To identify all the records within the Brazilian Hospital Information System (HIS) that contained information suggestive of severe maternal morbidity (near miss); to describe the diagnoses and procedures used; to identify variables associated with maternal death.A descriptive population study with data from the HIS and Mortality Information System (MIS) files of records of women during pregnancy, delivery and in the postpartum period in all the capital cities of the Brazilian states in 2002. Initially, records of women between 10 and 49 years of age were selected; next, those records with at least one criterion suggestive of near miss were selected. For the linkage of HIS with MIS and HIS with itself, a blocking strategy consisting of three independent steps was established. In the data analysis, near miss ratios were calculated with corresponding 95% confidence interval and the diagnoses and procedures were described; a multiple logistic regression model was adjusted. Primary and secondary diagnoses and the requested and performed procedures during hospitalization were the main outcome measures.The overall maternal near miss ratio was 44.3/1,000 live births. Among the records indicating near miss, 154 maternal deaths were identified. The criteria of severity most frequently found were infection, preeclampsia and hemorrhage. Logistic regression analysis resulted in 12 variables, including four significant interactions.Although some limitations, the perspective of routinely using this information system for surveillance of near miss and implementing measures to avoid maternal death is promising. Maternal mortality has been the target of studies in the area of public health since the beginning of the last century, particularly in the developed world, where investigations have been carried out in this field over a longer period of time. The findings of these studies have led to changes that resulted in a significant reduction in the Maternal Mortality Ratio (MMR) of these countries , contrarThis would be especially worthwhile for developing countries. Mantel et al.  introducThe objectives of the present study were: to identify among all women admitted to hospital during pregnancy, delivery and in the postpartum period, in the 27 Brazilian capital cities in 2002, those that were indicative of severe acute maternal morbidity; to describe the diagnosis of the cause of hospitalization and the procedures carried out; to identify women who died according to the MIS, the HIS and the linkage between the two; and to identify the factors  associated to maternal death.This was a descriptive population study consisting of an analysis performed on hospital (HIS) and vital records (MIS). The sample size was calculated considering a near miss morbidity ratio of 11 events per 1,000 deliveries , with a The HIS-2002 and the MIS-2002 databases for each city for the year of 2002 were obtained especially for this study from the DATASUS and the Secretariat of Health Surveillance of the Ministry of Health. They contained information regarding the identification of women that enables a relationship to be established between databases. This study was approved by the Institutional Review Board of the School of Medical Sciences, University of Campinas , and follows the principles laid out in the Declaration of Helsinki. Confidentiality was guaranteed with respect to the non-identification of cases.The variables from the HIS used were: principal and secondary diagnoses, procedures requested and carried out, and total number of days in the ICU during hospitalization. First, the hospitalization records of women during pregnancy, delivery and in the postpartum period (diagnoses of group "O" of the ICD-10 and/or procedure beginning with 35 or 69), and with 10 to 49 years of age (reproductive age) were selected. Next, those records with at least one item suggestive of severe maternal morbidity (near miss) were selected. This second selection was based on a previously drawn-up list resulting from a search for key-words using the general criteria described by Mantel et al. [The main fields used to establish linkage were name and date of birth. The software used to establish probabilistic record linkage between the systems was the Reclink II . This frThe initial clerical revision of the junction HIS vs MIS occurred for the pairs whose agreement was not optimum (scores ≥ 10); the names were checked; if there was any doubt, the dates of birth were checked; if still necessary, the date of release from hospital according to the HIS was checked against the date of death according to the MIS. A complementary revision was also carried out for cases with lower agreement (scores between 5 and 10). A similar revision was carried out for the junction of HIS with itself .For data analysis, the Maternal Near Miss Ratios (MNMR) were initially obtained. Next, the number of maternal deaths was listed according to the process used to identify these deaths. After this, the diagnoses and procedures were described in the selected women. Finally, multiple logistic regression analysis  was carrFrom a total of 634,577 medical records in the HIS files concerning women during pregnancy, delivery or in the postpartum period, and with 10–49 years of age, 5.3% of this total were initially selected, corresponding to 33,797 women whose records contained at least one item suggestive of near miss. After subtracting the maternal deaths and multiple hospitalizations identified as referring to the same woman, 32,379 women were identified as presenting severe acute maternal morbidity. The overall maternal near miss ratio (MNMR) was therefore 44.3/1,000 liveborn infants  were found using the linkage of the HIS with the MIS, and 61% (48% plus 13%) from the "hospital charges" field of the HIS. Therefore, using the two procedures together, it was possible to identify 48% of these deaths Table .The descriptive analysis of diagnoses and procedures showed that the most frequent diagnostic criteria for maternal death were immunological disorders/severe sepsis with 20.8% of the cases, followed by severe preeclampsia (14.9%) and severe hemorrhage 14.3%). For the cases of near miss, the same main criteria of signs and symptoms applied: severe preeclampsia (30.6%), immunological disorder/severe sepsis (23.7%) and severe hemorrhage (20.3%). For the procedures, the corresponding percentages were, in general, lower and the item concerning admission to the ICU, in which diagnoses did not appear, was the most frequent criterion for maternal death, with 47.4% of 154 cases; however, it was the fourth most frequent criterion for describing cases of near miss , while the lowest probability (0.0015) was for the individual criterion of severe preeclampsia Table .The general results of the current study showed that overall maternal near miss ratio for the state's capitals in Brazil was 44.3/1,000 live births. Among the records classified as near miss, 154 maternal deaths were identified. The criteria of severity most frequently found were infection, preeclampsia and hemorrhage. They also allow having some probabilities of dying according to their combined occurrence, enhancing the perspective of using this routine information system for surveillance of near miss.There are various advantages to using information routinely collected by the HIS of the Brazilian National Health Service, among them the low cost and relatively short period of time between collection and the availability of the files for public use . NeverthIn the present study, some problems could be identified. Initially, the intention was to use the number of deliveries as the denominator to calculate the maternal near miss ratio. However, due to the fact that this figure could not be directly obtained from the database, the number of liveborn infants coming from the Information System on Liveborn Infants (SINASC), was considered instead. SINASC includes a subset of births occurring in private hospitals that are not part of the National Health System, which is not the case of the HIS. In addition, the total number of deliveries should be greater than the number of liveborn infants since the former includes stillborn infants. Therefore, it was necessary to use the number of liveborn infants for the calculation of the MNMR, which consequently resulted in the higher values obtained.The maternal near miss ratio in this study may be overestimated due to the limitation in the lower denominator that was used (number of liveborn infants instead of deliveries). On the other hand, it should be emphasized that the use of data deriving from the HIS is restricted to hospitalizations with details limited to two diagnoses and two procedures; therefore, the MNMR of 44/1,000 liveborn infants may be underestimated. From the set of cases selected, it was possible to note that the most frequent diagnoses and procedures found in cases of maternal death were also those identified in cases of near miss, i.e. infection, preeclampsia and hemorrhage.Another problem was detected when approximately half the maternal deaths declared in the MIS could not be found in the HIS, another aspect of this study that has already been reported . In the By classifying the women into two groups , the principal items of diagnoses and procedures were able to be described according to the tentative criteria suggested by Mantel et al., 1998 , by WateIn the final logistic regression analysis, it was possible to calculate an equation for estimating the probability of dying. Considering the three groups of criteria, referred to as management complexity, organic dysfunction and signs and symptoms ,8, the pThe probabilities calculated here highlight some problems that merit particular vigilance, such as hospitalization in the ICU in association with infection, emergency hysterectomy with severe hemorrhage, and cerebral disorder, among others. Despite the limitations that exist in the HIS, the prospect of using this data source routinely seems viable. If the usefulness of this type of surveillance system is confirmed, the resulting advantages to women's health in developing countries would be enormous if similar systems could be recommended and replicated as a strategy for safe motherhood.Although some limitations, the perspective of routinely using this information system for surveillance of near miss and implementing measures to avoid maternal death is promising.HIS: Hospital Information Systeml ICD: International Classification of Diseases; ICU: intensive care unit; MIS: Mortality Information System; MMR: Maternal Mortality Ratio; MNMR: Maternal near miss ratio; SINASC: Information System on Liveborn Infants.The authors declare that they have no competing interests.MHS and JGC participated in all steps of the study, including research planning, data collection, analysis and writing the manuscript. EEH and SJS participated in the project planning and review of the manuscript. All authors gave suggestions, read the manuscript carefully, fully agreed on its content and approved its final version.Click here for file


Web-based self-help interventions for problem drinking are coming of age. They have shown promising results in terms of cost-effectiveness, and they offer opportunities to reach out on a broad scale to problem drinkers. The question now is whether certain groups of problem drinkers benefit more from such Web-based interventions than others. We sought to identify baseline, client-related predictors of the effectiveness of Drinking Less, a 24/7, free-access, interactive, Web-based self-help intervention without therapist guidance for problem drinkers who want to reduce their alcohol consumption. The intervention is based on cognitive-behavioral and self-control principles. We conducted secondary analysis of data from a pragmatic randomized trial with follow-up at 6 and 12 months. Participants (N = 261) were adult problem drinkers in the Dutch general population with a weekly alcohol consumption above 210 g of ethanol for men or 140 g for women, or consumption of at least 60 g (men) or 40 g (women) one or more days a week over the past 3 months. Six baseline participant characteristics were designated as putative predictors of treatment response: (1) gender, (2) education, (3) Internet use competence (sociodemographics), (4) mean weekly alcohol consumption, (5) prior professional help for alcohol problems (level of problem drinking), and (6) participants’ expectancies of Web-based interventions for problem drinking. Intention-to-treat (ITT) analyses, using last-observation-carried-forward (LOCF) data, and regression imputation (RI) were performed to deal with loss to follow-up. Statistical tests for interaction terms were conducted and linear regression analysis was performed to investigate whether the participants’ characteristics as measured at baseline predicted positive treatment responses at 6- and 12-month follow-ups.P = .05, 2R = .11). At 12 months, females displayed modest predictive power in both imputation models . Those with higher levels of education exhibited modest predictive power in the LOCF model only . At 6 months, prior help for alcohol problems predicted a small, marginally significant positive treatment outcome in the RI model only : 47285230; http://www.controlled-trials.com/isrctn47285230 (Archived by WebCite at http://www.webcitation.org/5cSR2sMkp). Problematic alcohol use is not only a pervasive individual problem; it also imposes serious health and social burdens on the general population ,2,3. ThiIt is well known that treatment response is not influenced by treatment alone . A numbed = 0.40, 95% CI 5.86 - 18.10; P < .001). At 12 months, the difference between the groups had faded , mainly due to a further decrease in alcohol consumption in the control group. Results of this pragmatic randomized trial have been reported elsewhere [We therefore investigate here whether specific baseline characteristics can be identified as predictors of a positive treatment outcome for problem drinkers in the Dutch population who completed a Web-based self-help intervention called Drinking Less. On the basis of predictors already reported in the literature, we hypothesized that six putative baseline characteristics—(1) female gender, (2) higher education, (3) Internet competence, (4) a moderate level of problem drinking, (5) prior professional help for problem drinking, and (6) high expectancy for positive results from a Web-based intervention—would interact with Drinking Less to predict a more favorable treatment outcome at follow-up. We conducted a secondary analysis of our Drinking Less trial data  to examilsewhere .To the best of our knowledge, this is the first article that uses randomized trial data to assess predictors of short- and longer-term outcomes in Web-based self-help for problem drinkers in the general population.Data were retrieved from a pragmatic randomized trial with two parallel groups using block randomization stratified for gender, with follow-up at 6- and 12 months . In brieWe kept our exclusion criteria to a minimum to facilitate a low-threshold inclusion strategy consistent with the nature of self-help interventions without therapeutic guidance. We therefore did not conduct diagnostic interviews. After screening and baseline assessment, participants were randomly assigned to the experimental condition (the Drinking Less intervention) or to the control condition  . We sele                    Participants in the experimental condition received access to the Drinking Less intervention . Drinkin                    Our choice of baseline participant characteristics as putative predictors was based on theoretical assumptions and results from previous prediction studies -22. We sThe outcome measure was defined as the individual differences between baseline (T0) mean weekly alcohol consumption and the mean level of consumption at posttreatment  and at follow-up  in the total group. Alcohol consumption was assessed with the Dutch version of Weekly Recall (WR) ,33. It rt-tests, chi-square tests, and logistic regression to assess whether the randomization had resulted in two comparable groups at baseline and whether any differential loss to follow-up had occurred. We then performed intention-to-treat (ITT) analysis, using last-observation-carried-forward (LOCF) data and regression imputation (RI) to deal with loss to follow-up. Overall loss to follow-up was high . Values on the WR scale were transformed into a variable distinguishing moderate problem drinking  from severe problem drinking (> 35 or > 50 units women/men). Categorical variables with more than two categories were recoded into two meaningful categories: (1) education: high/low ; (2) Internet competence: experienced/beginner; (3) prior professional help for alcohol problems: yes/no; and (4) expectancies of Web-based intervention: high/low. We then applied regression analyses to ascertain whether these particular groups benefited more from the intervention than others. We assessed the interactions between the above-baseline attributes and the Drinking Less intervention modality, and then the effects of those interactions on treatment outcome. In this model, the standardized individual change scores (pre- to post-intervention effect sizes) served as the dependent or outcome variable. The interaction terms of each participant characteristic with the intervention dummy  served as independent predictor variables, along with their constituent main effects.P < .05. Independent-samples t-tests were used to analyze differences between the conditions in terms of problem drinking outcome at T1 and T2. This technique permitted us to test for the differential effects of the predictors in interaction with the Drinking Less treatment. It also enhanced the power to detect effects. If neither of these interaction terms proved significant, then the effect of the predictor was deemed not to be modified by Drinking Less. That is, the effect of Drinking Less on drinking outcome could not be explained by the predictor’s modifying effect on the relationship between treatment and outcome.We next calculated the product of the intervention dummy and each of the dummy variables describing the participants’ characteristics ,37. The We subsequently repeated this procedure in completers-only analyses on those participants who completed the follow-up questionnaire at 6 months (n = 151) or at 12 months (n = 163) to verify whether the results of the two ITT analyses would be sustained. Finally, we used descriptive statistics to illustrate the changes in alcohol consumption over time in terms of the identified predictors. The sample size provided 24 participants per variable at 6 months and 26 per variable at 12 months . All anaP < .10 to ensure against marginal differences that could affect results). This indicated that the randomization was successful. At baseline, all 261 participants (100%) were exceeding the mean number of weekly alcohol units set by the Dutch guideline for sensible drinking for healthy adults. Mean weekly alcohol intake was 43.6 standard units (SD = 21.6). More than half the sample belonged to the category of moderate, as opposed to severe, problem drinkers . The female-to-male ratio was almost 1:1. Two-thirds of participants had high educational backgrounds . Most participants considered themselves experienced Internet users . Almost half had positive expectations of the intervention . The large majority of participants  were in the contemplation stage of change, meaning that they wanted to reduce their alcohol consumption in the near future [The demographic and clinical characteristics of participants at baseline are shown in r future ,40. MostP > .10; 2                    1 = 1.71, P = .19). At 12 months, loss to follow-up was 37% (n = 98) and was greater in the experimental condition  than in the control condition . Non-responders at 12 months had a higher baseline mean weekly alcohol intake as measured by WR  than non-responders .Participants who did not return the questionnaire 6 months after baseline did not differ from posttreatment responders in terms of the characteristics assessed at baseline  and the completers-only model. We therefore present here only the intention-to-treat models. Results of the completers-only analysis are available from the first author.P = .05, 2R = .11). At 12 months, female gender predicted successful alcohol reduction in both analysis models , while the LOCF model showed a less strongly significant impact and a lesser amount of explained variance . High education level was identified as an additional predictor of successful outcome at 12 months. The LOCF analysis  showed a significant but modest effect and accounted for a small fraction of the variance in treatment outcome, but the effects in the RI model were not significant.Analyses of predictor-by-treatment interaction effects in terms of a successful reduction of mean weekly alcohol use found no significant effects for the putative predictors at 6 months , with ths models . RI indiWe compared the mean weekly alcohol consumption at 6 and 12 months for the two conditions as shown by the intention-to-treat and completers-only analyses. The last-observation-carried-forward (LOCF) model appeared to be the most conservative estimation method for the total group, as it returned the highest alcohol intake in both conditions—thus suggesting less improvement. We therefore chose these more cautious LOCF results to report outcomes for the two main predictors identified in our analysis. Detailed information about the other two models can be obtained from the first author.                                        At 6 months, the more highly educated Drinking Less  participants had achieved the greatest reduction in both absolute and relative terms  as compared to other categories . Althoug                    The aim of this study was to determine whether some groups would benefit more than other groups from Drinking Less, a Web-based self-help intervention for problem drinkers, when assessed at 6 and 12 months. We investigated six characteristics of the participants at baseline as putative predictors of treatment response: (1) female gender, (2) high level of education, (3) high Internet experience, (4) moderate as opposed to severe level of problem drinking, (5) prior professional help for alcohol-related problems, and (6) high expectancies for Web-based intervention.At the 6-month follow-up, we could not convincingly establish predictive value for any of these putative predictors, with the possible exception of prior help for alcohol problems, which was only marginally significant under the regression imputation model. Some other studies have likewise identified prior professional help as a predictor of positive client-by-treatment interaction leading to successful outcomes . An explAt 12 months, we found a modest prognostic value for female gender and for higher education; both variables were associated with better treatment response to the Drinking Less self-help intervention. Women who completed the intervention were found to have reduced their alcohol consumption to a significantly greater extent than men or than control group participants. Comparable results for female gender as a predictor of a successful brief intervention outcome in general population samples were reported by Sanchez-Craig and colleagues  and, to Higher levels of education also had modest predictive power and explained a small amount of variance at 12 months in combination with Drinking Less. This finding is consistent with results from other studies that identified high education as interacting with treatment interventions to produce favorable outcomes ,45. LikeThe other characteristics investigated were not found to act as predictors in our study. A moderate baseline level of problem drinking  did not predict better outcomes than a severe level. This contrasts with the many studies that assume brief interventions to be better suited to moderate problem drinkers . One expWe did not find any predictive value for the two remaining putative predictors, Internet experience and positive expectancies of treatment efficacy, in contrast to some other studies that did ,48. ExplThis study has several limitations that are important to acknowledge. We conducted secondary analysis of data from our pragmatic randomized trial .The overSecondly, we conducted a prespecified subgroup analysis and hence cannot rule out false-positive or false-negative predictors resulting from multiple testing ,54. GiveWe were also limited by the data in the number of predictors we could investigate. That prevented us from studying self-efficacy, a potentially important predictor . Nor couOur study has a number of strengths as well. The study on which the analysis is based was one of the first pragmatic randomized trials on the effectiveness of Web-based self-help interventions without therapeutic guidance for problem drinkers in the general population. The data also enabled us to examine short- and longer-term relationships. Because we had anticipated a high overall loss to follow-up when we first selected the trial sample, we included enough participants to ensure the statistical power to detect differences between the experimental and control conditions and between subgroups .Female gender and a high level of education were found to have interacted with the Drinking Less self-help intervention to predict a somewhat better treatment response one year after the start of the intervention. This suggests that Web-based self-help without therapeutic guidance may hold a special attraction for problem drinkers with greater fears of stigmatization, including women or more highly educated people—population segments that might otherwise be difficult to reach with face-to-face brief interventions . The nonAt the same time, the effects of the predictors identified here offer only a very partial explanation for how client characteristics interact with treatment to affect outcome. Other baseline attributes such as self-efficacy may also play a role . In addiOur findings could enhance public health strategies that use stepped-care approaches to curb problem drinking in the general population. Since none of the groups we identified stood out conspicuously against others as deriving benefit from Drinking Less, we would argue that Web-based self-help is well suited to a broad, heterogeneous group of problem drinkers. It may therefore serve well as an initial intervention in a stepped-care model, suitable for matching to a large and varied group of problem drinkers in the general population and not just at more individual levels ,59. The Our results add to the knowledge already gained from prediction studies in that we tested the role played by individual baseline attributes in the effectiveness of Web-based self-help for problem drinkers in the general population. The scope of future prediction research now needs to be extended to include the contributions of within-treatment progress variables, such as dose-response relationships and the time required to initiate positive behavioral change, and of posttreatment variables like social support. Replication of our study is needed in view of the novelty of Web-based interventions for problem drinkers and the related prediction research.


In this work we used 31P NMR andfluorescence spectroscopy to determine the resting [Mg2+]i in bovine chromaffin cells, a neuron-like cellularmodel, as well as confocal laser scanning microscopy to study the free Mg2+ spatial distribution in these cells.31P NMR spectroscopy did not prove to be effective for the determination of [Mg2+]i in this particular case due to some special morphological and physiological properties of this cell type. A basal [Mg2+]i value of0.551 ± 0.008 mM was found for these cells using fluorescence spectroscopy and the Mg2+-sensitive probefuraptra; this value falls in the concentration range reported in the literature for neurons from differentsources. This technique proved to be an accurate and sensitive tool to determine the [Mg2+]i.Magnesium is an essential element for all living systems. The quantification of free intracellular Mg        2+ seems to be essentially localized in the nucleus and around it, as shown byconfocal microscopy with the Mg2+-sensitive probe Magnesium Green. It was not possible to derive anyconclusion about free Mg2+ localization inside the chromaffin granules and/or in the cytoplasm due to thelack of sufficient spatial resolution and to probe compartmentalization.lntraceilular free Mg


Objective: The role for acellular dermal matrix in implant-based breast reconstruction—providing coverage of the inferolateral border of the underlying prosthesis and allowing control over the inframammary fold—has become increasingly popular. Although AlloDerm  is free of cellular components responsible for the antigenic response, its processing does not guarantee sterility. In this study, we examine the infectious complications in tissue expander/implant-based reconstruction with AlloDerm. Methods: A retrospective cohort analysis was completed on 321 implant-based breast reconstructions over a 10-year period (1998–2008) at an academic institution. Of these cases, 75 reconstructions used AlloDerm and 246 reconstructions did not. The incidence of infections that required readmission for intravenous (IV) antibiotics and explantation was determined. Prosthetic explants due to hematoma or patient dissatisfaction were excluded from analysis. Results: There were no differences in rates of readmission for IV antibiotics . The rate of explantation due to infected fluid collections and extrusion was higher in the AlloDerm group  than that in the control group . This result was statistically significant (P = .013). Conclusion: In this study, the rates of IV antibiotic administration for the treatment of cellulitis in implant-based breast reconstructions did not differ because of the presence of AlloDerm; however, the rate of explantation was statistically higher in reconstructions using AlloDerm. This technique has great potential in breast reconstruction, especially for single-staged implant-based reconstruction, but careful counseling of patients with regard to the higher risk of explantation is necessary. The remaining matrix components include collagen, fibronectin, elastin, hyaluronan, and proteoglycans, which can be incorporated by the surrounding soft tissue.7All patients undergoing expander/implant-based primary breast reconstruction over a 10-year period from 1998 to 2008 at a single academic institution were examined. A total of 321 primary expander/implant-based reconstructions were identified, including 75 AlloDerm-based reconstructions and 246 reconstructions without AlloDerm. Patients with primary autologous reconstruction and subsequent expander/implant reconstruction were excluded.Cellulitis was defined as erythema in conjunction with a fever or an elevated white blood cell count. Prosthetic explantations due to patient dissatisfaction were excluded from analysis. All surgeons in this study used 1 drain per breast at the time of reconstruction. There was no standard antibiotic or irrigation protocol.A retrospective chart review was performed from online medical records to collect information regarding patient demographics, procedure details, and surgical outcomes. Information concerning patient demographics, procedure details, and surgical outcomes were obtained from online medical records and inpatient hospital records. Specific data included patient comorbidities , radiation treatment, and immediate or delayed breast reconstruction. The 2 primary outcomes of the study are the incidence of cellulitis requiring readmission for intravenous (IV) antibiotics and expander/implant removal due to infected fluid collection or extrusion. t test. The Fisher exact test was used to compare the primary outcomes . Logistic regression analysis was used to compare the relationship between radiation therapy (radiation or no radiation) and reconstruction timing (immediate or delayed) with each of the primary outcomes. Differences in late complication outcomes were analyzed by using the chi-square test and the Fisher exact test.We assessed differences in patient characteristics by using the chi-square test, the Fisher exact test, and the 2-sample P < .05.This study was approved by the Institutional Review Board at Beth Israel Deaconess Medical Center. Statistical analysis was performed using SPSS  and SAS  statistical software package. Statistical significance was set at There was no difference in the patient characteristics between the AlloDerm and traditional implant-based reconstructions Table . The meaP = .291). In contrast, the explantation rate was significantly higher in the reconstructions using AlloDerm . In addition, neither radiation therapy (Table Analysis of the readmission rates for IV antibiotics to treat cellulitis after breast reconstruction with an implant or expander revealed that there was no difference due to the presence of AlloDerm Table . The ratpy Table  affectedThe use of AlloDerm for immediate implant-based and expander/implant reconstructions has become popular in the past 4 years. The reported benefits of this technique include improved cosmetic appearance, decreased chest wall morbidity, and decreased time of reconstruction. It was first described by Brueing and WarrenThe traditional dictum in the setting of an infected prosthetic is removal followed by delayed reconstruction because this provides the safest and most conservative course. Salvage of an infected implant is associated with a high rate of late capsular contracture. Courtiss et al-7-P = .013; Table In our study, the rate of inpatient readmission for IV antibiotics is 5.3% for AlloDerm-based reconstructions. This rate is similar to the readmission rates for traditional implant-based reconstructions at our institution, as well as to the previously published infection rates for the use of the AlloDerm sling.1The most likely explanation for this difference is a learning curve. Since AlloDerm is juxtaposed next to a prosthetic device, there is a lower threshold for explantation to eliminate the infection, as the AlloDerm is not guaranteed to be sterile. A recent case report examined possible salvage of an infected AlloDerm-based implant reconstruction with a vacuum-assisted closure device; however, more patients and longer follow-up is necessary.Although we believe that AlloDerm can be a valuable tool as a method of providing a single-stage, implant-based breast reconstruction, patients should be counseled that there is currently a higher explant rate with AlloDerm sling method than that with the traditional methods. As we gain more experience, this may improve.


To further develop this compound we modified its structure to obtain more potent inhibitors of the PI3K/Akt pathway.Owing to its role in cancer, the phosphoinositide 3-kinase (PI3K)/Akt pathway is an attractive target for therapeutic intervention. We previously reported that the inhibition of Akt by inositol 1,3,4,5,6-pentakisphosphate  is active towards cancer types resistant to InsP5in vitro and in vivo. 2-O-Bn-InsP5 possesses higher pro-apoptotic activity than InsP5 in sensitive cells and enhances the effect of anti-cancer compounds. 2-O-Bn-InsP5 specifically inhibits 3-phosphoinositide-dependent protein kinase 1 (PDK1) in vitro (IC50 in the low nanomolar range) and the PDK1-dependent phosphorylation of Akt in cell lines and excised tumours. It is interesting to note that 2-O-Bn-InsP5 also inhibits the mammalian target of rapamycin (mTOR) in vitro.The derivative 2-5 and 2-O-Bn-InsP5 may represent lead compounds to develop novel inhibitors of the PI3K/Akt pathway  and novel potential anti-cancer drugs.InsP Phosphorylation of Thr308 is mediated by 3-phosphoinositide-dependent protein kinase 1 (PDK1), which itself possesses a PH domain able to bind PtdInsP3  isoforms catalyse the phosphorylation of the 3-hydroxyl group within the inositol ring of phosphoinositides generating lipid products, which in turn mediate the activation of several proteins . Upon PI3 either due to gain of function of PI3K activity  specifically blocks Akt activation and possesses pro-apoptotic  exhibits more efficient and potent activity than InsP5 not only in inhibiting Akt phosphorylation but also in inducing apoptosis in different human cancer cell lines. It is interesting to note that 2-O-Bn-InsP5 promotes apoptosis in cell lines normally resistant to treatment with InsP5 and markedly inhibits the in vivo growth of InsP5-resistant xenografts. Kinase profiling analysis reveals that 2-O-Bn-InsP5 strongly inhibits PDK1 activity in vitro with an IC50 in the low nanomolar range. This is mirrored by the inhibition of Akt phosphorylation at its residue Thr308 in 2-O-Bn-InsP5-treated cells and in tumours from 2-O-Bn-InsP5-treated mice. Furthermore, the effect of 2-O-Bn-InsP5 is highly specific, as this compound only inhibits PDK1 and to a lesser extent mTOR in a panel of almost 60 kinases. These data represent the first attempt to exploit InsP5 as a potential lead compound for the development of potent small molecule inhibitors of the PI3K/Akt pathway.In order to explore early structure-activity relationships for InsPO-Bn-InsP5 was synthesised in a similar manner from 2-O-benzyl-myo-inositol. Each compound was purified to homogeneity by ion-exchange chromatography on Q-Sepharose Fast Flow resin  and used as the triethylammonium salt, which was fully characterized by 31P and 1H spectroscopy and accurately quantified by total phosphate assay. For the in vivo experiments, InsP5 and 2-O-Bn-InsP5 were each converted into the hexasodium salt by treatment with Dowex 50WX2-100 ion-exchange resin , followed by addition of sodium hydroxide  and lyophilisation. Sulphorhodamine (SRB), curcumin, paclitaxel and 4-hydroxy-tamoxifen were purchased from Sigma-Aldrich; anti-phospho Ser473 Akt, anti-phospho Thr308 Akt and anti-Akt from  or Santa Cruz Biotechnology .Inositol 1,3,4,5,6-pentakisphosphate was synthesised as previously reported . After 72 h, the number of surviving cells was assessed by manual cell counting or by using the cell counter CDA-500 . Alternatively, after 48 h, the number of apoptotic cells was assessed by acridine orange/ethidium bromide assay as described  were obtained from Harlan  and maintained under specific pathogen-free conditions with food and water provided −1 InsP5 or 2-O-Bn-InsP5/mouse administered intraperitoneally (i.p.). Each group consisted of 2–3 mice. Body weight, deaths and any other sign of toxicity and changes in behaviour  were recorded.Male nude CD-1 mice were treated with a single dose of 750 mg kg7 cells ml−1. A suspension of 5 × 106 PC3 cells was injected subcutaneously (s.c.) into the left flank of the recipient mice. When tumours reached a size of ∼70 mm3 (approximately 15 days after tumour cell implant), mice were divided into seven groups (n=7). InsP5 and 2-O-Bn-InsP5 were administered by daily i.p. injections at different doses of 12.5–25–50 mg kg−1 day-1 for 14 consecutive days. Control mice were treated with water in an equal volume. The diameters of s.c. growing tumours were measured with a caliper twice a week and the experiment was ended at day 28 after the implantation.Exponentially growing PC3 cells were harvested, washed twice and resuspended in PBS at a concentration of 2.5 × 102)/2. Differences in s.c tumour growth between the treatment groups were evaluated with a one-way ANOVA followed by Fisher's test using the StatView statistical package . The percentage of tumour growth was calculated as T/C%= × 100, where RTV was the mean relative tumour volume calculated as RTV=Vt/V0. Vt was the tumour volume on the day of measurement and V0 was the tumour volume at the beginning of the treatment. The percentage of tumour weight inhibition (TWI%) was calculated using the formula: TWI%=100–T/C%. The log cell kill (LCK) was calculated using the formula: LCK=T−C/3.32 × Td, where T−C is the tumour growth delay calculated as the difference in median time (in days) required for the tumours in the treatment (T) and control group (C) to reach a predetermined size . Td is the tumour volume doubling time in days, determined in the exponential growth phase of the control group from a best-fit straight line. Median doubling time was 3 days in control animals.The volume of s.c. growing tumours was calculated by the formula: Tumour weight (mg)=(length × width5 and 2-O-Bn-InsP5 (50 mg kg−1) or vehicle. Animals were killed 24 h after treatment and tumour samples were collected and snap frozen. Frozen specimens of tumour tissue were homogenised with a Polytron homogeniser in a lysis buffer (ratio 1 : 1 w/v) containing 50 mM Tris-HCl (pH 7.4), 5 mM EDTA, 0.1% Nonidet NP-40, 250 mM NaCl, 50 mM NaF and proteases and phosphatase inhibitors. After centrifugation at 13 000 r.p.m. for 10 min at 4°C, 80 μg of protein was separated on SDS–PAGE and transferred to a polyvinylidene difluoride membrane . Membranes were probed with the indicated antibodies.Mice with s.c. growing tumours were treated with a single dose of InsPμM of the tested compounds and ATP concentration as indicated in the corresponding tables. In the case of InsP5 a screen using 10 μM of the compound was also carried out, as indicated in the corresponding table.Effect of the indicated compounds on the activity of various kinases was assessed by SelectScreen Kinase Profiling Service . Assays were performed using 1 5 is a novel inhibitor of the PI3K/Akt pathway, which possesses pro-apoptotic, anti-angiogenic and anti-tumour activity P4 or InsP5. Different strategies were used to modify the parent molecules and several compounds were synthesised and tested. For InsP4-related compounds, modifications were made at C-6 because X-ray structures of the Akt P4 is not directly involved in binding. Furthermore, the X-ray structure of Akt PH domain showed that a tyrosine residue near the 6-OH of bound InsP4 might interact with an aromatic group. In the case of InsP5 analogs, modifications were on either the 2-O-atom or the 5-phosphate, thus maintaining the symmetry of the parent molecule. The derivatives were first tested for their ability to inhibit Akt activation in cell lines characterised by constitutive activation of the PI3K/Akt pathway and with a reported sensitivity to InsP5, namely ovarian cancer cells SKOV-3 and breast cancer cells SKBR3  showed the highest efficiency in inhibiting Akt activation in all cell lines tested (data on the other derivatives will be published elsewhere). More specifically, we found that 2-O-Bn-InsP5 inhibited Akt phosphorylation at its residue Ser473 more efficiently than InsP5 in SKOV-3, being already active after 8 h of treatment and at a concentration of 20 μM  of InsP5 or 2-O-Bn-InsP5 for 14 consecutive days (from day 15 to day 28). Tumour growth was followed for further 12 days after the end of the treatment (upto day 40). Data revealed that 2-O-Bn-InsP5 at doses of 12.5 and 25 mg kg−1 clearly decreased the growth of tumours compared with untreated mice, although the differences were statistically significant only on the last day of measurement  of almost 9 days between this group and the untreated (control) group. In agreement with our in vitro data, we observed that InsP5 had no effect on concentrations up to 50 mg kg−1  did not cause any major toxic effect . Among almost 60 protein kinases screened, 2-O-Bn-InsP5 (1 μM) showed a very high inhibitory activity towards PDK1 (79% inhibition) and a lower activity towards mTOR (O-Bn-InsP5 did not inhibit (percentage of inhibition <40%) any of all the other tested kinases, including AGC kinases, such as GSK3, RSK, S6K and members of the PKC family, AMPK and several members of the MAPK family  with only InsP4 also showing some effect (56% inhibition). None of the other polyphosphates had any significant effect  10-point titration revealed that the IC50 of InsP5 towards PDK1 was 613 nM whereas the corresponding IC50 of 2-O-Bn-InsP5 was a striking 26.5 nM  for 72 h reduced the number of surviving cells, whereas 2-O-Bn-InsP5 had little effect . A combination of 2-O-Bn-InsP5 and curcumin, a component of turmeric (Curcuma longa), strongly reduced the number of surviving PC3 cells, resulting in a more than additive effect . It is noteworthy that PDK1 and mTOR were the only enzymes to be inhibited by 2-O-Bn-InsP5 in a screen of almost 60 different kinases, indicating that 2-O-Bn-InsP5 may represent an interesting lead compound to design novel and potent dual PDK1 and mTOR inhibitors.The O-benzyl-myo-inositol 1,3,4,5,6-pentakisphosphate was selected in a screen of several different compounds that we synthesised and first tested for their ability to inhibit Akt phosphorylation in cells sensitive to InsP5. In this original screen, 2-O-Bn-InsP5 was not only more efficient than the parent molecule in inhibiting Akt phosphorylation and inducing apoptosis in InsP5-sensitive cell lines but it was also able to induce apoptosis in InsP5-resistant cell lines including pancreatic cancer cells. The pro-apoptotic activity of 2-O-Bn-InsP5 detected in pancreatic cancer cells represents an extremely important result taking into account the high resistance of this cancer to chemotherapeutic treatment and the urgent need for novel therapeutics in clinical treatment. Furthermore, 2-O-Bn-InsP5 was able to inhibit the in vivo growth of InsP5-resistant prostate cancer xenografts. It is noteworthy that, although 2-O-Bn-InsP5 acted in the micromolar range in in vitro studies, it was able to inhibit tumour growth in vivo at 12.5, 25 and 50 mg kg−1, doses commonly used to test the in vivo effect of potential anti-tumour compounds. In particular, 2-O-Bn-InsP5 induced a tumour weight inhibition of 52% in prostate cancer xenografts when dosed at 50 mg kg−1 once daily for 14 days.2-5 and 2-O-Bn-InsP5, and to explain the higher activity of 2-O-Bn-InsP5 compared with the parent molecule. Our previous and current data demonstrated that the in vitro and in vivo properties of InsP5 and 2-O-Bn-InsP5 were because of reduced Akt phosphorylation and activation , thus indicating that the detected Akt inhibition is due to blockade of the activity of its upstream regulatory kinase. This is consistent with the observed enhanced activity of 2-O-Bn-InsP5 compared with InsP5, likely due to its higher inhibitory activity towards PDK1. Furthermore, this difference could explain the strong effect of 2-O-Bn-InsP5 in InsP5-resistant cell lines such as the PTEN mutant cells MDA-MB-468 and PC3, and would be consistent with the proposed key role of PDK1 in tumourigenesis driven by Pten loss  may prove particularly useful in combinatorial therapies. In particular 2-O-Bn-InsP5 increases the effect of tamoxifen in breast cancer cells MCF7, consistent with the reported role of PDK1 inhibition in tamoxifen sensitisation . This raises the interesting possibility that the endogenous intracellular InsP5 may act as an endogenous PDK1 inhibitor and regulator of the PI3K/Akt pathway. This hypothesis is currently being investigated in our laboratory.It must be noted that, like InsPin vitro and in vivo properties of 2-O-Bn-InsP5, a derivative of InsP5, which possesses similar solubility and lack of toxicity in vivo but enhanced pro-apoptotic and anti-tumour activity compared with the parent molecule. In particular 2-O-Bn-InsP5 possesses specific inhibitory activity towards PDK1. Data also indicate that 2-O-Bn-InsP5 can inhibit mTOR, at least in vitro. It is interesting to note that InsP5 does not possess such an inhibitory activity towards mTOR, thus suggesting that comparison of the two molecules can give useful information towards developing specific dual PDK1/mTOR inhibitors. Taken together these data indicate that InsP5 and 2-O-Bn-InsP5 may represent promising models for further development of novel anti-cancer drugs.In conclusion, here we have described the


Alcohol is a leading risk factor for avoidable disease burden. Research suggests that a drinker's social network can play an integral role in addressing hazardous  or problem drinking. Often however, social networks do not have adequate mental health literacy . This is a concern as the response that a drinker receives from their social network can have a substantial impact on their willingness to seek help. This paper describes the development of mental health first aid guidelines that inform community members on how to help someone who may have, or may be developing, a drinking problem .A systematic review of the research and lay literature was conducted to develop a 285-item survey containing strategies on how to help someone who may have, or may be developing, a drinking problem. Two panels of experts (consumers/carers and clinicians) individually rated survey items, using a Delphi process. Surveys were completed online or via postal mail. Participants were 99 consumers, carers and clinicians with experience or expertise in problem drinking from Australia, Canada, Ireland, New Zealand, the United Kingdom, and the United States. Items that reached consensus on importance were retained and written into guidelines.The overall response rate across all three rounds was 68.7% , with 184 first aid strategies rated as essential or important by ≥80% of panel members. The endorsed guidelines provide guidance on how to: recognize problem drinking; approach someone if there is concern about their drinking; support the person to change their drinking; respond if they are unwilling to change their drinking; facilitate professional help seeking and respond if professional help is refused; and manage an alcohol-related medical emergency.The guidelines provide a consensus-based resource for community members seeking to help someone with a drinking problem. Improving community awareness and understanding of how to identify and support someone with a drinking problem may lead to earlier recognition of problem drinking and greater facilitation of professional help seeking. The global consumption of alcohol is growing at a rapid rate, making it the fifth leading risk factor for avoidable disease burden . The heaResearch suggests that community interventions can play an integral role in addressing problem drinking. For instance, there is growing evidence that the social networks of individuals with a drinking problem are an important source of support and assistance . Often hIn response to poor mental health literacy within the community, Kitchener and Jorm  developehttp://www.mhfa.com.au/Guidelines.shtml). Expert consensus (viz. the Delphi process) was used to identify suitable first aid strategies, as randomized controlled trials of component first aid strategies are not feasible. The Delphi process involves a group of experts making private/independent ratings on a series of items. The experts receive a statistical summary showing how the entire group rated the items and are asked to reconsider their original ratings  in light of this feedback - the experts can either maintain or change their original items  questions are suitable advice for someone who is not dependent on alcohol". This concern was addressed by a sequence of items in the second round of the survey, encouraging the first aider to only provide information about low-risk drinking to the person if they wanted it. For example, The first aider should ask the person if they would like some tips on low-risk drinking. In addition, all low-risk drinking items from Round 1 that required re-rating were submitted to the panel in two forms in Round 2. Items were presented firstly in their original form  and secondly prefaced with If the person wants some advice on low-risk drinking, . Thus, rather than presenting the low-risk drinking tips as information that should be given to all drinkers, it was instead presented as information available to the first aider who could use it as deemed appropriate. This approach resulted in many low-risk drinking strategies being endorsed in the second and third rounds.A strength of the study was the inclusion of comment boxes which allowed panel members to give qualitative feedback about items within the survey. Panel members' explanations about why they rejected an item in Round 1 gave the authors valuable insight, often resulting in the resubmission of an item in Round 2 with different phrasing or emphasis to ensure an important concept was not rejected because of the way it was written. In the section about encouraging low-risk drinking strategies, participants raised concerns (the only time in the survey) about distinguishing between appropriate help for someone who is a high-risk drinker rather than someone who has alcohol abuse/dependence. In particular, there was concern that low-risk drinking strategies are not suitable for someone who is alcohol dependent. For example, a carer wrote, "The guidelines were based on consensus between international panels of clinical experts and consumers/carers. However, the small size of the panels and the difficulty recruiting carers must be acknowledged as limitations of the study. Despite approaching hundreds of organizations across six countries, we were unable to recruit enough carers to have a separate panel of carers. We had set a minimum panel size as 20, consistent with previous Delphi studies ,12. One Another limitation of the current study is that the guidelines have been developed specifically for Western, English-speaking countries. They therefore may not be applicable to non-Western cultures or to cultural minorities within English-speaking countries. However, there is scope to use the Delphi process to adapt the guidelines to specific cultures ,20. Thishttp://www.mhfa.com.au get useful information that guides their first aid actions. The guidelines are also being used to develop an improved second edition MHFA training course. Previous trials have shown the effectiveness of MHFA training in improving knowledge, reducing stigmatizing attitudes and increasing helping behaviour [Finally, although the guidelines are based on consensus of clinical experts, consumers and carers, the effectiveness of the endorsed first aid strategies remains to be tested. The guidelines document needs to be evaluated for its usefulness as a stand-alone source of information, as well as its utility in guiding the content of training programs. To evaluate the guidelines as a stand-alone document, we are currently doing research on whether people who download it from a website ehaviour -26, and ehaviour . HoweverIn conclusion, these guidelines provide first aid strategies that have been agreed upon by an international panel of clinicians, carers and consumers with expertise and/or experience in problem drinking. The guidelines will provide an important resource for community members seeking to help someone with a drinking problem, hopefully leading to earlier recognition and greater facilitation of professional help seeking. Future research should assess the effectiveness of the first aid strategies endorsed within these guidelines to ensure that they increase helping behaviour and reduce stigma.The authors declare that they have no competing interests.AJ and DL designed the study and wrote the protocol with input from BK, CK, LH and AK. AK completed the literature review, initial survey construction, recruitment of participants, data collection and analysis, and prepared drafts of the guidelines. A working group, consisting of AJ, BK, DL, AK, LH, CK, AM and LH, gathered regularly to give feedback and make improvements on each draft of the Rounds 1, 2 and 3 surveys and the final guidelines. AK wrote the first draft of the manuscript with input from DL and AJ. All authors contributed to and have approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-244X/9/79/prepubItems that received ≥80% consensus across both the consumer/carer and clinician panels.Click here for fileHelping someone with problem drinking: Mental Health First Aid guidelines. This file may be distributed freely, with the authorship and copyright details intact. Please do not alter the text or remove the authorship and copyright details.Click here for file


P <0·001) higher than in a healthy control group, but after local therapy the concentration was significantly lower than before treatment (P <0·01). The concentration of conjugated 3OHA was nearly constant in the three groups. It was concluded that other factors than a genetic determined abnormality might be operating in bladder cancer patients which could lead to an abnormal concentration of 3OHA in their urine.The basal concentration of the tryptophan metabolite 3-hydroxyanthranilic acid (3OHA), which has carcinogenic properties, was measured with an enzymatic method of determination which allowed separate measurement of free and conjugated 3OHA. The concentration of free 3OHA in untreated bladder cancer patients was significantly (


By webcasting the hundreds of seminars presented in the University of California system each week, UC educators hope to enhance the exchange of scientific information for their campuses and create the foundation for an international research seminar network. The infectious enthusiasm of scholars speaking about their research is often perfectly complemented by the never-ending quest of academic audiences for new knowledge, making seminars one of the most forceful and efficient mechanisms for transmitting scholarly information. Indeed, seminar attendance is an integral part of the experience for University of California (UC) researchers, with an estimated 300 to 500 seminars during a typical week of the academic year across 900 departments or programs in the UC system. This translates to well over 10,000 seminars annually that are presented in diverse formats and various frequencies—weekly department, graduate group and center seminars, monthly or quarterly talks in distinguished scholar lecture series, and annual university lectures by eminent faculty.Although the importance of sponsoring and attending research seminars is universally acknowledged by UC scholars and administrators, time and travel constraints limit the potential for maximizing transmission and exchange of the massive amount of information contained in these seminars. The schedules of researchers (particularly faculty) are often packed so tightly that they cannot accommodate the additional time needed to walk to many seminars on their own campus, let alone travel to a neighboring campus. Consequently, the number of UC researchers who attend seminars on UC campuses other than their own is negligible.The UC Seminar Network was conceived as a way to address these time constraints and open up numerous new possibilities for information exchange by delivering scientific presentations to a researcher's office computer using webinar technology that links seminars across the 10-campus UC system. This network would increase intra-, inter-, and off-campus seminar access, encourage speaker sharing, reduce travel, augment outreach, and provide electronic feeds for on-demand streaming and archiving.http://webcast.berkeley.edu/) is a lecture webcasting system developed by the UC Berkeley Multimedia Research Center in conjunction with UCB's Education Technology Services (ETS) to stage and videotape on-site events and publish them online for on-demand viewing. The UC Regents retain the copyright to all media recordings. (2) University of California Television (UCTV) (http://www.uctv.tv/ondemand/) is a non-commercial channel featuring programming from throughout the UC system. Programs, transmitted by television or through the Web, include documentaries, faculty lectures, research symposia, and artistic performances, as well as postings related to K–12 education and a Med Ed Hour that offers up-to-date research on health and medicine. (3) Technology, Entertainment, Design (TED)—these 4-day conferences (http://tinyurl.com/kpmvbo), run by the not-for-profit Sapling Foundation in New York City, have a strict time limit of 18 minutes, incorporate no audience interactions, include few or no PowerPoint slides, and emphasize speaker engagement at a scientifically untutored listener level. Presentations are delivered, recorded and edited using state-of-art technology, with extraordinarily high quality products posted for on-demand viewing. (4) National Institute of Health (NIH) VideoCasting—the Center for Information Technology (CIT) makes special events, seminars, and lectures available on the NIH network and their VideoCast website (http://videocast.nih.gov/PastEvents.asp). The talks by invited scientists  feature original research in, for example, biology, medicine, and bioethics.To provide both context and perspective for creation of the UC Seminar Network, we briefly describe four seminar webcasting enterprises. (1) webcast.berkeley , of basic checklists to reduce the risk of mistakes, and use of background drapes and/or podium logos to identify the department/university as well as to provide a clean and professional looking set. An important operational principle applied to all seminars was that any problems that were encountered with the equipment were not allowed to delay seminar start-times.It's likely that a UC seminar network would improve the quality of many seminar, as speakers often take talks more seriously when they know their presentation will be recorded and transmitted widely. Additionally, invited speakers and job applicants could be prescreened from their video-streamed or on-demand seminars. On-demand videos could also be used in training modules for undergraduate, graduate, and professional students. Finally, a seminar network would heighten UC scientist's awareness of the remarkable diversity of off-campus UC research sites with talks originating from locations ranging from the Scripps Institute of Oceanography in La Jolla and the Los Alamos National Laboratory in New Mexico to the Burns Piñon Ridge Reserve in the Mohave Desert and the Gump South Pacific Research Station in French Polynesia.Inasmuch as most UC research is funded by taxpayers, it can be argued that the public should have direct if not immediate access to the results UC Seminar Network would become part of a University Seminar Network which, in turn, could become part of a global Research Seminar Network. Because many thousands of weekly seminars across all time zones and areas of science would be listed on an international website, the postings would need to be sorted by topic or key word and/or be listed according to interest group , time zone/region, and language. As researchers become more comfortable with the webinar concept, seminar series can begin being organized in new configurations involving institutions in different time zones and on different continents  with a mid-morning seminar presented in Berkeley being viewed as an early evening seminar in Tel Aviv.As other university systems and institutional clusters adopt a similar idea for making their seminars available via webinar technology, the Research seminars are concerned with transmitting new knowledge rather than, for example, disseminating marketing data as in business seminars or delivering information on nutrition in public health seminars. Given the central role of research at UC, expanding the scale of research seminar webcasting and developing a more comprehensive infrastructure for their access, cataloging, and storage has the potential to increase both the number and specificity (relative to interests and expertise) of seminars available to UC researchers and thus enhance the flow and exchange of new knowledge within the system. Of course, the concept of using webinar technology is not new to the UC system since, as noted previously, the not-for-profit TV channel UCTV as well as the webcast.berkeley program, have been recording and transmitting high-end seminars for a number of years. By providing live video streams and on-demand records of all seminar types, the UC Seminar Network would complement both of these webcasting enterprises, with each representing a component of a larger communications enterprise.Editor's Picks, Most Viewed, and Highlights of Week. Indeed, the recorded seminars can become part of the liquid fabric of all information contained within a universal library infrastructure, fostering a new culture of interaction and participation.As part of one of the world's largest and most prestigious library systems, the California Digital Library (CDL) would clearly play a central role in developing the seminar network by providing expertise on how best to catalog, store, preserve, and retrieve recorded seminars. It is conceivable that video records of scientific seminars may become a bibliographic (and thus both searchable and citeable) concept much like that for many news organizations, complete with on-demand videos showcased as As the research arm of the state, the University of California is currently exploring the concept described here concerned with linking seminars systemwide as a mechanism to both enhance and accelerate research. Although current budgetary issues as well as technological constraints may limit development in the short term, continued field testing of seminar webcasting can still vet the concept, quantify the level of interest, and evaluate the technology. In light of trends in science, technology, the Internet in general, and the on-going seminar webcasting of a number of programs including NIH, TED, UCTV, and webcast.berkeley, it is likely that the seminar network system described here or a close variation thereof will begin to emerge throughout the research communities and eventually merge into national and then global networks of research seminar interconnectivity.Webcasting is a generic concept referring to the transmission of linear audio or video content over the Internet and can occur in a number of forms web conference consisting of many-to-many connections, a webinar consisting of one-to-many connections , and podcasts  referring to episodic releases of webcast lectures or webinars. A webcast is created through the use of special web conferencing software such as the multimedia program Adobe Acrobat Connect Pro, which electronically streams encoded video/audio data from a lecture to a server and then to an online audience. The different types of webcasts are distributed from the web server as either a file or a stream, the first providing the user the ability to play the webcasts multiple times offline  and the latter allowing the user to skip portions of the file without completely downloading it. For both on-demand viewing and archiving, the digital data containing the audio and video information are stored electronically either in a local digital storage device or through a service such as iTunes U .Although there are a number of important exceptions , webcasting technology is currently used in academia much less than in other areas such as business, law, and medicine. Indeed, webinars are relatively rare for talks given in distinguished seminar series and are almost non-existent for talks presented in more routine seminar series.Seminar webcasting will involve copyright of the seminar content and copyright of the actual seminar recording. Copyright ownership is governed by several UC copyright policies and depends primarily upon the relationship of the presenter to UC . For purposes of this paper, the copyright to the content of most academic seminars will belong to the speaker, while the copyright to that particular recording of the talk belongs to the UC Regents Streaming live presents few copyright issues so long as the viewing sites are classroom-like, limited to UC viewers, and the speakers sign a consent form allowing the broadcast (see S1). Later broadcast, however, requires more steps. For members of several UC campuses,  publishing their own presentation can be done relatively easily through iTunes U through a three-step process. Campuses which are not currently participating in iTunes U may have similar tools available. The presenter is responsible for two types of permissions:Permission 1. Individuals who participate in the presentation  and could be recognized must voluntarily consent to the recording using a form which is available through the iTunes U process  that addresses all phases of copyright.Other kinds of direct-to-web exposure in seminars have the potential to create thorny IP problems that are currently unresolved. For example, science-bloggers can—and often do—photograph and immediately post slides on their blog site while attending meetings or seminars. This can create problems for applied researchers who must file patent applications within a year of any information becoming public Successful development and implementation of the UC Seminar Network concept, much like distance learning The following is a general description of how the proposed UC Seminar Network would work.Announcements. Key information  entered to campus website by sponsoring department or unit along with a URL address for accessing seminar via video streaming. This information would be distributed to a central seminar listing website for all UCs using the Shibboleth Authentication System.Speakers. Seminar speakers will be given an “opt in” choice for having their seminar webcast by requesting that they sign the “consent to record” form. Some committees responsible for distinguished lecturer series offering generous honoraria to speakers might consider mandating webcasting to all invitees.Technology. Minimal requirements for weekly seminar series would involve camera, laptop, microphone, and appropriate video streaming hardware/software. Graduate students  would set up equipment and log in to the webcasting site. More sophisticated equipment and IT personnel would be used for seminars involving distinguished speakers.Mechanics. Speakers would be required to use the microphone and asked to restrict their movements to the podium area. The tripod-mounted camera operated by a videographer would be trained on the speaker at the podium. The host would be responsible at the start for introducing the speaker and at the end for directing questions from the in-person audience as well as for reading selected emailed queries. Straightforward protocols would be distributed to seminar committees.Video. Beside the option of streaming the video images but not saving them, two levels of recording include: (i) temporary for on-demand streaming but with an expiration date e.g., 30, 60, 90 days; and (ii) archiving for permanent storage .Capture Data and Infrastructure. The schematic in Sponsoring units would be responsible for supplying laptops and video cameras with the campus IT units responsible for software and licensing. Because full-scale implementation  of the seminar network across all 10 UC campuses will be costly, both internal and external funding sources will need to be identified. However, vetting proof-of-principle and field testing on a limited basis can be done with the existing technology and infrastructure, the results of which will help provide cost estimates and identify constraints.Figure S1Generic “consent to record” form to be signed by speakers who opt into UC seminar webcasting.(0.03 MB TIF)Click here for additional data file.Figure S2Example of a flyer for promoting departmental participation in seminar webcasting at the University of California.(3.18 MB TIF)Click here for additional data file.


We investigated cases of shigellosis in San Francisco and Alameda Counties identified during 1996 by active laboratory surveillance to assess the role of HIV infection as a risk factor for shigellosis. Dramatically elevated rates of shigellosis in HIV-infected persons implicate HIV infection as an important risk factor for shigellosis in San Francisco.


The course of alcohol consumption and cognitive dimensions of behavior change  in primary care patients are not well described. The objective of the study was to determine changes in readiness, importance and confidence after a primary care visit, and 6-month improvements in both drinking and cognitive dimensions of behavior change, in patients with unhealthy alcohol use.Prospective cohort study of patients with unhealthy alcohol use visiting primary care physicians, with repeated assessments of readiness, importance, and confidence , score range 1–10 points). Improvements 6 months later were defined as no unhealthy alcohol use or any increase in readiness, importance, or confidence. Regression models accounted for clustering by physician and adjusted for demographics, alcohol consumption and related problems, and discussion with the physician about alcohol.From before to immediately after the primary care physician visit, patients (n = 173) had increases in readiness (mean +1.0 point), importance (+0.2), and confidence (+0.5) . In adjusted models, discussion with the physician about alcohol was associated with increased readiness . At 6 months, many participants had improvements in drinking or readiness (62%), drinking or importance (58%), or drinking or confidence (56%).Readiness, importance and confidence improve in many patients with unhealthy alcohol use immediately after a primary care visit. Six months after a visit, most patients have improvements in either drinking or these cognitive dimensions of behavior change. Unhealthy alcohol use  and its consequences represent a major burden of disease in the general population ,2. AmongProcesses of change have been conceptualized in various ways; in the Transtheoretical model, Prochaska and DiClemente described the progression of individuals through stages of change . Others These three constructs can facilitate clinical conversations about health behaviors, and may even have predictive value for later behavior change -14. TheyThe predictive value of cognitive dimensions of behavior change, however, has been mixed. Demmel et al. demonstrated that in alcohol dependent inpatients, readiness accounted for 9.4% of the variance in outcome . Self-efThus, how behavior change constructs relate to later behavior change is not well understood. Furthermore, how these constructs change over time and in response to brief counseling, particularly in general healthcare settings, is also not well known. The efficacy for BI in primary care for unhealthy alcohol use is modest, and interventions with different theoretical rationales (e.g. MATCH and COMBINE studies) lead to similar results ,19,20, cWe studied a prospective cohort of adults with unhealthy alcohol use visiting an urban academic primary care practice who participated in a randomized trial of the impact of providing (or not providing) primary care physicians with patients' alcohol screening results ; physiciFor the present study, eligible patients drank risky amounts (> 14 U.S. standard drinks [12 g each]/week or > 4 drinks/occasion for men and > 7 drinks/week or > 3 drinks/occasion for women in the past month), were fluent in English or Spanish, and had data available on 3 behavior change constructs of interest. Subjects were interviewed before, immediately after the visit and 6 months later. At each time point, subjects completed 3 visual analog scales (VASs), one for each of 3 behavior constructs  ,28. SubjFor the present study, we used a continuous RTCQ score (-24 to +24) that has good reliability ,31. The Analyses were performed using SAS software 9.1.3 . P values less than 0.05 were considered to be statistically significant. All analyses controlled for clustering of subjects within physician and physician randomization group, using Generalized Estimating Equations (GEE) regression models with an exchangeable working correlation and empirical variance estimator. Of note, in the original trial, the intervention (i.e. randomization group) was not associated with improvements in drinking risky amounts.We assessed the outcomes changes in readiness, importance, and confidence between pre- and immediate post-visit assessments. Differences were computed by subtracting the pre-visit score from the immediate post-visit score. We used unadjusted models (but accounting for clustering) and models that adjusted for predictors to assess the changes between pre- and immediate post-visit assessments in each of the behavior change constructs.or readiness), importance of changing drinking (i.e. improvement in drinking or importance), or confidence in ability to change drinking (i.e. improvement in drinking or confidence). Since readiness, importance and confidence are often considered intermediate outcomes, it is of clinical relevance to use an outcome taking into account increases in these readiness to change constructs [Because a change in behavior could take place during the 6-month follow-up period after the pre-visit assessment, the state of readiness to change drinking at 6 months could become irrelevant . Therefore, to assess change outcomes, we created 3 dichotomous variables representing "improvement," each defined as either no longer drinking risky amounts or, if still drinking risky amounts, having improvement (difference > 0) in readiness to change drinking , social support (currently having a partner), alcohol consumption at study entry (drinks per day), SIP score, illicit drug use , and discussion with the physician about alcohol consumption during the visit.All analyses were repeated with the RTCQ continuous score as the outcome, in order to corroborate the results obtained with the readiness VAS.Of 4143 patients approached, 182 did not complete the screener. Of 487 who reported drinking risky amounts in the past month, 235 refused participation in the study and 18 had no time before the visit to complete the pre-visit assessment. Of the 234 remaining enrolled patients, our analytic sample was restricted to the 173 subjects drinking risky amounts who had available data on "readiness to change" at all 3 assessments . There were no significant differences (p < 0.05) between subjects included in the analytic sample and all individuals identified by screening on gender, race and readiness to change.In unadjusted analyses of visual analog scales (VASs) (score range 1 to 10 points), subjects had significant increases immediately post-visit in readiness , importance , and confidence  when compared to pre-visit assessments  reported not drinking risky amounts during 30 days prior to the 6-month follow-up interview. But most subjects had improvements in drinking or readiness, importance and confidence: 62% were no longer drinking risky amounts or had improved readiness, 58% were not drinking risky amounts or had improved importance, and 56% were not drinking risky amounts or had improved confidence. Similarly, 67% of subjects were not drinking risky amounts or had improved RTCQ-readiness. We assessed the proportion of subjects who had improved because of a change in drinking. Of the 98 subjects who had improved drinking or readiness, 54 (55%) were no longer drinking risky amounts and 44 (45%) were still drinking risky amounts but had improved readiness. For improvement in drinking or importance, 62 (62%) had improved drinking, 38 (38%) improved importance; for improvement in drinking or confidence, 62 (64%) improved drinking, 35 (36%) confidence. Results were similar for improvement in drinking or RTCQ-readiness (62 (54%) had improved drinking, 53 (46%) improved RTCQ score.In adjusted analyses, few predictors of improvement were identified. Not having a partner was a significant predictor of improvement in drinking or importance (p = 0.007), and drinking or confidence (p = 0.005). Being white was a negative predictor of improvement in drinking or readiness (p = 0.007). No other predictors were significantly associated with improvements in the hypothesized direction. Unexpectedly, having a discussion with the physician  was a negative predictor (p = 0.03) of improvement in drinking or importance Table .We assessed variations in readiness, importance and confidence regarding changing drinking after a single primary care physician visit and improvements in these constructs and drinking 6 months later. After the visit, we observed significant increases in readiness, importance, and confidence. The effects were small . However, a clinically significant change in these constructs has not yet been well-defined, and the impact of changes of any magnitude is not known. Based on the transtheoretical model and motivational interviewing, clinicians are encouraged to help patients increase motivation, which in turn is expected to lead eventually to behavior change . After aIn addition to these short-term changes, we studied the course of risky drinking and "readiness to change" in primary care patients. Six months after a physician visit, most subjects improved either their drinking or readiness. These improvements suggest that primary care physicians should be somewhat optimistic regarding the course of unhealthy alcohol use, with more than half of patients improving in a relatively short period of time.We identified few predictors of changes in "readiness to change" and none that were consistent across measures or time. Not having a partner was a positive predictor of immediate changes in readiness but a negative predictor of improvement in two measures 6 months later. Being white was associated with worse readiness immediately after a physician visit and less improvement 6 months later but the finding was not confirmed in analyses with the RTCQ or the other two behavior change construct measures. Speculation regarding the mechanism for these hypothesis generating and inconsistent findings would be premature.A discussion between the physician and the subject about alcohol predicted a positive change in readiness immediately after the visit (confirmed by the RTCQ), but paradoxically, was associated with less improvement in drinking or importance (but no change in VAS- or RTCQ-measured readiness). The fact that no association was found between discussion with the physician and drinking 6 months later may have been due to the use of ineffective counseling, but given the observed short-term effect, another explanation could be simply that this effect did not last.Neither alcohol consumption, alcohol problems, nor illicit drug use significantly affected behavior change constructs or improvements. The fact that these markers of severity were not found to be negative predictors of improvement is of interest and should encourage physicians to address problems related to alcohol consumption even in the presence of concomitant illicit drug use, considering that most of their patients will have some improvement, independent of the severity of the alcohol problem.A number of studies have assessed readiness to change and related constructs. In general, these studies have focused on characterizing specific populations ,36-39 orIn addition to the aforementioned studies of the natural history of alcohol use disorders, studies of brief intervention for nondependent unhealthy alcohol use in primary care consistently report improvement over time in both treated and untreated individuals . For exaThis study has some strengths. To our knowledge, this is the first study to explore changes in readiness, importance and confidence during a single primary care visit. We described rapid changes in these constructs. We were also able to describe changes in readiness, importance or confidence and drinking over a 6 month period. Subjects studied were participants in a trial but there was no experimental brief counseling intervention nor a significant treatment effect on drinking amounts.The study also has some limitations. First, the applicability of our findings may be limited to primary care patients with unhealthy alcohol use who agree to be screened and followed in a research study, and to those with similar characteristics as in our sample . Although participants differed little from those who did not participate, participants did drink more. Similarly, subjects lost to the analytic sample differed little from those studied except on gender. The effects of these differences can be considered in the interpretation of our results. Second, findings are from secondary data analyses. Causality (of predictors) cannot be inferred, and there could be many explanations for changes in the readiness constructs. However, observational studies such as this one are likely among the best ways to study the natural course of behavior change constructs and changes in drinking, particularly prospective studies. Third, in our attempt to explore changes over time, we had to combine actual behavior  with cognitions about behavior change. It is likely that these two dimensions reflect different aspects of behavior. We presented data on the dimensions separately (and combined) but performed regression analyses on the combined outcome. From a clinical perspective, improvements in either drinking or readiness (combined) seem to be most relevant. Also, the interpretation of a 6 month change in readiness on a continuous scale for someone who continues to drink risky amounts is difficult, since it not clear how one would interpret a change in some number of points. Fourth, we did not adjust the level of significance for multiple comparisons. As such one should be cautious about interpreting associations, particularly those not in the hypothesized direction. Lastly, all data were obtained from interviews and are subject to recall and social desirability biases. But interviews with trained research associates and assurances of confidentiality took place immediately after the primary care visit to maximize accurate recall and minimize bias. Nonetheless, we do not know what patients meant by discussions about alcohol, which could have been brief or extensive and may or may not have included known effective components of brief interventions.Our results provide important information. First, subjects appear to change readiness, importance and confidence after a single physician visit. Second, most patients with unhealthy alcohol use will improve 6 months after a primary care visit, either on behavioral change constructs or drinking. Third, factors usually associated with worse alcohol treatment outcomes  do not seem to prevent improvement. Future research should focus on specific measures of behavior change constructs, perhaps assessed by ecological momentary assessments of these rapidly changing dimensions ,48 and wThe authors declare that they have no competing interests.NB, NH, and RS conceived and designed the study. RS led implementation of the SIP study randomized trial. NH led and programmed the statistical analyses. NB wrote the first draft of the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here: