Hearing loss is the second most common chronic disease, the diagnosis and treatment of which can be faster through screening. In addition, early interventions will save significant costs for the education and health systems. Therefore, the present study aimed to evaluate the cost-effectiveness of hearing screening for primary school children in Shiraz.This cross-sectional economic evaluation of cost-effectiveness was conducted from the perspective of the health system. The study population comprised all seven-year-old children participating in the screening program in Shiraz. The present study dealt only with direct costs. The expected costs and outcomes, as well as the ICER index were estimated using the decision tree model. The study outcomes included averted disability-adjusted life years (DALY) and true identification of hearing loss cases. The robustness of the results was evaluated using the one-way sensitivity analysis. The TreeAge 2020 and Excel 2016 software were also used to analyze the collected data.The hearing screening data obtained during 6 years (2015–2020) showed that every year, an average of 22,853 children in Shiraz were examined for hearing, of which 260 were true positive (%1.1). The costs of screening and lack of screening were estimated at $30.32 Purchasing Power Parity (PPP) and $13.75 PPP per child, respectively. The averted DALY due to performing hearing screening was estimated at 7 years for each child. The ICER was positive and equal to $ 0.06 PPP for the identified cases and $ 2.37 PPP per averted DALY. The sensitivity analysis confirmed the robustness of the results.According to the results, although hearing screening for primary school children had more costs and effectiveness, it was considered cost-effective. Therefore, universal screening with high quality and accuracy is recommended. Hearing loss is the second most common chronic physical condition . HearingThe consequences of hearing loss include isolation, decreased social activities, feeling of limitation, and increased depression symptoms , 7. If hStudies have shown that development of auditory nerves requires early auditory stimulation before the age of two . The onsThe prevalence of hearing loss in different countries ranges from 0.5 to six per 1000 children . In IranEarly diagnosis and treatment of hearing loss in children are the significant benefits of the universal hearing screening program that may enable early interventions in the first years of life to enhance hearing and promote speech development , 19. It In addition to affecting the quality and development of people’s lives, hearing loss has a significant economic burden. The World Health Organization (WHO) estimated that the global cost of undiagnosed hearing loss was 750–790 billion international dollars (Int $) per year . AccordiThere is no doubt about performing Universal Newborn Hearing Screening (UNHS) and it is highly recommended , 24–26. 2, Fars is the fifth largest province in the country. The capital city of Shiraz with a length of 40 km and a width of 15 to 30 km has an area of 1268 km2. It is shaped rectangular and is geographically located in southwestern Iran and in the center of Fars province. The city has a population of about two million and is considered a medical hub in the region. The present study was conducted from the perspective of the health system and no sampling method was used. The research population included all of the children participated in the school entry screening program in 2020 in Shiraz, who were selected through census.This study is a cross-sectional economic evaluation of cost-effectiveness and retrospective research to evaluate the cost and effectiveness of two approaches, including continuity and non-conduct of the hearing screening program for the children entering primary schools in Shiraz. Located in the south of Iran, Shiraz is a metropolis and the capital of Fars province that is approximately between the 27- and 31-degree north orbits and 50- and 55-degree meridians on the east longitude. Having the area of 122,608 kmEvery year, new students are screened in 13 screening centers in Shiraz. The data of the children screened for hearing within 6 years (2015–2020) was obtained from the Department of Exceptional Education in Shiraz. Furthermore, the information of the children referred to audiologists was used to calculate the prevalence of various types of hearing therapies. To this end, a checklist containing medical information of the children referred at the screening stage was prepared and filled out. Using the results obtained from the checklist, we categorized the children who needed an audiologist or an ENT specialist to receive additional diagnostic tests and treatments.When enrolling in the first grade of primary school, Iranian children are medically examined in terms of their skin and hair, height and weight, mouth and teeth health, vision and hearing, and academic readiness. One of the services provided is audiometry. School-aged children are screened by the pure tone audiometry method. In this study, all children aged 6 to 7 years who entered the first grade of primary school in Shiraz in 2015–2020 were evaluated. The instruments used in this research were audiometers with frequencies of 500, 1000, 2000, and 4000, as well as tympanometers.Figure The true identification of hearing loss cases and averted DALY were selected as the outcomes for the hearing screening program. It was assumed that the children who were diagnosed with hearing problems after screening and were referred to an audiologist and then to an ENT specialist for further examinations were true cases of hearing loss.The disability adjusted life years (DALY) were obtained from the sum of years of life lost (YLL) and years of life disabled (YLD). The former was considered zero due to the lack of premature death from hearing loss, and the latter was calculated using the following formula: by year .https://www.who.int/countries/irn/). The disability weight for the screening strategy was calculated at 0.06 from the lower limit of the geometric mean of different disability levels (mild to severe). In the non-conduct strategy, the disability weight was calculated at 0.15 from the upper limit of the geometric mean of different levels of hearing problems (mild to severe). The upper and lower limits of the disability weight were derived from the study by Orji et al. [The DALY was calculated for the conduct of screening and non-conduct. The prevalence of hearing loss and life expectancy was the same in both strategies. The prevalence of hearing loss was 1.14, obtained by dividing the number of true identified cases (260) by the total number of screened cases  multiplied by 100  and Current  in the hearing screening program for new students were retrospectively collected for each student from the Department of Exceptional Education of Shiraz in 2020. Other costs, including those of referring the children for hearing tests and treatments, were calculated in consultation with clinical specialists and according to the 2020 tariffs. It was estimated that 70% of the people went to public and 30% to private health centers to receive services. In the present study, short-term costs were calculated based on the screening results, and long-term educational and improvement costs incurred during a person’s life  were not calculated. In addition, the costs were converted to $PPP using the exchange rate of each $PPP equal to 31,317 Rials in 2020 [The incremental cost-effectiveness ratio (ICER) was calculated using the ratio of the cost difference to effectiveness difference. The ICER showed how the costs would change with one unit of increase in effectiveness . The folThe data were analyzed using TreeAge and Excel software.Finally, the one-way sensitivity analysis was used to assess the effects of parameter uncertainty on the results. To perform the one-way sensitivity analysis, some key parameters such as cost and utility were changed by 20% for each strategy, and the results were presented in the form of a Tornado Diagram. Due to the lack of an explicit willingness to pay (WTP) threshold in Iran, and as proposed by the WHO for developing countries, the threshold was one to three times the per capita GDP . The GDPFigure n = 1559, average: 260 (1.1%)).Table n = 453, average: 75.5 (29.1%)) and the least diagnosed problems were children who had to enroll in special schools (deaf) due to hearing problems ).Accordingly, the most diagnosed problem is the number of children seeking medical treatment for their hearing problems (n = 260). The percentages presented in this table were used to calculate treatment costs.Table According to Table The other outcome of the present study was the averted DALY. Given that the YLL in this study was zero, the DALY was 4.7 in the screening strategy and 11.7 in the non-conduct. Thus, the averted DALY due to screening was 7 years.Table The hearing screening cost per primary school child in 2020 was estimated at $ 4.92.Diagnostic costs consisted of the costs of visits and tests. The referral fee in the screening program included the cost of visiting an audiologist ($ 2.21 PPP per child) and an audiometric test ($ 16.40 PPP) paid by the government. If screening was not performed, the children were referred to an audiologist ($ 6.43 PPP) by a family physician ($ 5.01 PPP) for required tests ($ 16.40 PPP) and then to a specialist ($ 9.94 PPP) for treatment. Thus, the diagnostic cost per individual would be $ 39.99 PPP. These costs were calculated based on the private and government tariffs set in 2020.The pharmacotherapy included amoxicillin and co-amoxiclav. The mean cost of drugs was calculated based on the daily consumption and treatment period. Nine common types of auditory practice were identified based on the Relative Values book and the specialists’ opinions. The mean cost of the practices was also calculated.The treatment costs of hearing screening continuation and non-screening were calculated using the percentages of different treatments obtained through the checklist of those referred to the audiologists in the 2020 screening program Table . In the According to the experts, if primary school children were not screened for hearing problems and were diagnosed late, in the worst case, those who required pharmacotherapy earlier would require hearing surgery in later stages. However, late referral for ear micro-suction and hearing aid treatments would affect the individual’s quality of life and academic achievement . Therefore, in the case of non-screening, the costs of ear micro-suction and hearing aids treatments were also considered. Regarding pharmacotherapy, surgical costs  were considered as well.The costs of hearing aids, medication, ear micro-suction, and surgery were calculated according to the percentages presented in Table The results of the cost-effectiveness analysis Figs.  and 4 shn = 260) and averted DALY(=7), but the latter had an effectiveness of zero in terms of both items. On the other hand, the cost of the screening strategy ($ 30.32 PPP) was higher than that of no-screening ($ 13.75 PPP). The ICERs calculated for the number of true positive cases and the DALY were $ 0.06 PPP and $ 2.37 PPP, respectively, indicating that the screening strategy was superior despite its positive ICER and higher cost and effectiveness, because its ICER was below the threshold.The cost-effectiveness of the screening and no-screening strategies are shown in Table In the one-way sensitivity analysis, the value of each parameter was changed by 20% and a tornado diagram was presented to identify the individual parameters with the highest and lowest sensitivities on the outcome (ICER). The tornado diagram showed that the findings of this study were more sensitive to the cost of screening and had the lowest sensitivity to the cost of no screening Figs. , 6.Fig. As stated, early diagnosis and treatment of hearing disorders to improve academic achievements and social relations are recommended in many studies. The present study aimed to compare the costs and effectiveness of the two strategies, including conducting hearing screening for primary school children and no screening. During 6 years, 22,853 primary school children were screened and on average, 260 true positive cases were identified each year. The prevalence of hearing loss in this study was 1.14, which is consistent with the WHO’s estimates of global disease burden . The stuThe results of a systematic review of previous research on the cost-effectiveness of preschool hearing screening showed that the costs presented in different studies varied significantly . SubsequFortnum et al. indicated that school entry screening (SES) was unlikely to be cost-effective unless referrals were made faster by the SES . The samOther researchers such as Diener et al. 2017) stated that targeted cytomegalovirus (CMV) screening improved early detection of hearing loss from 56 to 77%. Therefore, follow-up and evaluation of risk cases could result in more improvement. Thus, they recommended examining the children with risk factors . CMV is 017 stateThe present study did not deal with the impact of hearing loss on individuals’ quality of life. Other studies showed that hearing loss had considerable economic costs, and according to the Centers for Disease Control, the lifetime medical, educational, and occupational costs of hearing loss for the children born in 2000 were $ 2.1 billion .The results of the one-way sensitivity analysis suggested that despite the positive ICER and higher cost and effectiveness, the screening strategy was cost-effective since its ICER was below the threshold. In addition, the highest sensitivity was to the cost of screening.One limitation of this study was the lack of considering long-term educational and training costs caused by hearing loss and not addressing indirect costs when analyzing the results. Another limitation was not dealing with the inevitable effects of hearing loss on quality of life, academic achievement, career advancement, and social relations.The results of the present research and the review of similar studies indicated the importance of the identification of children with hearing disorders before the age of two. Despite the cost-effectiveness of the hearing screening program for primary school children, late detection of hearing disorders when entering school will still prevent them from normal communication and academic progress. Hearing improvement interventions after the age of two are less valuable and effective than early interventions in infancy. Therefore, it is suggested to explore and develop methods for faster detection of hearing loss before the age of two to inform parents. Future studies are suggested to examine and compare the effectiveness of hearing interventions for children at different ages.


Djaalinj Waakinj cohort study (2017–2021),Otitis media and associated hearing loss are highly prevalent in Indigenous Australian children.Djaalinj Waakinj methodology has been described in detail elsewhere.The Djaalinj Waakinj study was approved by the Western Australian Aboriginal Human Ethics Committee (WAAHEC #759) and the Child and Adolescent Health Services Human Ethics Research Committee (CAHS HREC #12).The presence of middle ear effusion was assessed using tympanometry. Findings were classified by an audiologist: type A tympanograms were deemed to indicate normal middle ear function (no otitis media), type B tympanograms probable otitis media, and type C tympanograms probable Eustachian tube dysfunction. The Sixty‐seven of the 125 enrolled infants completed formal hearing assessments ; 41 were boys (61%). Twenty‐one of the 67 infants (31%) had normal hearing, 46 (69%) had some degree of hearing loss , including 22 with mild (33%) and 24 with moderate hearing loss (36%). Mean hearing responses were poorer for the 35 infants with abnormal tympanograms at the time of hearing assessment  than for the 30 infants with normal tympanograms  .Box 1* Normal: type A tympanogram (30 infants); abnormal: type B (30 infants) or type C (five infants). Tympanograms were not available for two infants. Visual reinforcement audiometry was performed with GSI 61 (Grason–Stadler), Equinox (Interacoustics), and Avant (MedRx) audiometers, using pure tone, warble, or filtered narrowband noise stimuli through loudspeakers one metre from the child’s ear at an angle of 90°. Tympanometry was conducted using either Titan Middle Ear Analyser (Interacoustics) or GSI 39 or MI 44 tympanometers (Maico).Our finding that 69% of urban Aboriginal infants in our study had hearing loss at about twelve months of age is comparable with that of a similar study in Kalgoorlie (65%).The mean hearing response in infants with abnormal tympanograms was 40.7 dB, a level at which they would not hear normal voices clearly, with implications for later speech, language, and behavioural development.Open access publishing facilitated by The University of Western Australia, as part of the Wiley ‐ The University of Western Australia agreement via the Council of Australian University Librarians.No relevant disclosures.


Flavones  also showed 25–37% reduction in HUVECs migration at 10 µM. In a Western blotting assay, 5a and 5b subdued VEGFR2 phosphorylation by 37% and 57%, respectively, suggesting that VEGFR2 may be their main antiangiogenic target. 5b displayed the best docking fit with VEGFR2 in an in silico study, followed by 5a, emphasizing the importance of the 7-hydroxyl group accompanied by a 4−C=S for activity. Conversely, derivatives with a 4-carbonyl moiety fitted poorly into the target’s binding pocket, suggesting that their antiangiogenic activity depends on a different target. This study provides valuable insight into the Structure Activity Relationships (SAR) and modes of action of halogenated flavones with VEGFR2 and highlights their therapeutic potential as antiangiogenic/anticancer lead compounds.Antiangiogenic agents attenuate tumours’ growth and metastases and are therefore beneficial as an adjuvant or standalone cancer regimen. Drugs with dual antiproliferative and antiangiogenic activities can achieve anticancer efficacy and overcome acquired resistance. In this study, synthetic flavones ( Vessel formation is essential for early organogenesis, and maintaining the normal body growth and function that follow . VasculoTumours rely heavily on an increased blood supply due to their aggravated need for oxygen and nutrients. In that context, angiogenesis is promoted during the early stages of tumour development and plays a key part in cancer metastases ,9. TumouDespite the perceived success of antiangiogenic agents in prolonging progression-free survival rates among cancer patients, their impact on overall survival was limited . The dowFlavonoids are one of the most extensively studied chemical classes of compounds for their general therapeutic effects owing to their abundance in nature and versatile pharmacological activities that include their anticancer, anti-inflammatory, neuroprotective and cardioprotective profiles ,22. Ther5a,b) that showed promising antiproliferative and growth inhibitory activities against several cancer cell lines  = 4.9 and 1 µM, respectively; NCI GI50 against MCF-7 = 1.46 µM and 0.18 µM, respectively) in our previous report pyrimidine was extracted from the coordinate file of the VEGFR2 receptor (1YWN). The protomol, representing the ligand-binding groove, was generated using a ligand-directed method, which allows for the docking of ligands into predefined sites, as defined by occupancy of any co-crystallised ligand at the site of interest. The Surflex-X docking algorithm docks a given ligand to a receptor using a flexible ligand and a semi-flexible receptor algorithm; in this case, the compounds were allowed to be fully flexible while the receptor was semi-flexible. This allows for the optimisation of potentially favourable molecular interactions, such as those defined by hydrogen bond and van der Waal forces. The docking results yield a docking score, which takes into consideration entropic, polar, hydrophobic, repulsive and desolvation factors. The docking scores are expressed in −log10 (Kd) units to represent binding affinities, where Kd is the dissociation constant. The free energy of binding of the ligand to the protein was extrapolated from the equation:The protein structure was prepared for docking using the Biopolymer Structure Preparation Tool with the implemented default settings provided in the SYBYL programme suite. Hydrogens were added to the protein structure in idealised geometries, and an overall energy minimisation of the protein was performed using the MMFF94 force field, employing a conjugate gradient algorithm  with a cVisualisation and analyses of the docking results as well as the molecular interactions of the docked ligands was performed using the program Maestro . Potenti3a,b–6a,b) was evaluated, in vitro. Analysis of the findings of the different assays used suggested that structural modifications among the tested panel impacted their antiangiogenic behaviour and mode of action. While compounds with a 4-thiocarbonyl functionality demonstrated a dose-dependant and generally higher tube formation inhibition activity, their 4-carbonyl counterparts showed a concentration independent pattern of antiangiogenic activity. Meanwhile, the four most active compounds  showed comparable levels of tube formation inhibition  to that of the antiangiogenic drug sunitinib . Besides the VEGFR2 docking study, comparison of the results of the different assays used here, i.e., tube formation, migration and VEGFR2 phosphorylation activation, provided more insight into the antiangiogenic SAR of the candidate flavones. Evidently, compounds 5a,b possessing 7-OH and 4-C=S groups mainly depend on VEGFR2 inhibition to mediate their observed antiangiogenic effects. In that regard, an additional OH group at position 5 resulted in higher binding affinity with VEGFR2, which translated into 5b being more active. On the other hand, 5b’s 5,7-dimethoxy analogue (4b) reliance on VEGFR2 interaction was at a much lower level. As for the flavone 6a, no association was found between its antiangiogenic reactivity and VEGFR2. Further investigation of the docking poses of 6a and other flavones with 4-C=O  with VEGFR2 showcased the negative impact of the carbonyl group on molecular interactions with the receptor. All in all, this study presented four potential antiangiogenic lead compounds  and provided important perspectives on their possible mechanisms of action and SAR. These lead compounds are excellent candidates for future structural modifications and further antiangiogenic and anticancer evaluation especially since thioflavones  have previously exhibited promising anticancer activity in vitro [In this study, the antiangiogenic potential of two series of structurally similar halogenated flavone derivatives (in vitro .


Future Home of the Living God (2017) by Louise Erdrich (Ojibwe). Written over the course of two reinstatements of the Mexico City Policy, Erdrich’s novel invites a consideration of biocolonialism in relation to the exploitation and policing of female bodies.This article argues that the health humanities must examine biocolonialism (and representations thereof) if it is to attend to Native American experiences of reproductive healthcare in the USA. Reproductive healthcare abuses are brought into dialogue with Native American resistance to Western biomedical sciences in After a discussion of bioprospecting and female bodies, I frame unethical practices of reproductive healthcare and sterilisation as biocolonial acts. The experience of the novel’s protagonist, Cedar Hawk Songmaker, will be situated alongside the broader ways in which Native Americans are subjected to surveillance. Second, this article proposes that speculative fiction allows for a temporal reframing of the colonial histories of Indigenous healthcare. As she narrates a world in which evolution ‘is running backward’, Cedar employs narrative reversals to resist the linear narrative of progress and ‘discovery’ associated with biomedical sciences.The radically changing structures of a dystopian state, as well as the revelation of her biological inheritance, complicate the cultural and medical frameworks within which Cedar narrates her pregnancy. A challenge faced by the health humanities is how the discipline might theorise ongoing, interrelated forms of domination such as those which position female Indigenous bodies as ‘new colonies’. But, as I will argue, the mobilisation of Indigenous narrative forms and cultural frameworks offer productive directions for future work within the global health humanities. As the health humanities extends the cultural and theoretical vantage points from which it critiques medical practice , and adoSuch anxieties have, in turn, become common tropes in speculative fiction, a genre that frequently depicts fertility crises in order to question the survival of future populations.Future Home of the Living God, a novel which charts the course of a Cedar Hawk Songmaker’s pregnancy amidst a global ‘biological confusion’  draws together reproductive healthcare abuses and Native American resistance to biocolonialism in nfusion’ 5.4 As gFuture Home. A similar disjuncture between Erdrich and her representations of Indigeneity can be gleaned from initial reviews of the novel , Cedar employs narrative reversals to resist the overwhelmingly linear narrative of progress and ‘discovery’ associated with biomedical sciences. This reframing, which aligns with Indigenous conceptualisations of time, renders visible the relationship between biocolonialism and other forms of coloniality.Erdrich’s foray into speculative fiction has been regarded as an experimental break from her earlier work, a ‘striking departure’ from other novels about Native American communities in North Dakota . Yet frahe novel , which hd’s Tale . As a fiom them’ , comes aom them’ 81 priorom them’ , 210, thFuture Home as specifically biocolonial is enabled through the ways in which fundamental critiques of extraction, ownership and commodification have been applied to the site of female bodies  unaffected by the evolutionary crisis.To consider a dystopian novel about an international infertility crisis might, at first, seem at odds with the more established use of ‘biocolonialism’ as a form of oppression. But I would argue that the issues presented by Erdrich align with Laurelyn Whitt’s explanation of the ‘diverse forms of extractive biocolonialism’ in which ‘valued genetic resources and information are actively sought, ‘discovered’, and removed to the microworlds of biotechnoscience’ 33. OnceAlongside research on biocolonialism within Native North America, Vandana Shiva’s research on biopiracy considers how ‘new colonies are being carved out’ on a global scale:Capital now has to look for new colonies to invade and exploit for its further accumulation. These new colonies are, in my view, the interior spaces of the bodies of women, plants, and animals. 5According to Shiva, reproductive healthcare and pregnancy should be understood as aspects of Indigenous life which are vulnerable to biocolonial exploitation. This projection of what, or who, will be targeted as ‘new colonies’ is combined with Whitt’s theorisations of extractive biocolonialism by Susan Hawthorne. Her examination of the extractive acts of biopiracy directly suggests that abuses in reproductive healthcare fall under the purview of biocolonial practices. Female bodies and Indigenous peoples, Hawthorne argues, have been colonised in ways analogous to the colonisation of land.The mining of women’s body parts is routine and is especially widespread among those engaged in reproductive technologies and stem-cell and cloning research using the by-products of abortions. […] These latest assaults are an extension of the same philosophy. Women’s bodies are resources and a major site of colonization and profit making. 318–19 5terra nullius principle which has historically ‘justified’ settler colonial occupation of ‘empty’ land and the fact that women’s bodies are ‘viewed as inert, passive and empty, that is, ripe for exploitation’  are not eligible to receive US federal funding if they use their own funding (or that of third parties) to provide access to abortions or abortion-related services, including counselling and education. The policy’s restrictions ‘effectively preclude such NGOs from providing safe abortion services even where it is legal in their own countries for indications not covered by the Gag’ , was first enacted by President Ronald Regan in 1984. The policy, though rescinded by the Clinton and Obama administrations, has been reinstated by every Republican president. Trump’s expansion of the policy—renamed ‘Protecting Life in Global Health Assistance’—escalated the restrictions to all ‘global health assistance furnished by all [US] departments or agencies' , 8495, aWith such stark consequences for public health, the policy has been increasingly critiqued within anticolonial and global health discourse. No evidence has suggested that the number of abortions has reduced in countries where the Global Gag Rule is in effect. Rather, the limited available evidence collated by Jeffrey B. Bingenheimer and Patty Skuster suggests that the rule leads to an increase in abortions carried out, an increase in maternal mortality and negative child health outcomes 280–82. Where the Global Gag Rule, ‘America’s deadly export’ , undermiFuture Home, though they often give rise to newly adapted health policies, they are also catalysts for new forms of stigma and new opportunities to demarcate or marginalise difference. Indeed, the ongoing COVID-19 pandemic exemplifies Reagan’s observations and highlights the urgent need for analytical practices employed by critics, including Barrish, that foreground the wider repercussions of health policy during times of global health crises.Following the approach of Phillip Barrish, who argues that health humanities ought to address what he has termed ‘health policy fiction’, I have outlined the effects and implications of these policies on reproductive health because healthcare is ‘a complex set of financial models, public and private institutions, government policies, and actors whose roles range well beyond patient and care provider’ 297. EpiErdrich’s speculative text presents the literary ‘afterlives’ of these health policies, and the colonial logics they uphold, by bringing together multifaceted concerns of inheritance and legacy in this time of a collective fertility crisis. To resist the new policies of surveillance and sequestration enforced by the Church of the New Constitution, Cedar goes into hiding, but not before establishing contact with her biological parents. As an ‘adopted child of Minneapolis liberals’ (3), Cedar Hawk Songmaker has only engaged with her Ojibwe identity in a limited way, regarding herself as a ‘theoretical Native’ (4).I wouldn’t have had the slightest thing to do with them if it wasn’t for my baby. […] You deserve more. You deserve two sets of grandparents. Not to mention genetic info, which may affect who you are even beyond whatever is now occurring. There may be hereditary illnesses. (6)Concerned exclusively with the genetic information, rather than Native ‘culture’, that the baby might inherit from their ‘bio-based grandparents’ (4), Cedar’s actions and priorities mirror those of the state, which foregrounds biogenetic security and fetal health above all else. The biological and reproductive continuance of the general population motivates new totalitarian measures at the expense of other aspects of cultural and social welfare. But the apprehension surrounding hereditary illnesses within Cedar’s biological family is conflated with a wider biogenetic threat faced by her unborn child. While this concern might seem futile within the wider context of a global pandemic, the determination to establish the health of her child at the level of individual inheritance parallels the purpose and function of her construction of a written record of the pandemic for an individual reader.about rather than experience directly).Throughout the diary, Cedar figuratively constructs her child as a reader. This is primarily achieved by narrativising stages of fetal development with second person pronouns: ‘your brain is hooked up to stereo – your ears. […] You can hear me as I read aloud the first words of my letter to you’ (63). Although Cedar is aware that constructing this narrative is of limited use in such turbulent times, addressing her prenatal reader becomes, in this state of uncertainty, an important means of willing her baby’s survival and the hoped-for end of the evolutionary pandemic. Unsure of the baby’s health during this crisis, Cedar imaginatively creates a healthy reader who, years later, is able to read their mother’s diary. As observed, however, within Rebekah Sheldon’s comprehensive analysis of the child figure in ‘sterility apocalypses’, a ‘conjunction of the child with the future is never clean, […] because the child is not a guarantee of replication’ 35. ThisThe refuge that Cedar, as narrator of her child’s future health, accesses through writing outlives her physical safety once her pregnancy is made known to the Church of the New Constitution. Phil, the father of her child, is arrested and tortured by ministers during a ‘truth seminar’ (191) before revealing Cedar’s location. Captured by the Unborn Protection Society, an organisation tasked with tracing and detaining pregnant women (and which have repurposed the United Parcel Service’s vehicles), Cedar is taken to Fairview Riverside Hospital to ‘give birth under controlled circumstances’ (72). It is in this setting that Cedar’s body is most fully treated as a ‘new colony’ 5; patieIt is clear that our fluids, as taken from us and used for evaluative purposes, are unpredictable and leaky. They become useful to others – organisations, the state, and forms of governmentality – and then are made to tell certain kinds of biopolitical truths about our bodies. […] Our bodies are no longer seen to matter as individual lives, but, rather, our fluids and tissues taken together represent a kind of environmental aggregate that speaks volumes about the future of our species on the planet. 118Tellingly, Casper and Moore are aware that such practices hardly seem believable: ‘These parts, then, as if in some science fiction dystopia, achieve a monstrous power over us in the form of numeric codes’ 118. It is indeed white—complicates a reading of the novel that would seek to clearly distinguish between the dominant and oppressed group(s) within whose relationship of dominance such biocolonialism might occur.Moreover, the underlying threat that Cedar may not keep her child, having heard the rumours that hospitals keep surviving babies, reflects the structures of institutional and private ownership which enable biocolonial acts to occur. Indigenous knowledge and biological material are converted into private property by the dominant culture to maintain a relationship of colonial control over Indigenous peoples 23. UndoDespite Cedar’s position as an adoptee who can pass as white, racialisation does occur within clinical settings during her pregnancy, entangling the dual structures of race and reproductive capability which now demarcate the population under the Church of the New Constitution. Processes of racialisation and racial discrimination are less overt than the imprisonment of pregnant women or conscription of ‘Womb Volunteers’, yet fragments of information, documented within Cedar’s diary, suggest that white superiority is reinforced during this crisis. Cedar receives such information from a doctor-turned-informant during an appointment in the early stages of her pregnancy. At first, this ultrasound scan is indicative of the coercive or non-consensual clinical encounters faced by every pregnant woman under the regime. Technicians ignore Cedar’s questions as they measure the fetal skull, vertebrae and limbs. The ostensible viability of her pregnancy, ‘evidenced’ by the doctor’s interpretation of these measurements, means Cedar will not be allowed to leave the clinic of her own volition; medical institutions must now sequester and monitor every woman displaying signs of a ‘normal’ pregnancy. When left alone with Cedar, however, the unnamed doctor instructs her to restrain him and escape. Before the doctor is voluntarily gagged, he asks if Cedar has ‘any special ethnicity’ (51).‘Yeah, I’m Ojibwe,’ I tell him.He asks me about the father, is he white?‘As milk,’ I said.‘Then get the hell out of here. […] When you get out, don’t tell anybody that you’re pregnant.’ (51)Future Home of a child of Indigenous and white parentage aligns with longer histories of forced child removal and cultural assimilation in settler colonial contexts which privilege whiteness. Given the restricted narrative perspective and limited information Cedar can access, readers cannot know the full extent to which whiteness is privileged by the Church of the New Constitution, or how this clinical encounter would unfold for prospective parents of other races or ethnicities. But the doctor’s implication that Cedar is in urgent danger, as a white-coded pregnant woman carrying the child of a white father, affirms the white supremacist logics on which forms of biocolonial extraction are predicated.Even as she is in the very process of escaping, the doctor emphatically instructs Cedar to ‘get the hell out of here’ once he learns that the child’s father is white. This would suggest that race is a contributing factor in how the regime assigns value to the pregnancies it monitors and, more broadly, confirms Brianna Theobald’s argument that, for Indigenous women, ‘reproductive politics cannot be disentangled from the structures of white supremacy and capitalism’ 222. IndWith the ensuing panic surrounding the future of the population—specifically, the white population—a ‘desperate market’, to use Rachel Stein’s phrase, might materialise in relation to the increasing value of pregnant bodies and others who could carry viable fetuses 104. In Towards the end of the novel, the value placed on Cedar’s unborn child appears to increase. Once she is reunited with Phil, Cedar learns that she is now classified as ‘carrying one of the originals’ (245). In other words, given the time of conception, her baby might not be affected by the evolutionary crisis. When combined with their highly prized ethnicity (as divulged by the informant doctor), the ‘originary’ status of the baby apparently carries significant monetary value.‘The thing is,’ he says, very softly, ‘you have a treasure, Cedar, if our baby is normal. We could be in charge of things. Rich. Super rich! We’d be safe. If we somehow worked out genetically, I mean, to have a normal child the sky’s the limit for us.’‘We could seize power and found a dynasty,’ I say, meaning it sarcastically.‘That’s right,’ says Phil softly, reaching for me. I bat away his hand and call Eddy. (246-247)Phil’s speculation suggests that a political elite has emerged based on reproductive capability, infant survival rates and a biomedicalisation of normalcy. Where Cedar’s sarcasm is explicit, Phil’s motives are less easy to ascertain as he reaches for the mother of his child, the carrier of a potential source of wealth and prosperity required to survive within this regime. Cedar’s narration of the conversation within her diary hints towards a desire to capitalise on the ‘normality’ of their child and the privilege it would afford him. The extent to which this can be framed as biocolonial, in systemic terms, is obfuscated by Phil’s relationship to his unborn child and the hypothetical nature of the conversation. Nevertheless, Cedar instinctively remains ‘alert to something bad beneath his words’ (246) as Phil imaginatively places himself within the elite group. In this way, the future that Phil imagines upholds the commodification of profitable pregnant bodies, alongside the ostensible value placed by the state on whiteness and normalcy.Future Home allows for biocolonial practices to occur within reproductive and antenatal healthcare. In this section, I explore how Erdrich’s deployment of the speculative genre allows for a temporal reframing of colonial histories as they relate to reproductive healthcare. Sheldon has similarly forged interpretative associations between the temporally disjointed figure of the child in speculative fiction, and the genre’s potential for ‘textual reproductions’: encompassing depictions of birth and the narrative mechanisms by which futurities are made possible through a ‘novel’s structural rejection of reproduction’ , the Songmakers agreed to raise Cedar under the guise of a full adoption. Cedar’s body physically reacts to the revelation, but not before her narrative voice immediately states, ‘What a weird reversal. Impossible to take that in’ (232). Despite Cedar’s previous embrace of her adoptive identity and multifaceted heritage, she frames these ‘sudden reversals in (her) own narrative’ (238) as a loss: ‘If that’s true, if you kept that from me, I could have had my real father all my life.’ (233).Contrary to the control exerted over her body and pregnancy, moments where Cedar faces intense danger are often entries within the diary where she displays the most agency as a narrator. Erdrich pairs the evolutionary reversals with the withdrawal of reproductive freedoms, and with reversals in the story-telling process itself. Condensed across a few diary excerpts, reversals are enacted across these three facets in Future Home within a body of literature which complicates the dominant paradigms through which we culturally understand adoption practices After the 20 November entry, the subsequent Thanksgiving entry (one of the few chapters without a precise date) calls into question what the reader has just been told. Moments of confusion are expanded, exposing the full extent to which the reader is dependent on and perhaps manipulated by Cedar’s narrative.There never was a raid. Mother did not come back. Perhaps I hallucinated her. And maybe, let’s hope, in the throes of eighth month’s hormones I hallucinated Phil. But no, Phil was out the door once I called Eddy. (247)A justification for this reversal of narrative events is never given, but two related reasons arise. First, this demonstrates Cedar’s agency over the narrative as a ‘fully empowered’ narrator of a dystopian text who has control solely over the shape of their story 176. Exareversal, dream-like scenarios, simultaneity, [and] counter-factuality’ as examples of how spiralling time might be experienced  offer a means of resisting colonial oppression given, as Whyte observes, their relation to Indigenous knowledges.Kyle P. Whyte (Potawatomi) has researched Indigenous dystopian fiction in relation to climate crises. He shares knowledge passed to him from Anishinaabe elders of ‘intergenerational time’ and ‘spiralling temporalities’ 228. Sucerienced 229. FutThe mutability of unfixed threads of narrative across the diary’s Thanksgiving entries resonates with the story of Cedar’s adoption, as well as the literal function of the unravelled and rewoven thread that had facilitated Cedar’s escape from the prison-hospital. Writing of transcultural adoption memoirs, John McLeod finds examples of adoption stories which ‘chang[e] their ending so that surprises lurk up ahead’, mirroring the continual flux of belonging and interstitial space of racial identification between self, family and the world 229. NotReturning to how the novel references the colonial exploitation of Native American women and unethical abuses of reproductive healthcare reveals another sustained mobilisation of this reversal motif. Erdrich notably modifies how the theme of reversal has generally been deployed by other Indigenous writers who expose white anxieties of loss and assert plural sovereignties via ‘the reversal of trajectories of oppression’ 325. As Rebecca M. Kluchin’s enquiry into neo-eugenic policies during the 1960s and 1970s finds that, in the USA, women of colour ‘struggled to resist coercive sterilization’ 8. GuideThe 1976 Indian Healthcare Improvement Act saw greater Native participation within and control over IHS facilities. This, together with regulations introduced in 1979 by the Department of Health, Education and Welfare designed to prevent coercive sterilisations, did bring about a reduction in sterilisation abuse . More diFuture Home’s concluding sections. Despite previous evasions of state authorities, a heavily pregnant Cedar is kidnapped and confined in a prison that has been converted, even if in name only, into a ‘birthing centre’:Erdrich’s most effective thematic ‘reversal’ of these widespread sterilisations appears in A sign above the entrance says Stillwater Birthing Center, but it is only a painted piece of canvas that covers Minnesota Correctional Facility Stillwater. (249)It is within this institution that Erdrich portrays the full scale and violence of institutionalised biocolonialism as it might relate to pregnant women of colour. Women are cyclically inseminated and forced into pregnancy, with one inmate currently ‘carrying baby number three’ (252). When detainees use hunger strikes as a non-violent mode of protest, force-feeding methods are deployed by guards. Among women ‘of every colouring and age’, Cedar is racialised as a Native American woman in Stillwater Birthing Centre because she was captured in possession of her newly acquired form of identification. On the one hand, Cedar—now ‘Mary Potts with a tribal ID’ (249)—can evade detection for the crimes she committed to escape from the hospital . Yet, that she is institutionally recognised as a minority subject now reinforces a biocolonial reading of her treatment within the birthing centre. Mandatory viewing during ‘Watching Hour’ (254) of religious propaganda purports that the women are only sentenced for the duration of a single pregnancy. Cedar firmly believes, however, that she will be imprisoned for longer: ‘Nobody gets out of here in 9 months. I’m positive. Nobody gets out of here at all’ (255). Once her baby is born, Cedar is rendered unconscious and the child is removed from her arms. From there, the health and the whereabouts of Cedar’s child is never known. As the shortest entries of her diary, two lines describe the end of December and the entire month of January: ‘Extremely weak. But still here’; ‘They say my heart is damaged’ (265). When her diary resumes in more detail, readers are told that Cedar awaits her ‘next pregnancy’ (266), the implication being that—because she has survived labour—she is a viable candidate for further inseminations. Given this continued confinement and the generic limitations of this epistolary narrative, Cedar cannot provide an account of her freedom, or the resolution of this ‘biological confusion’ (5). Although Cedar is able to imaginatively reconstruct and archive memories from a time before the crisis took hold in this diary, Erdrich’s narrative ends in a way that maintains biocolonial abuses within reproductive healthcare as a continuing phenomenon.Future Home, ‘Indians have been adapting since before 1492’ (28). Working within a speculative genre which allows for a temporal reframing of colonial oppression, Erdrich presents a dystopian society that seems to be a fictionalised future but is in fact a biocolonial rendering of the historical and ongoing injustices experienced by Native American women. Like Erdrich’s characters, our methods of reading ‘health policy fiction’ (Future Home’s interwoven concerns; the mobilisation of Indigenous narrative forms within Future Home offers productive directions for future work within the global health humanities and invites future analysis of Indigenous literatures.A challenge faced by the health humanities is how the discipline might theorise and critique ongoing, interrelated forms of domination such as those which position female Indigenous bodies as ‘new colonies’ . If critfiction’ , of theoFuture Home is not as fictionalised as it would first appear, it would follow Sisk’s line of thought to consider how Erdrich’s novel sheds light on practices in reproductive healthcare and restrictive policies which continue to constrain the reproductive freedoms of Native American women. While alternatives to regimes such as the Church of the New Constitution are not imagined in their entirety within Future Home, Cedar’s narrative certainly presents strategies which dismantle and undermine the oppressive and inequitable medical realities currently experienced by Native American women.As if this were not already an urgent task, the nexus between health, bodily autonomy, settler colonial governance and Indigenous sovereignty as exposed by the COVID-19 pandemic surely points to this necessary undertaking.


Data were compared at baseline and at 12-month post-implantation with a bone conduction hearing implant. Results: Patients demonstrated a clinically relevant mean utility gain of 0.145 following implantation and clinically relevant mean improvement in global speech spatial and qualities of hearing score following implantation. Conclusions: Bone conduction implantation was found to improve hearing and health-related quality of life and reduce hearing disability in a small cohort of patients with chronic otitis media. These data highlight the importance of providing appropriate hearing rehabilitation for individuals with chronic otitis media.Background: Chronic otitis media is a major public health burden that can result in a disabling hearing loss. Bone conduction hearing implants are an accepted form of hearing rehabilitation in these patients, but evidence supporting their usage typically comes from studies investigating mixed indications. The objective of our study was to examine how these devices impact health-related quality of life and hearing-disability in adult patients suffering from chronic otitis media. Methods: Health Utilities Index-mark III ( Chronic otitis media (COM) is an umbrella term that describes recurrent infection of the middle ear space and/or mastoid air cells, often leading to tympanic membrane perforation . The disNo current evidence-based approach to hearing rehabilitation has gained clinical consensus, but commonly performed middle ear surgeries do not always lead to satisfactory hearing outcomes  and boneAlongside traditional clinical outcome measures, there has been an increasing need to complement these with additional measures that can capture how interventions impact patients’ HRQoL. Two widely used instruments are the Health Utilities Index Mark 3 (HUI-3)  and the In this study, we use HUI-3 and SSQ data collected as part of a voluntary registry study to determine the influence that bone conduction implants have on health-related quality of life in patients with COM, with or without cholesteatoma. Health-related quality of life data collected via HUI-3 will inform optimal care in this patient group and is a step towards reducing the global burden of hearing loss. These data can also be used to generate quality-adjusted life years, which can be used to inform cost-effectiveness models, permitting comparisons capable of supporting value-based healthcare.ClinicalTrials.gov Identifier: NCT02004353). IROS is a prospective, repeated measures, longitudinal study with intra-subject controls that uses subjective evaluation tools, including the HUI-3 and SSQ, to assess patient-related benefits following the treatment of permanent hearing loss with implantable hearing devices, including bone conduction hearing aids. All sites were required to obtain ethics committee approval prior to recruitment and no applications for ethical approval were rejected.Data were collected as part of the study “Observation of Benefits for Patients Implanted with a Hearing Implant of the Company Cochlear (IROS)” (n = 26) or cholesteatoma (n = 18). For HUI-3, baseline and follow-up data were available for 10 patients. For SSQ, baseline and follow-up data were also available for six of these patients with complete HUI-3 data. All patients were implanted unilaterally. Three patients received a percutaneous Baha® Connect system and the seven remaining patients received the transcutaneous Baha Attract System.The registry contained baseline demographic and health outcomes data for 348 patients implanted with a bone conduction device and 12-month follow-up data, post implantation, for 76 patients implanted with a bone conduction device. Of these, 44/76 patients received a diagnosis of COM , where 0.2, 0.5, and 0.8 represent small, medium, and large effect sizes, respectively [Descriptive statistics are presented as means with standard deviations and one-tailed ectively . Unlike A change in overall HUI-3 HRQoL score of 0.03 is considered clinically important and changes in single attribute scores of at least 0.03–0.05 have been shown to be clinically relevant ,25. RegaTen patients with COM, with or without cholesteatoma, completed the HUI-3 pre-implantation and ten of these individuals completed the questionnaire at 12-month follow-up, post-implantation. Regarding SSQ, six patients with COM, with or without cholesteatoma, completed the SSQ pre-implantation and six of these completed the questionnaire at 12-month follow-up, post-implantation. Demographic information and pre-implantation bone conduction hearing thresholds for each group used in the analysis are presented in The HUI-3 dataset consisted of baseline and 12-month follow-up data from ten patients. The SSQ dataset consisted of baseline and 12-month follow-up data from six of these patients. There were no missing questionnaire responses in the HUI-3 data. There were six questionnaire responses missing at random throughout the SSQ, representing less than 1% of the dataset, and these were replaced with the mean score of the subscale in which data were missing.n = 10), are presented in HUI-3 scores pre-implantation and at 12-month follow up, post-implantation (n = 6) are presented. Mean speech domain scores improved from 4.36 (2.36) to 5.97 (0.97) between baseline and 12-month follow up (p = 0.052) and the effect size was large (d = 0.892). Mean spatial domain scores improved from 4.45 (2.33) to 6.41 (1.42) between baseline and 12-month follow up (p = 0.027) and the effect size was large (d = 1.012). Mean qualities of hearing domain scores improved from 5.22 (1.67) to 6.63 (1.40) between baseline and 12-month follow up (p = 0.034) and the effect size was large (d = 0.921). Finally, mean global SSQ scores improved from 4.70 (1.98) to 6.35 (1.26) between baseline and 12-month follow up (p = 0.033), and the effect size was large (d = 0.994).SSQ results between pre-implantation and 12-month follow-up  . BetweenThe primary strength of this study is that it provides HRQoL data that are specific for patients with COM undergoing implantation with bone conduction hearing devices. The study also provides information on hearing disability faced by patients with COM in their daily lives via the SSQ. However, these data are derived from a single-arm study conducted on a small sample of patients, which limits the strength of evidence. There may also be bias from loss to follow-up, since reasons for missed follow-ups were not captured. However, as the effect size is independent of sample size, it is clear that the intervention resulted in an impactful change for patients, post-implantation. However, Cohen’s d may overestimate effect size due to bias of standard deviation in small samples, and as effect size is rarely reported in otology research it is difficult to put the magnitude of these changes into perspective. Studies implementing stronger study designs and more thorough reporting and that are less susceptible to bias, such as randomized controlled trials, investigating the influence that various hearing interventions have on patients with COM are therefore warranted to strengthen the current evidence base and measures of effect size. Additionally, as HRQoL and hearing disability are known to be differentially impacted by the degree and type of hearing loss , it willMean HUI-3 and SSQ scores improved for patients with COM who underwent bone conduction hearing device implantation. Bone conduction implantation was found to improve hearing and HRQoL for patients with COM, with or without cholesteatoma, resulting in a mean utility gain of 0.145 between pre-implantation and 12-month follow-up, post implantation. This information demonstrates the importance of providing appropriate hearing rehabilitation for individuals with COM to improve the influence their hearing deficit places on their daily life. Data also demonstrate the potential for implantable hearing devices in alleviating the public health burden of COM-related hearing loss.


Surgery for vestibular schwannoma includes various techniques such as the middle cranial fossa, suboccipital, translabyrinthine, and retrolabyrinthine approaches. The retrolabyrinthine approach does not impair the labyrinth and allows postoperative hearing preservation. Previously, we reported an endoscope-assisted retrolabyrinthine approach under reinforced continuous intraoperative monitoring for preservation of hearing and facial nerve function. However, the hearing preservation rate was relatively low in patients with long-wave V latency in the auditory brainstem response or poor otoacoustic emission response under this approach. Thus, the hearing preservation rate in such patients remains to be improved. To overcome this limitation, we modified the previous approach. In 26 of the 33 consecutive cases (79%) over the last three years, preservation of hearing equivalent to that before surgery or improved hearing was achieved. Postoperative deafness was observed in only two of the 33 cases (6%). According to previous reports, the rate of hearing preservation using the retrolabyrinthine approach is approximately 30–50%. Therefore, we have achieved a higher hearing preservation rate than that previously reported using the endoscopy-assisted retrolabyrinthine approach under reinforced continuous intraoperative monitoring. These improvements in our department are considered to be helpful for hearing preservation. Vestibular schwannoma is a benign tumor originating from the Schwann cells of the auditory nerve, especially the inferior vestibular nerve . Tumors Although tumor growth can impair a patient’s hearing, it is possible to preserve hearing with several treatment modalities, including surgical resection and radiation therapy, before significant damage is caused to the auditory or facial nerves. Unfortunately, the treatment of vestibular schwannoma itself can cause hearing loss. Therefore, because of the potential side effects of treatment and the fact that the tumor is benign and non-invasive, a “wait and scan” policy may be chosen, especially for patients without hearing loss or facial nerve palsy.Surgery for vestibular schwannoma includes various techniques such as the middle cranial fossa, suboccipital, translabyrinthine, and retrolabyrinthine approaches. Surgical interventions for vestibular schwannomas can be categorized into two types: non-hearing preservation surgery and hearing preservation surgery. Most non-hearing preservation surgeries are performed using the translabyrinthine approach . The traIf hearing preservation surgery is selected, preservation of hearing should be the central focus of the procedure. Moreover, irrespective of the surgical category, surgeons must attempt to prevent facial nerve palsy, particularly in cases with no evident preoperative deficit. Therefore, intraoperative neural monitoring is widely used to assess postoperative hearing deficits and facial nerve function.In our department, we have established an endoscope-assisted retrolabyrinthine approach under reinforced continuous intraoperative monitoring for hearing preservation and facial nerve function ,7. The rPreviously, the hearing preservation rate was relatively low in patients with long auditory brainstem (ABR) wave V latency or poor otoacoustic emission (OAE) response using the endoscope-assisted retrolabyrinthine approach under reinforced continuous intraoperative monitoring . In contTo overcome this limitation, we modified the previous approach . In thisCases were recruited from Keio University Hospital, and a single surgeon performed all surgical procedures. Based on our previous study, patients without elongation of ABR wave V latency or with accompanying high OAE responses were diagnosed as good surgical candidates . In contPatients with vestibular schwannoma who underwent retrolabyrinthine surgery between April 2019 and June 2022 were enrolled (N = 33). All 33 patients underwent reinforced continuous intraoperative monitoring with FREMAP and DNAP to monitor facial nerve function and preserve hearing.(1)Pre- and postoperative hearing function (including pure tone audiometry and speech audiometry) and preoperative OAE and ABR. Pre- and postoperative hearing function was assessed using a standardized scattergram format. Postoperative hearing function was assessed at three months after surgery. For the present analyses, hearing preservation was defined as a postoperative decrease of ≤20 dB on pure tone audiometry and ≤20% on speech audiometry, as previously reported .(2)The degree of tumor resection was defined as follows: (i) total resection: tumor completely resected except the capsule; (ii) near total resection: >95% resection; (iii) subtotal resection: >90% resection; and (iv) partial resection: <90% resection ,14,15.The following parameters were examined: The surgeon attempted to maintain the ABR waveform and DNAP amplitude at >40% of the initial measurement throughout the surgery. If the amplitude decreased during the tumor resection, the surgeon stopped the procedure or selected an alternative resection route. After recovery of the amplitude, the tumor resection was continued. An example of intraoperative monitoring view is shown in In the case of patients with unclear intraoperative ABR wave V waveform by standard click sound stimulation, we tried to create and use another sound stimulation by which clearer wave V waveforms could be observed in each patient. Stimulation sounds were optimized by modifying the rise/fall time, plateau time, and frequency of the sound based on tone pips or tone burst sounds. Once the sound source that could induce a clearer wave V was obtained, the sound was used for continuous intraoperative monitoring . This modification of the stimulation sound was performed after general anesthesia and before starting tumor resection. The surgery was performed as previously reported . A U-shaThe value of the endoscope has been reported in previous studies of vestibular schwannoma surgery in which it was applied in combination with a retrolabyrinthine approach ,17,18. TThirty-three patients  were included in this study. The average age of the patients at the surgery was 47.3 ± 13.7 years old. The average size of the tumors was 17.4 ± 5.7 mm , IIa (N = 18), IIb (N = 2), III (N = 8), and IV (N = 1)). In 26 of the 33 cases (79%), preservation of hearing equivalent to that before surgery or improved hearing was achieved . In fiveNext, the postoperative hearing results were analyzed based on the classification suggested in our previous report of ABR wave V latency and OAE . In clasFinally, we analyzed the extent of tumor resection in each patient. Total tumor resection or near-total resection was achieved in 18 of 33 patients (55%) . Based oTo improve the postoperative hearing preservation rate in vestibular schwannoma surgery, we attempted to modify the retrolabyrinthine approach under reinforced continuous intraoperative monitoring for vestibular schwannoma by modifying our previous approach ,7. The mAccording to previous reports, the rate of hearing preservation using the retrolabyrinthine approach is approximately 22–50% ,19,20. BIt has been known that vestibular schwannoma could cause sudden or gradual hearing loss in its natural history ,22,23. SRadiation therapy is thought to be beneficial for patients with vestibular schwannoma with relatively good hearing levels because radiation therapy is thought to be associated with a low risk of hearing loss. Short-term observation of patients after radiation therapy showed a good hearing preservation rate; however, recent long-term follow-up studies showed gradual hearing loss after radiation therapy, and serviceable hearing levels were lost in most cases within ten years ,27,28,29While we observed an improvement in the hearing preservation rate, several points should be addressed in future studies. In particular, we allowed partial resection in some cases, whereas total tumor resection has been preferred for long-term tumor control in previous studies. It has been reported that total tumor resection or nearly total resection showed a better local control rate of vestibular schwannoma than subtotal or partial resection. Subtotal resection is reportedly followed by tumor regrowth within two years in as many as 27.6% of patients ,34, wherOur study revealed that a higher near-total resection rate was achieved under a surgical policy prioritizing hearing preservation in classes A and B. This result indicates that, if possible, surgery should be considered before ABR or OAE disturbance becomes obvious. In this study, we also revealed that in class C and D patients, tumor resection was limited to subtotal or partial resection in more patients. Whether this limitation of tumor resection could affect residual hearing levels after surgery, especially during long-term follow-up, should be carefully observed and examined in future studies.In this study, we showed that an 80% hearing preservation rate could be achieved using our modified surgical approach with the retrolabyrinthine approach under modified reinforced continuous intraoperative monitoring for hearing preservation. This result suggests that early intervention by surgery could be considered before ABR and OAE disturbance are evident. In addition, our results may broaden the application of hearing preservation surgery for vestibular schwannoma.


This article examines the relationship between twentieth- and twenty-first-century paleobiology. After summarizing the disciplinary problem of paleontology in the mid-twentieth century, I focus on five representative research topics in contemporary paleontology. In doing so, I outline twenty-first-century paleontology as a science that seeks more data, more technology, and more integration. At the end of the paper, I highlight a possible new paleobiological revolution: it would give paleontologists strong political representation to deal with issues such as expanded evolutionary synthesis, conservation of the Earth’s environment, and global climate change.In this paper, I will briefly discuss the elements of novelty and continuity between twentieth-century paleobiology and twenty-first-century paleontology. First, I will outline the heated debate over the disciplinary status of paleontology in the mid-twentieth century. Second, I will analyze the main theoretical issue behind this debate by considering two prominent case studies within the broader paleobiology agenda. Third, I will turn to twenty-first century paleontology and address five representative research topics. In doing so, I will characterize twenty-first century paleontology as a science that strives for more data, more technology, and more integration. Finally, I will outline what twenty-first-century paleontology might inherit from twentieth-century paleobiology: the pursuit of and plea for a new synthesis that could lead to a second paleobiological revolution. Following in the footsteps of the paleobiological revolution of the 1960s and 1970s, the paleobiological revolution of the twenty-first century would enable paleontologists to gain strong political representation and argue with a decisive voice at the “high table” on issues such as the expanded evolutionary synthesis, the conservation of Earth’s environment, and global climate change. Tempo and Mode in Evolution (1944), North American paleontologist George Gaylord Simpson (1902–1984) provided an interesting picture of the difficulties and lack of interaction between the paleontological and biological communities during the middle of the twentieth century. He wrote, “not long ago […] geneticists said that paleontology had no further contributions to make to biology, that […] it was a subject too purely descriptive to merit the name “science”. The paleontologist, they believed, is like a man who undertakes to study the principles of the internal combustion engine by standing on a street corner and watching the motor cars whiz by”  that time, the attitude of populations genetics to any paleontologist rash enough to offer a contribution to evolutionary theory has been to tell him go away and find another fossil, and not to bother the grownups” [0–2004 noIn welcoming paleontology to the table that matters, the geneticist paved the way for some historical and theoretical questions: What happened between the 1960s and 1980s that was so imprinted as to make his judgment change? Does twenty-first-century paleontology still sit at the high-table? And how does the scientific agenda of today’s paleontology relate to its scientific past and future?more data, more technology, and more integration. Moreover, I will I focus on the notion of the “second digital revolution” as it occurs in paleontology. In the conclusion, I will state what twenty-first-century paleontology might take from twentieth-century paleobiology: the aspiration of and plea for a new synthesis that may lead to a second paleobiological revolution.In this paper, I will briefly address these questions, in effect reflecting on the elements of novelty and continuity between twentieth-century paleobiology and twenty-first-century paleontology. First, I will expose the heated debate about the disciplinary status of paleontology during the mid-twentieth century. Second, I will analyze the main theoretical issue behind this debate by looking at two prominent case studies within the broader paleobiological agenda. Third, I will move to twenty-first-century paleontology and address five representative research topics. By doing so, I will characterize twenty-first-century paleontology as a science that seeks “We are paleontologists, so we need a name to contrast ourselves with all you folks who study modern organisms in human or ecological time. You therefore become neontologists” . With hiSecond, Gould contrasted between evolutionary investigations of living organisms  and the paleo(bio)ontological ones, which study what happened in the deep past. Indeed, Gould’s statement derived from the empirical results he himself and other paleontologists were obtaining during the 1960s and 1970s. These scientists were keen to present their discipline as a rigorous investigation of evolutionary mechanisms. By uncovering deep-time patterns and processes, paleontologists were indeed able to contribute to and expand the evolutionary mechanisms set during the modern synthesis of evolution. Gould coupled this theoretical aim with a broader idea of science, paleontology, and evolutionary time ,9,10,11.Paleobiology, arguing that “Nature’s discontinuities occur at different scales of time or tiers”. He distinguished three distinct temporal tiers. The first tier includes events at the ecological movement; the second tier encompasses events which occur during “millions of years in “normal” geological time”; whereas the most exciting subject in paleontology lies in our recognition that one of our best-recognized and most puzzling phenomena, mass extinction, is not merely more and quicker of the same, but a third distinct tier with rules and principles of its own [As noted, the second ground behind Gould’s provocative statement was his emphasis on the importance of deep-time investigations as defining characteristic of paleontology. Although the discovery and conquest of deep time was a classical argument for the importance of paleontology since the seventeenth century ,14,15,16 its own .Successively, he stated that “whatever accumulates at the first tier is sufficiently reversed, undone, or overridden by processes of the higher tiers” . For insGould’s idea was that evolutionary time could be seen as a system of distinct tiers—and the problem of transpacific evolution requires an explicit study of their interaction. Darwinian tradition leads us to deny this kind of structuring, to view time as a continuous, and to seek the source of causality at all scales in observable events and processes at smallest ,18.To put it simply, Gould and colleagues meant to “(1) make paleontology more theoretical and less descriptive; (2) introduce models and quantitative analysis into paleontological methodology; (3) import ideas and techniques from other disciplines  into paleontology; (4) emphasize the evolutionary implications of the fossil record” . Or, as Following these starting points, Gould asserted that paleontology was a legitimate biological discipline able to uncover patterns and mechanisms which could be found at the second and tier tiers of time . For insPaleobiology, Gould wrote to the journal’s editor, Jack Sepkoski, explaining the necessity of an interaction between different and autonomous layers of the evolutionary theory:Nine months after his article "The Paradox of the first Tier" was submitted to Hierarchy, as here discussed in its genealogical context, is an ‘internalistic’ theory about evolution dynamics. And we need to formulate it properly if we are to tackle this internal dynamic with the other great mover of life’s patterns—the externals of geological history especially mass extinctions, that so impact life’s history…in other words, all the data that you and your colleagues are treating in such new and exciting ways. Hierarchy confronts the geological dynamic, and we will not get it right until we reformulate both sides. Gould to Sepkoski, 13 August 1985 in [In this letter, Gould clearly affirmed the importance of reformulating the hierarchical model of evolution in the light of the momentous and exciting research techniques used in the investigation of mass extinctions. The reformulation Gould had in mind, however, concerned the entire paleontological discipline. He suggested a “nomothetic and idiographic” approach to the fossil record based upon David Raup and Sepkoski’s studies on the structure of the mass extinction ,23,24.The Kantian philosopher Wilhelm Windelband (1848–1915) coined the nomothetic vs. idiographic distinction. On May 4, 1894, he gave his rectoral address on the methodological differences between History and Natural Science at the Kaiser-Wilhelms-Universität Strasburg. During that address, he distinguished historical from natural sciences by focusing on the “formal character of their cognitive goals” . NomotheTo accomplish the reformulation, Gould promoted a methodological synthesis. He clearly suggested this in commenting on Sepkoski’s study on Phanerozoic diversity ,27. GoulCompendium. It gave the required data a mathematical treatment of data. This in turn made visible what is invisible: the structure and development of the Phanerozoic diversity [The ideographic factors mentioned by Gould derive from Sepkoski’s famous iversity ,29.Hence, the contrast between paleontology and paleobiology was mainly based on disciplinary and methodological issues. Gould and colleagues first created a disciplinary space in which to insert their research agenda . Successively, they sought to a possible methodological and disciplinary synthesis, in effect avoiding possible dichotomies. Famously and quoting German philosopher Immanuel Kant, Gould wrote “with all biology and no geology, paleontology is empty; but with geology alone, it is blind” . FurtherIt is quite difficult to find well-preserved fossils that immediately resemble living organisms that can also be exhibited, used, and taken at face value. In fact, once an organism dies, it is subjected to the several taphonomic processes. These processes destroy and change the features of the original organism. For instance, it is rare to find fossils with their soft parts preserved. There are two ways to practically address this problem: (1) focus on structures that are more frequently preserved; (2) focus on exceptionally well-preserved sites. These provide more selective observations that can be essential, but have their limitations when studying rapid changes during evolution The imperfect and incomplete nature of the paleontological record gave several paleontologists cause to reflect on the epistemic aspect of the fossil record. As a result, paleontologists came up with practices intended to overcome the incomplete nature of the records of the past. In addition to working with imperfect and incomplete data, paleontologists must face another difficulty: the so-called over and underdetermination issue.As philosopher of science Carol E. Cleland has pointed out, historical sciences, such as paleontology, are subjected to the asymmetry of overdetermination ,33. Theyinformation-destroying processes” [Following Turner, we can develop the thought experiment a bit further. “The owners of the house sweep up the shards, throw the baseball in the bin, and eventually repair the window. A few weeks later, the only traces of the event that remain are a few shards of glass under the refrigerator. The housecleaning and repair are examples of what Sober  calls ocesses” .Let us follow Turner again in this line of reasoning. Let us assume that a future investigator discovers glass shards on the kitchen floor. He will then ask what kind of shards they are—are they pieces of a glass, a window, a vase, etc.? “Even if the historical investigator recognizes the traces for what they are”, noted Turner, “rival hypotheses about earlier events and processes will often be underdetermined by the available traces. After studying the shards under the refrigerator, the historical investigator will be completely confused: The evidence does not permit her to discriminate at all between incompatible opposing hypotheses  In other words, she confronts a local underdetermination problem” .Therefore, the present event  over- or under-determines its possible causes. Replaying the tape of time, we cannot be sure to identify the correct sequence of cause–effect, since there are many possible causal chains backwards from the local event.Hence, first, the record of the past is always imperfect and incomplete, and second, we are not able to state whether our imperfect and incomplete data overdetermine or underdetermine the phenomena paleontologist would like to investigate.Given these two issues, how can paleontologists bring out patterns and mechanisms that might expand evolutionary theory? Are these two issues not a death kiss for paleontology? And more broadly, what is paleontological business about? To answer these questions, I will briefly recall some research results Gould himself put in the middle of his agenda.One main topic of twentieth-century paleobiology was the debate about the importance and dynamics of mass extinction ,35. One Due to Alvarez’s team discovery (1978) of the iridium anomaly in rocks formation at K–T boundary, mass extinction became the hot topic of paleontology in the 1980s. One of the main questions during those years was concerning the number and intensity of the mass extinctions.This issue was resolved in two famous papers written by David Raup and Jack Sepkoski. Using Sepkoski’s database (1982), Raup and Sepkoski identified the number of mass extinctions and the periodicity of this phenomenon. Sepkoski and Raup plotted a huge number of fossil marine families against geological time and found that five mass extinctions clearly occurred in the history of the Earth as “statistically distinct from the background extinction levels”. These “five extinction events are seen as sharp drops in standing diversity”, and therefore they were easily detected. A mass extinction is thus an event in which a “large number of organisms have disappeared over relatively short time” ,23.highly integrative practice used in twentieth-century paleobiology. As for the seminal investigation of morphogenesis conducted by David Raup and Adolf Seilacher during the 1960s and 1970s [the fruitful combination of science and technology. This implied that phenomena such as mass-extinctions or a life-like display of extinct specimens in a museum’s hall depend both on the correct use of technological devices and on the interplay between these devices and theories. Hence, paleobiology can be seen as a phenomena-lead discipline. These “investigations are such because the relevance of evidence turns on relationships between phenomena, the hypotheses pertaining to them” [This case study is emblematic since it shows the nd 1970s ,38, alsoto them”  and, I wto them” .What is left of the paleobiological research agenda? As I will detail in the conclusion, twentieth-century paleobiology shares with twenty-first-century paleontology the needs for integration and synthesis. In this section, I would like to briefly single out five promising research topics of current paleontology and connect them with twentieth-century paleobiology. I would like to characterize the research of twenty-first-century paleontology with a slogan: more data, more technology, and more integration.The first topic I chose is about the emergence of paleocolor as a testable field of enquiry. To achieve this aim, it is important to have more clean data. In addition to the publication of studies on feather taphonomy, scientists are teaming up to use ion beam scanning electron microscopy to investigate the preserved melanin pigments. By integrating more data with more technologies, paleocolor can provided precious insights into the behavior and ecology of extinct organisms ,46,47,48Second, as noted, one main issue paleontologists have to face is the lack of appropriate data. The clarification around the preservability of organic chemicals in fossils, and more broadly, the mechanisms behind taphonomy, is another key research program of twenty-first-century paleontology. Also in this case, the choice and use of appropriate technologies  is essential to obtain more data and thus pose new questions on phylogenetic hypotheses ,52,53,54Orobates pabsti. This is a four-legged vertebrate organism that went extinct about 300 million years ago. The study of the morphology of this well-preserved specimen is very important because it could offer valuable insights into the evolution of terrestrial vertebrates. Orobates are an early evolution of the lineage that led to amniotes. These made the vertebrate transition to land by becoming independent of open water during the early stages of development. Thus, studying and understanding how these species were able to transition from water to land is essential to better understand one of the major transitions in vertebrate evolution.Third, another promising topic of twenty-first-century paleontology is given by the intersection between morphology, evolutionary theory, and various technologies. The intersection between robotics and morphology provides one compelling example. Scientists are working together with engineers to model and construct bio-inspired robots to understand evolution. One example above all  is giveOrobates. The OroBot was built in collaboration with bioengineers at the École Polytechnique Fédérale de Lausanne (EPFL) in Lausanne. The spine of the OroBot was segmented into eight joints: two for the neck, four for the trunk, and two for the tail. The feet consisted of three passive and compliant joints. The designed parts of OroBOT were made of polyamide plastic material and created by selective laser sintering. Working in vivo with these robots, Nyakatura’s team was able to reach conclusions about the complex form-function that characterized the vertebrates’ transition to land [To perform this research, scientists designed the OroBOT robot. It was designed to account for the locomotion dynamics of  to land ,57,58,59The same logic is behind the creation of a chewing machine, an artificial mechanical chewing machine, used to study the micro-wear process and the possible correlation with diet and the rate of tooth wear. As the authors noted, “the aim was a simplified system that would allow changing various factors in mastication, for example different standardized feeds, to test whether expectations based on a simplistic interpretation of microscopic and macroscopic wear could be confirmed. The aim of this study was to produce microwear features seen in nature, i.e., pits and scratches, and to quantify macroscopic wear with real teeth and diets, in order to achieve a detailed picture of the wear process and its components” . As in tThis synergy between technology and paleontological research has also taken different forms in the present day. Among them, one is virtual paleontology ,65,66,67The fourth hot topic of twenty-first-century paleontology is deeply rooted in the twentieth-century paleobiology. As noted in the introduction, paleobiology was launched to reorient the paleontological agenda toward broader evolutionary problems. This was the main reason for the paleobiological revolution of the 1960s and 1970s—think of Eldredge and Gould’s call for punctuated equilibrium. The same search for new evolutionary mechanisms pervaded paleobiological research during the first encounters with the emerging evo-devo community. Or rather, the evolution of evo-devo was shaped by paleobiological questions from the beginning, and vice versa. In fact, at the 1981 Dahlem conference on “Evolution and Development”, which will be considered as the grounding meeting of evolutionary developmental biology as an autonomous evolutionary discipline, biologists and paleontologists discussed together the relationship between evolution and development. For instance, in the working group on “The Role of Development in Macroevolutionary Change” biologists, such as Jim Murray, Pere Alberch, Brian Goodwin, Gunther Wagner, Tony Hoffman, and David Wake, defined with paleontologists Stephen Gould, Adolf Seilacher, and David Raup the role of constrains in evolution ,68,69,70The same line of continuity and interaction denotes current paleontology, which even formalizes the paleontological contribution to evo-devo as Paleo-Evo-Devo. Therefore, the paleontology of the twenty-first century is also characterized by the search for a strong integration in this fourth case ,77,78,79The fifth topic I have singled out is also anchored in the twentieth-century paleobiological agenda: the discussion of abiotic and biotic factors in evolution. Recall that I opened this paper with a quote from Maynard Smith. He welcomed the return of paleontology to the high table as a result of Raup and Sepkoski’s findings on mass extinction and the consequent focus on biotic elements in evolution. This research, in turn, had emerged from the study of the dynamics of Phanerozoic marine paleodiversity  and the Red Queen model proposed by Leigh Van Valen .Twenty-first-century paleontology is capitalizing on this line of research. At the same time, paleontologists are trying to synthetize biotic and abiotic factors. For instance, Mike Benton notes, “The realization that the Red Queen and Court Jester models may be scale-dependent, and that evolution may be pluralistic, opens opportunities for dialog” . He goesAlong these lines, paleontologist Tyler Faith and his colleagues emphasized the key methodological elements of current hominin evolution. First, paleoanthropology, as paleontology, is all about data and time scales (or as Gould put it tiers): “There is no universally ‘correct’ scale of observation, but to address questions linking ecology and evolution, the scales of the processes of interest must align with the scales of the available data” . Second,cooperative effort to understand the (deep) past. As paleontological data are always imperfect and incomplete, paleontologists should omnivorously assimilate every method to successfully and opportunistically work on and with deep time [What do the five topics just discussed tell us about the elements of continuity between twentieth-century paleobiology and twenty-first-century paleontology? First, both enterprises called paleontologists’ attention to a eep time ,84,85. Meep time . Sometimeep time ). How, hIndeed, this implies a return to the sprit embodied by the paleobiological revolution of the mid twentieth-century. At the end, what Gould and colleagues were asking for was a genuine synthesis of knowledge. They asked for blurring the disciplinary borders between natural and historical sciences as well as between science and technology. This spirit should be put at the center of twenty-first-century paleontology – this agenda is also perused by other technoscientific disciplines such as biorobotics, synthetic biology, nano(bio)technology, etc. See, for instance, ,89,90,91Methods in Ecology and Evolution 2016, 7. Furthermore, it is perhaps worth noting that Wolfgang Kiessling was the first paleontologist to play a major role in the Intergovernmental Panel on Climate Change (IPCC) report on climate change, working on ”Climate Change 2021: Impacts, Adaptation and Vulnerability“, thus bridging the gap between the two communities - I thank one referee for this. See also [A future task for philosophers and historians of paleontology would be to understand the various practices and reasons for the paleontological plea for synthesis and integration in the last century. In other words, the analysis should focus on what (and why) paleontologists sought (and are seeking) collaboration with neontologists and promote the circulation of knowledge and technologies   on the production of paleontological knowledge. In addition to the flood of data and the transformation of the paleontologist into a data scientist (and vice versa), gy today ,99,100. gy today ,105,106.Hence, and to conclude, if constructively interpreted and read through the recent history of paleontology, the five topics singled out may provide some potentialities for a new synthesis between genetic and morphological approaches to the evolution of forms in the attempt to overcome the limits, issues, and problems of phylogenetic reconstructions. The major implication would be a broader reflection on what paleontology might become in light of recent technical and molecular revolutions. This would imply a second paleobiological revolution. In fact, as David Sepkoski put it, “the paleobiological “revolution” was more like a political contest in which one group perceives itself to be disenfranchised and agitates for greater representation in government than a contest of lofty ideas. The 1970s was a period of revolution in paleontology because paleobiologists saw themselves, and described what they were doing, as revolutionary” . Echoing