycloplegic refraction. At the 1st, 2nd, and 6th postoperative months, exams and measurements included UCVA, BCVA, manifest, subjective, and cycloplegic refraction, slit-lamp exams, applanation tonometry, ultrasonic pachymetry, keratometry, topography, and contrast sensitivity with and without glare. For evaluation of haze we used Hanna's grading scale from 0 (no haze) to 4+ . Contrast sensitivity was tested by Vector Vision CSV-1000 (Vector Vision, Dayton, OH) in spatial frequencies of 6 (B) and 12 (C) cycles per degree. [The preoperative visit included uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), manifest, subjective, and cycloplegic refractions, slit-lamp exams, applanation tonometry, corneal topography, ultrasonic pachymetry, keratometry, indirect funduscopy, and contrast sensitivity with and without glare. UCVA and BCVA were tested with the Snellen chart. On the first seven days after surgery, all patients were examined with a slit lamp and the area of the epithelial defect was measured with its ruler to identify the time of complete reepithelialization. On the 7 degree.  The manu degree. Repeated measures analysis of variance was used to assess changes over time after surgery. For all statistical tests, the significance level was considered 0.05.rd and 6th months visits . The mean age was 29.3 years (range, 20 to 45 years). The mean preoperative SE was -7.08 D ± 1.11 (SD) (range, -9.88 to -5.00D). The mean preoperative corneal thickness was 488.6 μm ± 11.9 (SD). At the first, 3rd, and 6th month after surgery, the mean corneal thickness was 357 μm ± 30 (SD), 373 μm ± 27 (SD), and 380 μm ± 28 (SD), respectively. Thirty-three eyes (61.1 %) had a preoperative BCVA of 20/20 or better, and 51 eyes (94.4 %) had a BCVA of 20/25 or better. Complete reepithelialization was seen in no eye by the 2nd postoperative day but in all eyes by the 6th day. The epithelial defect had resolved in 53.7 % of the eyes by the 3rd day, and in 92.6 % by the 4th postoperative day.Of the 28 study group patients, 3 did not show up on the 3rd postoperative month, 33 eyes (68.7 %) were within ± 0.5 D of emmetropia (SE) and 43 eyes (89.6 %) within ± 1.00D (SE). At the 6th postoperative month 39 eyes (81.3 %) were within ± 0.5D of emmetropia and 45 eyes (93.7 %) within ± 1.00D. Figure Figure rd postoperative month 32 eyes (66.7 %) had a UCVA of 20/20 or better and 47 (97.7 %) of 20/40 or better. All eyes had a BCVA of 20/40 or better and there were no lost lines in BCVA. On the 6th month visit, 37 eyes (77.1 %) had a UCVA of 20/20 or better and 48 (100%) of 20/40 or better. All eyes had a UCVA of 20/40 or better. On the first month follow-up visit, 2 eyes (3.7%) had +0.5 haze, but all had 0 haze on the 3rd and 6th month visits.At the 3th postoperative month compared to preoperative data while in the spatial frequency of 12 CPD, it had increased over time after surgery (P < 0.001).Figure In our study, no complications such as eccentric ablation, delayed reepithelialization, persistent epithelial defect, or microbial keratitis have been observed.PRK in high myopia remains a challenge due to its complications of haze and regression reported in previous experiments, and also the success rate of LASIK in these patients.  Yet, LASThis study was carried out to evaluate the safety and efficacy of PRK along with a 2-minute application of mitomycin-C 0.02% (0.2 mg/ml) on the exposed stromal bed after ablation was performed. Mitomycin-C is an antimetabolite and antibiotic drug. It is mostly used systemically in cancer chemotherapy. It has been used in ophthalmology in cases of intraepithelial neoplasms of the cornea and conjunctiva, ocular pemphygoid, and following surgical treatment of glaucoma and pterygium. Mitomycin-C has cytotoxic effects through inhibiting DNA synthesis. The logic behind using mitomycin-C is that the topical application of the drug on the cornea can inhibit subepithelial fibrosis through preventing the proliferation of stromal keratocytes, while the main causes of regression and haze are overacitvity and proliferation of stromal keratocytes following laser ablation.  The effeNo immediate toxic effects such as conjunctival chemosis or any delay or irregularity in re-epithelialization were seen. In only one case, after primary reepithelialization a large epithelial defect was seen on the fourth day , which healed in three days by applying a bandage contact lens. No complications such as corneal edema, melting, and perforation were observed in follow-up visits up to six months. Therefore, the topical application of mitomycin-C of the aforementioned concentration and duration was safe in our series. Yet, a longer follow-up is required to assess the long-term complications of mitomycin-C, and its careful application is recommended before long-term complications can be ruled out.th month visit. In the report by Carones, patients had a hyperopic shift of +0.5D by the sixth month; this is while our patients had a myopic shift of 0.43D.According to our previous experiences, we planned a 5% under-correction compared to our usual nomogram for LASIK. As a result of this modification, patients were close to emmetropia with a low variability on their 6The UCVA at six months after surgery was 20/40 or better in 100% and 20/20 or better in 77.1% of patients. The refractive and visual results of this study are much better compared to reports concerning the same amount of correction with LASIK, ,26 PRK, Considering the fact that haze influences BCVA, patients' BCVA is of great importance. In this study, no eyes lost any lines of BCVA by six months after surgery compared to the preoperative BCVA. None of the eyes had any grade of haze 3 or 6 months after surgery, which shows the efficacy of prophylactic application of mitomycin-C in preventing haze following PRK for patients with myopia over -5.00D. In addition, an average postoperative improvement in contrast sensitivity of 1.5 lines points to the safety and efficacy of the procedure in the quality of vision.In conclusion, using mitomycin-C in PRK for myopia greater than -5.00D seems safe and effective, and can reduce haze formation after surgery; therefore it can be considered a suitable alternative for patients with myopia greater than -5.00 D whose corneas lack an appropriate thickness to perform LASIK with a desirable optical zone. With this method, vision can be corrected with a better quality of vision regarding contrast sensitivity.None declared.HH, SMRT, AF and AK participated in the design of the study and the preparation of the manuscript. HH carried out all operations. SMRT visited patients in the follow up visits. AF and AK participated in the statistical analysis of the study. All authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Elevated pregnancy estrogen levels are associated with increased risk of developing breast cancer in mothers. We studied whether pregnancy weight gain that has been linked to high circulating estrogen levels, affects a mother's breast cancer risk.Our cohort consisted of women who were pregnant between 1954–1963 in Helsinki, Finland, 2,089 of which were eligible for the study. Pregnancy data were collected from patient records of maternity centers. 123 subsequent breast cancer cases were identified through a record linkage to the Finnish Cancer Registry, and the mean age at diagnosis was 56 years (range 35 – 74). A sample of 979 women (123 cases, 856 controls) from the cohort was linked to the Hospital Inpatient Registry to obtain information on the women's stay in hospitals.Mothers in the upper tertile of pregnancy weight gain (>15 kg) had a 1.62-fold (95% CI 1.03–2.53) higher breast cancer risk than mothers who gained the recommended amount (the middle tertile, mean: 12.9 kg, range 11–15 kg), after adjusting for mother's age at menarche, age at first birth, age at index pregnancy, parity at the index birth, and body mass index (BMI) before the index pregnancy. In a separate nested case-control study (n = 65 cases and 431 controls), adjustment for BMI at the time of breast cancer diagnosis did not modify the findings.Our study suggests that high pregnancy weight gain increases later breast cancer risk, independently from body weight at the time of diagnosis. Sensitivity of the breast to hormones and environmental exposures varies throughout a woman's life span . During Women whose pregnancy estrogen levels are elevated are at an increased risk of breast cancer. For example, women who took the synthetic estrogen diethylstilbestrol (DES) during pregnancy are at an increased risk of developing breast cancer , as are Adipose tissue aromatizes androgens to estrogens, and thus high body mass index (BMI) is linked to elevated estrogen levels in postmenopausal women . Some stThe study population was a historic cohort of women pregnant between 1954 and 1963 in Helsinki, Finland (n = 4,090). The cohort was a sample gathered for a study on hormone exposure, including 2,022 exposed, 2,062 controls and 6 women with unknown hormone exposure status. Information on the cohort was collected from the maternity cards of municipal maternity centers, which are used by most pregnant Finnish women. The hormone-exposed women had been prescribed estrogen or progestin drugs during pregnancy to prevent early abortion or preterm delivery. For each exposed woman, a woman next in the maternity center file who gave birth during the same year and had not been prescribed hormones during pregnancy, was chosen as a control. The cohort has been previously prescribed in detail . There wCancer cases were identified through a record linkage to the national cancer registry until June 2001. Mortality and emigration data were obtained from the population registry until August 2001. The linkage between the cohort and the registries was based on a unique personal identification number.th gestation weeks, the time between the body weight measurements 3–300 days, and delivery between 22–45th gestation weeks. For each mother, the gestation week she gave birth was determined by using the date of estimated timing of delivery. Women who did not fulfill these criteria were excluded  and 15–40th gestation weeks (Line B) for each mother. Weight gain was extrapolated to continue until 40th gestation week for all mothers, although 22.2% of mothers delivered at 39th gestation week or before.Pregnancy weight gain was first calculated as the difference between the first and last visit to maternity center. However, this window varied considerably among included mothers (range 3–295 days). The time-period of calculated weight gain was therefore adjusted by extrapolating a line for each mother to reflect her weight increase during pregnancy. The calculations are described in detail in Additional File th gestation week, the last weight measurement was before 30th gestation week, or information on pre-pregnancy weight, weight at the first or the last visit, or timing of the visits was not available. As indicated above, these subjects were excluded from the analyses.For mothers for whom both Line A (n = 2,143) and Line B (n = 2,184) were available, total pregnancy weight gain was calculated by adding the extrapolated weight gains from both periods. Thus, total pregnancy weight gain could be extrapolated only for 2,089 women. Cases and controls (66.5% vs 65.0%) did not differ concerning the number of available weight measurements. For the rest of the women, either the first weight measurement was later than 242 vs. 21.8 kg/m2, p < 0.001), older at first birth (25.2 years vs. 24.7 years, p = 0.016), had more children during index pregnancy (1.92 vs. 1.81 at index birth, p < 0.001), and were more often exposed to estrogen or progestin drugs (50.3% vs. 48.6%, p = 0.021). Their children were shorter (mean 49.3 cm vs. 50.3 cm, p < 0.001) and weighed less (mean 3,310 g vs. 3,472 g, p < 0.001), suggesting that excluded mothers' pregnancy weight gain might have been lower. It is probable that exclusion of these women had no major effect on the findings.We compared the characteristics of the mothers who were excluded (n = 2,001) to the characteristics of the mothers in the final study population for whom total pregnancy weight gain could be determined (n = 2,089). The two groups were similar in regard to breast cancer incidence, age at menarche, height and the frequency of visits to a private doctor. However, the excluded mothers were older (mean: 27.1 years vs. 26.5 years, p < 0.001), heavier  that included all breast cancer cases with data on pregnancy weight gain (n = 123). For each case, we chose seven randomly selected controls (n = 856) who were born in the same year as the case. These 979 women were linked to the Hospital Inpatient Registry to obtain information on the women's stays in hospitals. 117 cases were identified with a hospital visit in average 0.4 months after breast cancer diagnosis (median 0.0, range from -16.3 to 17.2), and of these cases information on body weight and height was available for 65 (53% of 123 cases). Among the controls, 699 had been a patient in a hospital at a similar age than their respective cases (maximum difference +/-5 years), and 431 of them had weight and height available in the hospital archives (50% of 856 controls, 6.6 controls/case).The breast cancer cases with no information on later body weight did not differ from the cases used for the nested case-control analysis. The controls with no information on later body weight were approximately 1.5 years older at the time of the hospital visit than the controls included to the study (p = 0.027).2-test for proportions. The incidence of breast cancer per 100,000 person years was counted by groups of 5 kg pregnancy weight gain, tertiles of pregnancy weight gain and tertiles of postpartum weight retention. Person years were calculated from the delivery to the diagnosis of breast cancer or other endpoint including death, emigration or end of the study.Statistical significance of possible differences in baseline characteristics of the study population, pregnancy weight gain and postpartum weight loss and weight retention by tertiles of pregnancy weight gain was tested by using analysis of variance for continuous variables and χThe association between pregnancy weight gain and breast cancer risk was further examined using a Cox regression model. Total pregnancy weight gain was included as a categorical covariate (tertiles) in the model. Age at menarche, age at first birth, age at index pregnancy, BMI before pregnancy, and parity (at index birth) were all used as continuous covariates in the model. Postpartum weight retention 51 days after delivery (mean) was later added to the model.The incidence of breast cancer was counted and the Cox regression model was carried out also separately for pre- and postmenopausal breast cancers. Information on the age at menopause was not available. Therefore all women were expected to have menopause at the age of 50 years.In the case-control study, weight and BMI change between pre-pregnancy and at the time of later hospital visit were compared between the tertiles of pregnancy weight gain . A Cox regression model that included later BMI was also used to analyze the data.In the cohort, 123 (5.9%) women developed breast cancer during the mean follow-up of 38.9 years. The mean age at diagnosis was 56.0 years (range 35–74). Background characteristics and index pregnancies are described by tertiles of pregnancy weight gain in Table Weight development during and after pregnancy is presented by tertiles of pregnancy weight gain in Table 2 and the mean total extrapolated weight gain during pregnancy was 13.3 kg (range -5.0–33.1 kg) in our cohort. Average pregnancy weight gain (and range) was 13.1 kg (-3.0–33.1) among primiparas, 13.5 kg (1.9–30.7) among women who gave birth to their second child and 13.2 kg (-5.0–32.4) among women who gave birth to at least their third child. The incidence of breast cancer by 5 kg categories of total pregnancy weight gain is shown in Table The mean BMI before pregnancy was 21.8 kg/m -5.0–32. among woth gestation week, results were similar than in the whole cohort (results not shown).All analyses were initially carried out separately for pre- and postmenopausal breast cancers. The results for postmenopausal women were similar to the results for the whole cohort (results not shown). The incidence of premenopausal breast cancer was too low for statistical analysis and pre- and postmenopausal breast cancers were not separated further in the analyses. When these analyses were restricted to mothers who delivered after 39th gestation weeks) and later pregnancy weight gain (15–40th gestation weeks). Early pregnancy weight gain was not associated with breast cancer risk. The impact of later pregnancy weight gain was similar to the impact of total weight gain, but more modest (results not shown).The incidence of breast cancer was calculated separately for early . The results did not either change when adjusted additionally for the year of index birth. The increased breast cancer risk in the highest tertile of pregnancy weight gain was found only for postmenopausal breast cancer . The RR for premenopausal cancer was 1.00 (95% CI 0.40– 2.48, p = 0.99). However, the number of premenopausal breast cancer cases with the information on all variables in the model was too low (n = 25) to yield sufficient power.No statistically significant differences in breast cancer risk were observed between the tertiles of postpartum weight retention, determined approximately 51 days after delivery Table .Later age at menarche was marginally related to a decreased risk of breast cancer (adjusted RR = 0.99, 95% CI 0.97–1.00). Mother's age at the time of first pregnancy or at the index pregnancy, parity at index birth or BMI before pregnancy were not statistically significantly associated with the risk of breast cancer. The results were similar when height and weight were used as separate variables in the model, instead of BMI.Lower pre-pregnancy BMI was associated with higher weight gain during pregnancy (p < 0.001) and higher postpartum weight retention (p = 0.003), but not with postpartum weight loss. The differences in the incidence of breast cancer were not statistically significant between the pre-pregnancy BMI-categories.Women who gained at least 15 kg weight during pregnancy had a higher BMI at the time of later hospital visit (29 years after pregnancy in average) than women who gained <11 kg weight during pregnancy (p = 0.021) . In the Cox regression model, women's later BMI at the time of diagnoses was not associated with breast cancer risk (adjusted RR = 0.96, 95% CI 0.90–1.04). Further, results relating to pregnancy weight gain and breast cancer risk were not altered by adding data on later BMI to the model (Table The results obtained in our study indicate that higher than recommended pregnancy weight gain increased mothers' risk of developing breast cancer. Thus, women who gained more than 15 kg during pregnancy had a 62% increase in breast cancer risk, compared to those who gained between 11–15 kg. The Institute of Medicine (IOM) published their most recent recommendations for pregnancy weight gain in 1990 . The recAn increase in breast cancer risk was seen mostly in women who were diagnosed with this disease after age 50 and thus were postmenopausal. However, the number of premenopausal breast cancers was low in the cohort, and we cannot exclude the possibility that pregnancy weight gain may also increase the risk of premenopausal breast cancer.Data generated in epidemiological studies rarely provide causal relationships. We propose four different mechanisms that may link high pregnancy weight gain to a later increase in breast cancer risk. First, weight retention in women who gained excessive amounts of weight during pregnancy may have persisted into their postmenopausal years. Women prone to postpartum weight retention might also be prone to long-lasting weight gain after pregnancy , and higAnother alternative is that women who gained an excessive amount of weight during pregnancy may have had higher pregnancy hormone and growth factor levels than women who gained within the recommended range, stimulating the growth of existing malignant cells in the breast, leading to development of a detectable tumor. Several studies have shown that markers of high pregnancy estrogen levels increase mother's breast cancer risk ,9-12,16.It is known that high hormone levels increase the proliferation of normal breast cells that then is accompanied by increased genomic instability and accumulation of DNA adducts ,32. ThusFinally, known and unknown causes of breast cancer may have confounded the results. For example, these causative factors might be more common in women who gain excessive amounts of weight during pregnancy or they caused women to gain excessive amounts of weight during pregnancy. A theoretical example is a gene mutation/polymorphism that could both make a woman more prone to gain weight during pregnancy and increases breast cancer risk.Methodological limitations have to be considered when interpreting the results, and they include high rate of exclusion and an exposure to estrogenic drugs during pregnancy. Of the 4,090 women available for the study, 48.9 % were excluded for reasons listed in Figure Some women in our cohort had been exposed to synthetic estrogens during pregnancy to avoid a threatening miscarriage, and this exposure might have affected the results. However, it was the initial reason for obtaining information from pregnant women, and we found no effect of the drug exposure on the incidence of breast cancer. We are not aware of any other cohort that could be used to assess the link between pregnancy weight gain and breast cancer risk, but if such a cohort becomes available, and it is not potentially compromised by high rate of exclusion of subjects or an exposure to drugs during pregnancy, the present results can be either confirmed or nullified. Follow-up of "old" cohorts similar to ours is rarely possible, making our study relatively unique.Another area of potential source for errors is the variability in time period between the weight measurements during pregnancy (range 3–295 days), requiring us to extrapolate the pregnancy weight gain for each woman. This step also has been successfully used in other studies . A furthFinally, in the case-control study that determined the impact of body weight at the time of diagnosis on breast cancer risk, information on this weight was obtained only for 53% of the cases and 50% of the controls. However, the direction of bias rising from exclusion may have diluted the effect, rather than caused it.In conclusion, our findings suggest that excessive pregnancy weight gain increased later risk of developing breast cancer. This association needs to be further confirmed in prospective studies.diethylstilbestrol – DES; body mass index – BMIThe author(s) declare that they have no competing interests.TK: PhD student who collected and put together all the material for the study, managed the data and did statistical analysis, and participated in writing the manuscript.MG: Participated in statistical analysis of the data and writing the manuscript.EH: Collected the original data base of pregnant women and was in charge of linking the data base to cancer registry, participated in statistical analysis planning and writing the manuscript.RL: Generated the idea of testing the hypothesis in the Hemminki data base, and participated in all stages of the study and in writing the manuscript.LH-C: Generated the hypothesis, obtained funding for the study, and was in charge of writing the manuscript.The pre-publication history for this paper can be accessed here:Calculation of line a and line b for each mother.Click here for file


Anopheles funestus and Anopheles arabiensis in Madagascar and, thus, there is need to further evaluate this trap in diverse epidemiological settings. This study reports a field evaluation of the Mbita trap in a rice irrigation scheme in KenyaMosquitoes sampling is an important component in malaria control. However, most of the methods used have several shortcomings and hence there is a need to develop and calibrate new methods. The Mbita trap for capturing host-seeking mosquitoes was recently developed and successfully tested in Kenya. However, the Mbita trap is less effective at catching outdoor-biting The mosquito sampling efficiency of the Mbita trap was compared to that of the CDC light trap and the human landing catch in western Kenya. Data was analysed by Bayesian regression of linear and non-linear models.An. arabiensis, An. funestus, and culicine species caught in the human landing collections respectively. There was consistency in sampling proportionality between the Mbita trap and the human landing catch for both An. arabiensis and the culicine species. For An. funestus, the Mbita trap portrayed some density-dependent sampling efficiency that suggested lowered sampling efficiency of human landing catch at low densities. The CDC light trap caught about 60%, 120%, and 552% of the number of An. arabiensis, An. funestus, and culicine species caught in the human landing collections respectively. There was consistency in the sampling proportionality between the CDC light trap and the human landing catch for both An. arabiensis and An. funestus, whereas for the culicines, there was no simple relationship between the two methods.The Mbita trap caught about 17%, 60%, and 20% of the number of The Mbita trap is less sensitive than either the human landing catch or the CDC light trap. However, for a given investment of time and money, it is likely to catch more mosquitoes over a longer (and hence more representative) period. This trap can therefore be recommended for use by community members for passive mosquito surveillance. Nonetheless, there is still a need to develop new sampling methods for some epidemiological settings. The human landing catch should be maintained as the standard reference method for use in calibrating new methods for sampling the human biting population of mosquitoes. Anopheles gambiae colony originating from southern Tanzania [An. gambiae, Anopheles arabiensis and Anopheles funestus in Western Kenya [An. funestus and An. arabiensis in rice-growing communities in the highlands of Madagascar [An. arabiensis An. funestus and culicines species of mosquitoes in a rice-growing community in western Kenya with relatively high mosquito densities is reported.Mosquito sampling is a prerequisite to most vector population studies . The entTanzania  and provrn Kenya ,7. In shdagascar ,7. In thAn. arabiensis and An. funestus [These studies were carried out in a village adjacent to the Ahero rice irrigation scheme in western Kenya. Populations of funestus  as well funestus  are predfunestus ,9.In Ahero, three houses were selected upon receiving consent from the household heads. Occupants were given a non-impregnated bed net per sleeping space and trained in their correct use. With informed consent, three young men who had earlier been trained in mosquito sampling  were rec®). A follow-up was made to ensure that any parasitaemia was fully cleared. If parasitaemia did not clear, the participants were referred to hospital for further treatment with second line drugs. The Kenya Medical Research Institute (KEMRI) through the KEMRI/National Ethical Review Committee granted ethical approval (KEMRI/7/3/1) for this study.Informed consent was obtained from all the participants. Thick and thin blood smears were regularly taken from the participants to examine for the presence of malaria parasites and, when found positive, they were treated with pyrimethamine-sulfadoxine  = αtβcE(xi)E(yi) is the expected number of mosquitoes caught using the method being tested; E(xi is the expected number of mosquitoes caught using the human landing method (assuming the same mosquito collector as bait); αt is a multiplication factor corresponding to trapping method t in relation to the reference trapping method which was human landing catch; and βc is a multiplication factor corresponding to human bait c compared to the reference catcher, assigned number 1, whose value is set to 1.Where: E(yi) = αtβc(E(Xi))ytyt which is the exponent corresponding to trapping method t. A value of yt different from 1 indicates a lack of proportionality between the methods. Both models assumed Poisson errors in the numbers of mosquitoes caught by any of the three methods.All the terms for model B are identical to model A except that it includes An. arabiensis and 309, 427, and 470 An. funestus respectively. The corresponding figures for culicines mosquitoes (mainly Culex species) were 32, 121 and 578. Also, 30 male mosquitoes were caught, 29 of them by the CDC light trap and one in the landing collections. The parameter estimates from our models (Table An. arabiensis, An. funestus, and culicine species caught in the human landing collections respectively. There was consistency in the sampling proportionality between the Mbita trap and the human landing catch for both An. arabiensis and the culicine species whereas for An. funestus, the Mbita trap portrayed some density-dependent sampling efficiency. More specifically, the Mbita trap appears more sensitive than human landing catch at low mosquito densities. The CDC light trap, on the other hand, caught about 60%, 120%, and 552% of the number of An. arabiensis, An. funestus, and culicine species caught in the human landing collections respectively. There was consistency in the sampling proportionality between the CDC light trap and the human landing catch for both An. arabiensis and An. funestus, whereas for the culicines, there was no simple relationship between the CDC light trap catches and the landing catches (Table An. gambiae s.l. were found to be An. arabiensis.Overall, the Mbita trap, the human landing collection and the CDC light trap-bednet method caught 135, 576, and 474 An. arabiensis compared to their reported performance for nearby An. gambiae s.l. population that comprised of roughly equal numbers of An gambiae sensu stricto and An. arabiensis [An. arabiensis, a mosquito species that is usually largely zoophagic but endophilic [An. arabiensis to seek alternative hosts outdoors. For the case of the human landing collection, the human bait was more readily available for such indoor resting mosquitoes.The results obtained from this study indicate a three-fold decrease in efficiency for both the Mbita trap and the CDC light trap when used to sample abiensis . Howeverdophilic . TherefoAn. arabiensis in the highlands of Madagascar [An. arabiensis as this study found but with no correlation between the two methods.Second, unlike in Lwanda , where ndagascar . Other sdagascar  for An. An. funestus in Ahero was similar to that reported for Lwanda [An. funestus was about 2.5-fold that in Lwanda. The relatively high densities of this species in Ahero compared to Lwanda, might, at least partly, account for these observations. At Lwanda, where the densities of An. funestus were low, no density-dependent sampling efficiency was noted for the Mbita trap while some density-dependent sampling efficiency was noted for the CDC light trap [The performance of the Mbita trap relative to the human catch for r Lwanda ,7 but shght trap  suggestiMany studies have evaluated the performance of the CDC light trap relative to the human landing catch but it is very difficult to compare the results due to the different methodologies and sampling procedures applied. In this study, the three methods were used concurrently in different houses on the same night while in other studies ,18,19 thAlthough the Mbita trap is less sensitive than either the human landing collections or the CDC light trap, for a given investment of time and money , it is lEMM designed the trap, designed the study and drafted the manuscript. GOM & DOO supervised the fieldwork and recorded the data. LWI & PNN were involved in the study design and drafting the manuscript, TAS carried out the data analysis and helped in the interpretation of results. GFK guided the experimental design, data analysis and drafting of manuscript. BGJK conceived the initial idea of developing the trap and solicited for funds used in the trap development and trials. All authors read and approved the final manuscript.


This study aimed to ask a sample of the general population about their preferences regarding doctors holding discretionary powers in relation to disclosing cancer diagnosis and prognosis.The researchers mailed 443 questionnaires to registered voters in a ward of Tokyo which had a socio-demographic profile similar to greater Tokyo's average and received 246 responses (response rate 55.5%). We describe and analysed respondents' attitudes toward doctors and family members holding discretionary powers in relation to cancer diagnoses disclose.Amongst respondents who wanted full disclosure about the diagnosis without delay, 117 (69.6 %) respondents agreed to follow the doctor's discretion, whilst 111 (66.1 %) respondents agreed to follow the family member's decision. For respondents who preferred to have the diagnosis and prognosis withheld, 59 (26.5 %) agreed to follow the doctor's decision, and 79 (35.3 %) of respondents agreed with following family member's wishes.The greater proportion of respondents wants or permits disclosure of cancer diagnosis and prognosis. In patients who reveal negative attitudes toward being given a cancer disclosure directly, alternative options exist such as telling the family ahead of the patient or having a discussion of the cancer diagnosis with the patient together with the family. It is recommended that health professionals become more aware about the need to provide patients with their cancer diagnosis and prognosis in a variety of ways. Cancer ranks as the third leading cause of death worldwide, accounting for approximately 12 % of all recorded deaths -6, and tIn Japan, historically, physicians have withheld discussing cancer diagnoses directly with patients . HoweverIn Japan, the patient, family and doctor are the main players in cancer disclosure. According to legal precedents in Japan, doctors are given a wide range of discretionary powers regarding disclosure -16. As aThis study was a cross-sectional, stratified random sampling survey of the general population in their 40s to 50s. As people over 60 years old are epidemiologically more at risk of having cancer, we excluded them not only because it seemed harmful to ask about these experiences, but also because there was a possibility that their responses would be affected by their experiences. Participants were selected from eligible voters in 'A' ward in the Tokyo Metropolitan Area. We chose 'A' ward as a representative area of Tokyo because various social indices such as the proportion of the elderly population, average length of education, and population growth rate were consistent with the Tokyo average . The resThe questionnaire was developed in consultation with 6 medical staff and 19 patients. The questionnaire presented a hypothetical scenario in which "The doctor discovers terminal cancer, but the patient does not know yet." to each respondent, and asked about preferences regarding diagnosis and prognosis disclosure; "How would you want to be told, if you were in such a situation". Answer choices for disclosure preferences regarding diagnosis were: 1."I would not want to be given any information regarding my diagnosis [non-disclosure]", 2. "I would like to obtain information regarding my diagnosis of a general nature but not in detail" 3." "I would like to be given all information regarding my diagnosis [full-disclosure]". Choices for disclosure on the prospects of complete recovery (CR) and expected length of survival (LS) were: 1. "I would not want to be given any information about the prospects of CR and LS [non-disclosure]", 2." I would like to obtain information on the prospects of CR and LS of a general nature but not in detail. [partial-disclosure]", 3. "I would like to be told about my prospects of CR and LS eventually. However, I would like to receive only general information on the prospects of CR (LS) when I am initially informed about the disease [postponed full-disclosure]", and 4. "I would like to be told about my prospects of CR and LS without delay. [immediate full-disclosure]". The reason for providing s answers allowing partial-disclosure was based on research by Akabayashi which inRespondents were asked about their attitudes toward doctors and family members holding discretionary powers regarding cancer diagnosis disclosure. In order to compare the attitudes and characteristics of respondents who preferred immediate diagnosis and prognosis and those who did not, analysis was carried out twice. In the first analysis we included respondents who did not choose "full diagnosis and prognosis without delay", and we included the data from the remaining respondents that explained the reason for allowing to receive immediate diagnosis and prognosis. In the second analysis we included respondents who did want to receive diagnosis and prognosis, and we included data from the rest of the respondents about their reasons for preferring the withholding of diagnosis and prognosis. We also asked about preferences regarding the cancer disclosure process, such as whether people would like to obtain information ahead of their family.The questionnaire also included the trait part of the Japanese version of the State-Trait Anxiety Inventory (STAI), which assesses the personality predisposition to anxiety -29. The Firstly, we calculated all respondents' disclosure preferences regarding diagnosis, CR and LS. Secondly, we calculated the attitudes toward doctors and family members holding prognosis discretion of respondents who preferred to be given diagnosis information directly, and those who did not. Wilcoxon's test was used to examine the differences between the attitudes held toward doctors and family members holding discretionary powers between these two groups. Statistical analyses were conducted using SPSS Version 11.5J.The socio-demographic characteristics of the respondents are shown in Table Respondents' preferences regarding diagnosis and prognosis disclosure are shown in Table Regarding the contextual reason for wanting to receive full diagnosis and prognosis information without delay, 117 (69.6 %) respondents agreed to follow the doctor's initiative and 111 (66.1 %) of the respondents agreed to follow the with family member's decision Figure . WilcoxoRegarding the cancer disclosure process, more than half the respondents  answered that they would like to obtain diagnosis and prognosis information ahead of their family, a third (N = 82: 32.3 %) answering that would like to receive information with their family together at the same time. Only 26 (32.3%) respondents preferred to obtain this information after the doctor had already informed their family.Regarding preferences relating to diagnosis and prognosis, only 2.7 % of the respondents wanted no information regarding a cancer diagnosis. In addition to considering to tell or not to tell, the extent to which physicians should inform patient of diagnosis and prognosis poses a difficult decision in clinical settings. However, more than two-thirds (68.7 %) wanted full diagnostic and general prognostic information in a general nature but not in detail or wanted to be told about their prognosis eventually. Less than a third (28.9 %) wanted full information regarding diagnosis and prognosis without delay. These results suggest that a disclosure policy which provides patients with full information on diagnosis and general information on prognosis can satisfy the majority of patients' preferences. The results also suggest that any disclosure policy should also try to acknowledge and meet patients' wishes of being informed together with their families, and of being given information at a later time.Nevertheless, some patients do not want any information regarding their cancer diagnosis. In the clinical setting, medical staff needs to develop policy and procedures that can deal with the needs of patients who do not want any information as well as those patients and who want complete information immediately. The priority in identifying these types of patients over-rides other factors which affect patients preferences regarding diagnosis and prognosis such as patient characteristics and seriousness of cancer (previous research conducted by the authors ). RegardDespite the data that indicates a mix of patients' preferences regarding cancer diagnosis, it may not be necessary for doctors to make choices regarding diagnosis by actually knowing individual patients' preferences. As opposed to those who would prefer no information, a greater proportion of respondents wanted to receive full information, even contrary to their preferences. Two other surveys with the general public show a similar tendency of patients wanting more information regarding cancer diagnosis than they used to. Asahi Newspaper found that regarding one's own cancer diagnosis and prognosis, in 1989, 59% of respondents wanted disclosure, which increased to 76%) in 2000 . SimilarTo simulate the fact that cancer results in a variety of disease outcomes for patients, we used scenarios with a range of severities in the outcomes of the cancer. As a result, there is little difference between respondents who had experienced cancer disclosure as a patient and those who did not, and the diagnosis preferences revealed in this study (full-disclosure, 85.4%) are consistent with previous studies (Seo , 85.7%: This study has several limitations. Although the response rate to this study was moderate for a general population survey, we acknowledge that the characteristics of the respondents might not be wholly representative of the general population. Also, because we restricted participants to adult inhabitants in an urban area in Japan, further research is required to test the validity of these findings.It is recommended that health professionals become more aware about the need to provide patients with options to be given their cancer diagnosis and prognosis in a variety of ways. The greater proportion of respondents wants or permits disclosure of cancer diagnosis and prognosis. However, in patients who reveal negative attitudes toward being given a cancer disclosure directly, alternative options should be made available such as telling the family ahead of the patient or having a discussion of the cancer diagnosis with the patient together with the family. Further research with people aged over-sixty is needed to test the applicability of these findings to older age groups.Although partial funding for this study was provided by the Education Ministry within the Japanese government, the views and opinions expressed in this report are those of the authors and not those of the funding organisation.HM planned and conducted the survey, carried out the analysis, and wrote this paper.HT, MT, TS and IK made close supervision and extensive support. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Shorter time to treatment is associated with lower mortality in acute coronary syndromes (ACS). A previous (1994) survey showed substantial delays for acute myocardial infarction (AMI) in Ireland. The present study compared current practice with 1994 and surveyed acute coronary syndromes as a more complete contemporary evaluation of critical cardiac care than assessing AMI alone.Following ethics committee approval, all centres (N = 39) admitting acute cardiac patients to intensive/coronary care unit provided information on 1365 episodes. A cross-sectional survey design was employed.Since 1994, median hospital arrival to thrombolysis time was reduced by 41% (76 to 45 minutes). Thrombolysis was delivered more often in the emergency department in 2003 (48% vs 2%). Thrombolysis when delivered in the emergency department was achieved faster than thrombolysis delivered in intensive/coronary care . Suspected AMI patients who did not subsequently receive thrombolysis took longer to present to hospital  and had longer transfer times to the intensive/coronary care unit following arrival . Fewer confirmed AMI cases received thrombolysis in 2003 (43% vs 58%). There was an increase in confirmed cases of AMI from 1994 (70% to 87%).Substantial improvements in time to thrombolysis have occurred since 1994, probably relating to treatment provision in emergency departments. Patient delay pre-hospital is still the principal impediment to effective treatment of ACS. A recent change of definition of AMI may have precluded an exact comparison between 1994 and 2003 data. Ireland has one of the highest mortality rates from cardiovascular disease in the European Union . Acute cInternational guidelines, for example those from the European Society of Cardiology ,9 and thSince 1994, there has been no examination of time to treatment and the extent to which international guidelines for treatment of AMI are being achieved in Ireland. This study assessed the presentation and management of a national cohort of suspected ACS patients admitted to intensive/coronary care units (I/CCUs) in all 39 Republic of Ireland hospitals providing such care. We decided to extend the range of patients assessed from those with suspected AMI (as was the case in previous surveys ,18) to aAll Irish centres admitting suspected ACS patients to I/CCU (N = 39) agreed to participate following relevant ethics approval . Data co2 was used for categorical variables, and t-tests were used for continuous variables. Results from 1994 are reported, but significance tests were not conducted between 1994 and 2003 data (as raw data from 1994 was unavailable). Total time to treatment was defined as follows: symptom onset to reperfusion (thrombolysis or direct infarct angioplasty). Inpatient and other hospital transfer times were not included in the analysis for 1994 or 2003 samples.Analysis was conducted on the data using STATA/SE 8.0. Mann-Whitney U tests were used to test for significance between treatment times, χThe sample consisted of 1365 episodes, 935 suspected AMI and 430 suspected other ACS patients. The gender breakdown has been described elsewhere (manuscript submitted for publication). The overall mean age was 64 years . Admission characteristics are shown in table The demographic profile of patients admitted for suspected AMI in 2003 appears similar to those admitted in 1994. Other ACS patients differed from suspected AMI patients in 2003 in the following aspects: they were younger, less likely to be admitted by ambulance, more likely to drive themselves to hospital, and had a higher prevalence of previous ACS and coronary interventions.Both location of, and speed of administration of thrombolysis have changed considerably in a positive direction since 1994  than I/CCU administered thrombolysis (median 60 minutes) in 2003 (z = 5.62, p < .0001).In 2003, 29% of those thrombolysed were treated within 90 minutes of calling for professional help. This rose to 42% and 62% within 2 and 3 hours respectively. On hospital arrival, 35% of patients were thrombolysed within 30 minutes, rising to 60% and 74% within 60 and 90 minutes respectively. Thirty-six per cent of hospitals thrombolysed 80% or more of patients in the emergency department while 56% of hospitals thrombolysed over 50% of patients in the emergency department.Suspected AMI patients waited a similar length of time to get to hospital from onset of symptoms in 2003 as 1994 (Table Patients waited longer to be admitted to I/CCU in 2003, but received thrombolysis more quickly (45 mins v 76 mins) after hospital arrival. This represents a 41% decrease in time-to-thrombolysis since 1994. In 2003, total time to treatment for suspected AMI patients who received reperfusion was 4 hours 00 mins.Patients with suspected AMI who were subsequently thrombolysed (thrombolysed AMIs) presented to hospital (2 h 34 mins vs 5 h, z = 7.33, p < 0.0001) and had a faster I/CCU transfer time (1 h 10 mins vs 2 h 17 mins, z = 8.92, p < 0.0001) than suspected AMI patients who were not thrombolysed (non-thrombolysed AMIs). Suspected other ACS patients also waited significantly longer than non-thrombolysed AMIs for hospital transfer to I/CCU .In 1994, treatment times for patients referred by primary care physicians were significantly longer than those who self-referred . In 2003, primary care physician-referred suspected AMI patients also had a significantly longer pre-hospital delay (5 h vs 2 h 28 mins, z = 7.9, p < 0.001).For suspected AMI patients, a previous experience of AMI made no difference to hospital presentation time (3 h vs 3 h 45 mins, z = 1.2, p > 0.05). There were no gender differences in pre-hospital delay time (3 h 53 mins for men vs 3 h 14 mins for women, z = 0.63, p > 0.05), or hospital arrival to thrombolysis time (45 mins for men vs 50 mins for women, z = 1.43, p > 0.05) for suspected AMI patients in 2003.For suspected AMI patients, there was an increase in those patients diagnosed with myocardial infarction of 21% from 1994 to 2003, and a 10% reduction in the diagnosis of unstable angina  in time to thrombolysis from hospital admission has occurred since 1994. This can probably be attributed in large part to the relocation of thrombolytic administration to the emergency department, thereby reducing the 'door-to-needle' times in 2003. Similarly, treatment of AMI patients in emergency departments prior to transfer to I/CCU may account for longer I/CCU transfer times in 2003.Significant progress has been made in the treatment of AMI patients who receive thrombolysis, which has yielded faster 'door-to-needle' times. Suspected AMI patients who received thrombolysis in the 2003 sample were treated more quickly than 1994 (median 45 mins v 76 mins).The transfer of thrombolytic administration from the I/CCU (96% in 1994) to the emergency department (48% in 2003, with 48% administered in I/CCU) is probably the main reason for the decreased time to treatment for thrombolysed patients. The present survey found, for instance, that 56% of hospitals thrombolysed over half of their patients in the emergency department. It is not clear, however, that an additional shift of thrombolysis to the emergency department in the remaining hospitals would also result in a further reduction of 'door-to-needle' time. This is because some hospitals already adopt a 'fast-track' policy, where chest pain patients are admitted directly to CCU, bypassing emergency department assessment. Adopting a strategy of emergency department thrombolysis may have little or no effect in these cases.Nonetheless, only 35% of patients received thrombolysis within 30 mins of hospital arrival, which compares unfavourably to other surveys . These Substantial pre-hospital and in-hospital delays were seen for non-thrombolysed AMIs. Suspected AMI patients who did not receive thrombolysis waited significantly longer for transfer to I/CCU than those who received thrombolysis. Indeed, this group of AMIs had comparable times to patients with suspected other ACS. These patients presented to hospital more slowly than thrombolysed AMIs. This may indicate the less severe symptoms of unstable angina and non-ST-elevation myocardial infarction. Also, recent changes in AMI definition have lead to increases in proportions of diagnosed AMI patients and decreases in proportions of patients diagnosed with unstable angina -22. ThesSuspected AMI patients who did not receive thrombolysis took significantly longer from hospital arrival to arrive in I/CCU than did patients who received thrombolysis. Suspected other ACS patients presented to hospital in time frames similar to suspected AMI patients who did not receive thrombolysis, but were not admitted to I/CCU as quickly. The development of chest pain assessment units and other similar units , which involve the initial screening of chest pain patients to determine whether the pain is cardiac in origin prior to transfer to I/CCU, may have skewed the data in the current survey. A typical scenario may be that a patient currently arrives at hospital, without ST-elevation when assessed by ECG, and is assessed for some time in the chest pain assessment unit to either 'rule-in' or 'rule-out' ACS. In the past, such patients may have been admitted directly to I/CCU. In addition, these findings may reflect the triaging of patients in the emergency department, where patients labelled as suspected AMI were treated more quickly than those labelled as suspected other ACS. Patients can be triaged into groups reflecting the necessity for immediate treatment. Non-ST-elevation myocardial infarction and unstable angina patients may be detained for observation in the emergency department. It might also be that pressure for I/CCU bed places is more quickly resolved for the more acute ST-elevation AMI patients. However, further prospective observational research on this aspect of care is required.Patient delay prior to hospital arrival is still the biggest impediment to improving treatment times for AMI and other ACS. Patients who were referred by primary care physicians had a significantly longer time to treatment than those who self-referred in both 2003 and 1994. Clearly, in the present system, although substantial improvements have been made since the mid-1990s, a 'call-to-treatment' standard of 90 minutes is not currently being met. The present survey found that 29% of patients were thrombolysed within 90 minutes of calling for professional help. Future research and resources need to focus on a reduction in pre-hospital delay factors by the services and professional groups concerned. A number of psychological studies have provided detailed examination of patient contributions to delayed help-seeking for AMI -27. ThesAs regards reducing health services delay, one method is to authorise health professionals in the pre-hospital setting to administer thrombolysis. Ambulance personnel and primary care physicians are the two most obvious choices. The administration of thrombolysis by ambulance personnel has been shown to reduce time to treatment . A recenThe present study has highlighted the need for a national prospective registry of ACS. The value of such registries has been shown in other countries. For example, registries increase the use of appropriate reperfusion therapy, but to ensure this practice continues they need to be ongoing . In the Significant progress in some aspects (e.g. time to thrombolysis) of care for suspected ACS has occurred, but there is still scope for improvement. A necessary goal is to increase the proportions of patients seen within the recommended time. Other aspects of ACS care also now require attention. Patient delay pre-hospital should remain the main focus of future research. The implementation of a national registry would allow resources to be focused on these aspects and facilitate routine health care monitoring.The author(s) declare that they have no competing interests.FD carried out the survey, analysed the data and drafted the manuscript. HM, DD & ES conceived of the study and participated in its design and coordination. RC participated in the study design and coordination, and provided statistical input on data analysis and interpretation. All authors provided critical input on manuscript drafts, and approved the final version.The pre-publication history for this paper can be accessed here:


In Botswana, explicit color photos of people with AIDS have been used to spread knowledge, with the aim of saving lives Southern Africa poses special problems for AIDS educators and health care workers. Because there is a strong tradition of oral communication in the region, written educational materials often do not have as much impact as the spoken word. We have found that using colour images of HIV/AIDS in a workshop setting to provoke discussion can be a useful alternative to more conventional, written materials. In this article, we discuss our experience of using such images to raise community awareness about the AIDS epidemic in Botswana.http://www.talcuk.org/). The organisation has traditionally focused on developing countries, particularly sub-Saharan Africa and Asia. In recent years, TALC has become more global; it now distributes materials to more than 200 countries and sends educational materials on CD-ROM at no cost to health workers in developing nations.Teaching-aids At Low Cost (TALC) is a nongovernmental organisation that supplies cheap teaching aids and books to raise standards of health care and standards of living—especially in poverty-stricken areas—worldwide  and other sexually transmitted diseases, images that explained the basic virology and transmission of HIV , and imaShowing these pictures to local people was hugely controversial. For example, some elderly participants walked out when they saw the explicit pictures. Some community members approached local political counsellors to voice their concerns about a “decay of culture” and a “lack of respect”. Some parents did not want their children to see the images at all, because “they would corrupt their morals and young minds” and would encourage children to “experiment with sex”. As the team leader, I was fined chickens on several occasions by local chiefs and elders for the “crime” of showing these explicit TALC slides.The government gave our teaching project very little support in the early days; we were even cautioned by the highest authorities at the Ministry of Health. The Church, too, wanted nothing to do with our programme of “loose morals”.Despite these obstacles, over the next ten years we held over a hundred workshops, which eventually involved all government departments and levels of society in Botswana. Today, we are still using the same pictures. In 2000, the United Nations Development Programme declared Athlone Hospital's initiative as one of the “best practices” in Botswana Given the terrible impact that AIDS has had on the community, the same community members who once resisted our teaching project ask us angrily why doctors were not sufficiently aggressive in using pictures in the early days of AIDS. One telling statement made in a workshop was: “you doctors are to blame for what has happened to Africa, and particularly to our children. You should have done this ten years ago before one quarter of the population became infected. The blood of our children, who have died, rests on your heads”.info@talcuk.org (or mail TALC, P. O. Box 49, St. Albans, AL1 5TX, United Kingdom).In Botswana, I used a slide projector and occasionally a mobile electrical generator, but such equipment is not widely available in most African countries. As an alternative to using colour slides, TALC has developed a folded A4 (210 mm × 279 mm) sheet with 12 colour images as a way of presenting the important messages about HIV/AIDS. This leaflet is available on request; E-mail: In our experience, the slides or leaflet work best if you can get the participants to sit in small groups for discussion. Each group should have at least one set of pictures. In your introduction, mention that to talk about sex or death is not taboo in a world of AIDS. Encourage active participation by all.Show one picture at a time—”let the picture talk”—and do not initially look at the accompanying text. Ask the participants to describe what they see in English or in the vernacular. Encourage participants to work out for themselves what the message is in the picture. Discuss all the possible answers. Then look at the text that accompanies the picture. Provide an answer built from the participants' words. If appropriate, ask people about their own relevant experiences. Finally, ask the participants to pin the pictures to the wall, making sure that each picture is put up by a different participant. Revise the lessons learned at the end of the session. Revise again, weeks later, if possible. At the end of the day, the participants should be able to say, “we did it by ourselves”.The pictures show examples of how HIV/AIDS can affect people. They must not be thought of, or used, as a way to diagnose HIV/AIDS in participants or their relatives or friends. Emphasise to all participants that if they have any reason to suspect that they (or anyone they know) have HIV/ AIDS, they should attend a clinic where trained health workers can help them.For people in Botswana, “seeing is believing”. Written descriptions are often not enough; showing pictures of herpes zoster, syphilis ulcers, or tuberculosis lymphadenopathy can be a powerful teaching tool. Once the initial shock is overcome, these colour pictures offer a straightforward way to demonstrate the realities of the disease far and wide.