Genomic landscapes of divergence among island bird populations: Evidence of parallel adaptation but at different loci?

When populations colonise new environments, they may be exposed to novel selection pressures but also suffer from extensive genetic drift due to founder effects, small population sizes and limited interpopulation gene flow. Genomic approaches enable us to study how these factors drive divergence, and disentangle neutral effects from differentiation at specific loci due to selection. Here, we investigate patterns of genetic diversity and divergence using whole-genome resequencing (>22× coverage) in Berthelot's pipit (Anthus berthelotii), a passerine endemic to the islands of three north Atlantic archipelagos. Strong environmental gradients, including in pathogen pressure, across populations in the species range, make it an excellent system in which to explore traits important in adaptation and/or incipient speciation. First, we quantify how genomic divergence accumulates across the speciation continuum, that is, among Berthelot's pipit populations, between sub species across archipelagos, and between Berthelot's pipit and its mainland ancestor, the tawny pipit (Anthus campestris). Across these colonisation timeframes (2.1 million-ca. 8000 years ago), we identify highly differentiated loci within genomic islands of divergence and conclude that the observed distributions align with expectations for non-neutral divergence. Characteristic signatures of selection are identified in loci associated with craniofacial/bone and eye development, metabolism and immune response between population comparisons. Interestingly, we find limited evidence for repeated divergence of the same loci across the colonisation range but do identify different loci putatively associated with the same biological traits in different populations, likely due to parallel adaptation. Incipient speciation across these island populations, in which founder effects and selective pressures are strong, may therefore be repeatedly associated with morphology, metabolism and immune defence.

Forty years of struggle in North Carolina: Workplace segregation and fatal occupational injury rates.

OBJECTIVE: To assess workplace segregation in fatal occupational injury from 1992 to 2017 in North Carolina. METHODS: We calculated occupational fatal injury rates within categories of occupation, industry, race, age, and sex; and estimated expected numbers of fatalities among Black and Hispanic male workers had they experienced the rates of White male workers. We also estimated the contribution of workforce segregation to disparities by estimating the expected number of fatalities among Black and Hispanic male workers had they experienced the industry and occupation patterns of White male workers. We assessed person-years of life-lost, using North Carolina life expectancy estimates. RESULTS: Hispanic workers contributed 32% of their worker-years and experienced 58% of their fatalities in construction. Black workers were most overrepresented in the food manufacturing industry. Hispanic males experienced 2.11 (95% CI: 1.86-2.40) times the mortality rate of White males. The Black-White and Hispanic-White disparities were widest among workers aged 45 and older, and segregation into more dangerous industries and occupations played a substantial role in driving disparities. Hispanic workers who suffered occupational fatalities lost a median 47 life-years, compared to 37 among Black workers and 36 among White workers. CONCLUSIONS: If Hispanic and Black workers experienced the workplace safety of their White counterparts, fatal injury rates would be substantially reduced. Workforce segregation reflects structural racism, which also contributes to mortality disparities. Root causes must be addressed to eliminate disparities.

Double-Clad Antiresonant Hollow-Core Fiber and Its Comparison with Other Fibers for Multiphoton Micro-Endoscopy.

Label-free and multiphoton micro-endoscopy can transform clinical histopathology by providing an in situ tool for diagnostic imaging and surgical treatment in diseases such as cancer. Key to a multiphoton imaging-based micro-endoscopic device is the optical fiber, for distortion-free and efficient delivery of ultra-short laser pulses to the sample and effective signal collection. In this work, we study a new hollow-core (air-filled) double-clad anti-resonant fiber (DC-ARF) as a high-performance candidate for multiphoton micro-endoscopy. We compare the fiber characteristics of the DC-ARF with a single-clad anti-resonant fiber (SC-ARF) and a solid core fiber (SCF). In this work, while the DC-ARF and the SC-ARF enable low-loss (<0.2 dBm-1), close to dispersion-free excitation pulse delivery (<10% pulse width increase at 900 nm per 1 m fiber) without any induced non-linearities, the SCF resulted in spectral broadening and pulse-stretching (>2000% of pulse width increase at 900 nm per 1 m fiber). An ideal optical fiber endoscope needs to be several meters long and should enable both excitation and collection through the fiber. Therefore, we performed multiphoton imaging on endoscopy-compatible 1 m and 3 m lengths of fiber in the back-scattered geometry, wherein the signals were collected either directly (non-descanned detection) or through the fiber (descanned detection). Second harmonic images were collected from barium titanate crystals as well as from biological samples (mouse tail tendon). In non-descanned detection conditions, the ARFs outperformed the SCF by up to 10 times in terms of signal-to-noise ratio of images. Significantly, only the DC-ARF, due to its high numerical aperture (NA) of 0.45 and wide-collection bandwidth (>1 µm), could provide images in the de-scanned detection configuration desirable for endoscopy. Thus, our systematic characterization and comparison of different optical fibers under different image collection configurations, confirms and establishes the utility of DC-ARFs for high-performing label-free multiphoton imaging-based micro-endoscopy.

Heat-related fatalities in North Carolina 1999-2017.

OBJECTIVES: Research shows the highest rates of occupational heat-related fatalities among farm laborers and among Black and Hispanic workers in North Carolina (NC). The Hispanic population and workforce in NC have grown substantially in the past 20 years. We describe the epidemiology of heat-related fatal injuries in the general population and among workers in NC. METHODS: We reviewed North Carolina death records and records of the North Carolina Office of the Chief Medical Examiner to identify heat-related deaths (primary International Classification of Diseases, Tenth Revision diagnosis code: X30 or T67.0-T67.9) that occurred between January 1, 1999, and December 31, 2017. Decedent age, sex, race, and ethnicity were extracted from both the death certificate and the medical examiner's report as well as determinations of whether the death occurred at work. RESULTS: In NC between 1999 and 2017, there were 225 deaths from heat-related injuries, and 25 occurred at work. The rates of occupational heat-related deaths were highest among males, workers of Hispanic ethnicity, workers of Black, multiple, or unknown race, and in workers aged 55-64. The highest rate of occupational heat-related deaths occurred in the agricultural industry. CONCLUSIONS: Since the last report (2001), the number of heat-related fatalities has increased, but fewer were identified as workplace fatalities. Rates of occupational heat-related deaths are highest among Hispanic workers. NC residents identifying as Black are disproportionately burdened by heat-related fatalities in general, with a wider apparent disparity in occupational deaths.

Life history correlations and trade-offs resulting from selection for dispersal in Tribolium castaneum.

Dispersal is an important facet of the life history of many organisms and is therefore subject to selective pressure, but does not evolve in isolation. Across nature there are examples of dispersal syndromes, life history strategies in which suites of traits coevolve and covary with dispersal in combinations that serve to maximise fitness in a given ecological context. The red rust flour beetle, Tribolium castaneum, is a model organism and globally significant post-harvest pest which relies on dispersal to reach new patches of ephemeral habitat. Dispersal behaviour in Tribolium has a strong genetic basis. However, a robust understanding of the relationship between dispersal and other life history components, which could elucidate evolutionary processes and allow pest managers to control their spread and reduce the impact of infestation, is currently lacking. Here we use highly replicated lines of T. castaneum previously artificially selected for divergent small-scale dispersal propensity, to robustly test several important life history components: reproductive strategy, development time and longevity. As predicted, we find that a suite of important change as result of our selection on dispersal; high dispersal propensity is associated with a lower number of longer mating attempts by males, lower investment in early-life reproduction by females, slower development of later-laid offspring and longer female lifespan. These findings indicate that correlated intraspecific variation in dispersal and related traits may represent alternative life history strategies in T. castaneum. We therefore suggest that pest management efforts to mitigate the species' agro-economic impact should consider the eco-evolutionary dynamics within multiple life-histories. The benefits of doing so could be felt both through improved targetting of efforts to reduce spread, and also in forecasting of how the selection pressures applied through pest management are likely to affect pest evolution.

Single proxy control.

Negative control variables are sometimes used in nonexperimental studies to detect the presence of confounding by hidden factors. A negative control outcome (NCO) is an outcome that is influenced by unobserved confounders of the exposure effects on the outcome in view, but is not causally impacted by the exposure. Tchetgen Tchetgen (2013) introduced the Control Outcome Calibration Approach (COCA) as a formal NCO counterfactual method to detect and correct for residual confounding bias. For identification, COCA treats the NCO as an error-prone proxy of the treatment-free counterfactual outcome of interest, and involves regressing the NCO on the treatment-free counterfactual, together with a rank-preserving structural model, which assumes a constant individual-level causal effect. In this work, we establish nonparametric COCA identification for the average causal effect for the treated, without requiring rank-preservation, therefore accommodating unrestricted effect heterogeneity across units. This nonparametric identification result has important practical implications, as it provides single-proxy confounding control, in contrast to recently proposed proximal causal inference, which relies for identification on a pair of confounding proxies. For COCA estimation we propose 3 separate strategies: (i) an extended propensity score approach, (ii) an outcome bridge function approach, and (iii) a doubly-robust approach. Finally, we illustrate the proposed methods in an application evaluating the causal impact of a Zika virus outbreak on birth rate in Brazil.

Potential sources of time lags in calibrating species distribution models.

The Anthropocene is characterized by a rapid pace of environmental change and is causing a multitude of biotic responses, including those that affect the spatial distribution of species. Lagged responses are frequent and species distributions and assemblages are consequently pushed into a disequilibrium state. How the characteristics of environmental change-for example, gradual 'press' disturbances such as rising temperatures due to climate change versus infrequent 'pulse' disturbances such as extreme events-affect the magnitude of responses and the relaxation times of biota has been insufficiently explored. It is also not well understood how widely used approaches to assess or project the responses of species to changing environmental conditions can deal with time lags. It, therefore, remains unclear to what extent time lags in species distributions are accounted for in biodiversity assessments, scenarios and models; this has ramifications for policymaking and conservation science alike. This perspective piece reflects on lagged species responses to environmental change and discusses the potential consequences for species distribution models (SDMs), the tools of choice in biodiversity modelling. We suggest ways to better account for time lags in calibrating these models and to reduce their leverage effects in projections for improved biodiversity science and policy.

COVID-19 vaccine reactogenicity among participants enrolled in the GENCOV study.

BACKGROUND: GENCOV is a prospective, observational cohort study of COVID-19-positive adults. Here, we characterize and compare side effects between COVID-19 vaccines and determine whether reactogenicity is exacerbated by prior SARS-CoV-2 infection. METHODS: Participants were recruited across Ontario, Canada. Participant-reported demographic and COVID-19 vaccination data were collected using a questionnaire. Multivariable logistic regression was performed to assess whether vaccine manufacturer, type, and previous SARS-CoV-2 infection are associated with reactogenicity. RESULTS: Responses were obtained from n = 554 participants. Tiredness and localized side effects were the most common reactions across vaccine doses. For most participants, side effects occurred and subsided within 1-2 days. Recipients of Moderna mRNA and AstraZeneca vector vaccines reported reactions more frequently compared to recipients of a Pfizer-BioNTech mRNA vaccine. Previous SARS-CoV-2 infection was independently associated with developing side effects. CONCLUSIONS: We provide evidence of relatively mild and short-lived reactions reported by participants who have received approved COVID-19 vaccines.

Genotype-environment associations reveal genes potentially linked to avian malaria infection in populations of an endemic island bird.

Patterns of pathogen prevalence are, at least partially, the result of coevolutionary host-pathogen interactions. Thus, exploring the distribution of host genetic variation in relation to infection by a pathogen within and across populations can provide important insights into mechanisms of host defence and adaptation. Here, we use a landscape genomics approach (Bayenv) in conjunction with genome-wide data (ddRADseq) to test for associations between avian malaria (Plasmodium) prevalence and host genetic variation across 13 populations of the island endemic Berthelot's pipit (Anthus berthelotii). Considerable and consistent spatial heterogeneity in malaria prevalence was observed among populations over a period of 15 years. The prevalence of malaria infection was also strongly positively correlated with pox (Avipoxvirus) prevalence. Multiple host loci showed significant associations with malaria prevalence after controlling for genome-wide neutral genetic structure. These sites were located near to or within genes linked to metabolism, stress response, transcriptional regulation, complement activity and the inflammatory response, many previously implicated in vertebrate responses to malarial infection. Our findings identify diverse genes - not just limited to the immune system - that may be involved in host protection against malaria and suggest that spatially variable pathogen pressure may be an important evolutionary driver of genetic divergence among wild animal populations, such as Berthelot's pipit. Furthermore, our data indicate that spatio-temporal variation in multiple different pathogens (e.g. malaria and pox in this case) may have to be studied together to develop a more holistic understanding of host pathogen-mediated evolution.

Measuring waning protection from seasonal influenza vaccination during nine influenza seasons, Ontario, Canada, 2010/11 to 2018/19.

BackgroundWaning immunity from seasonal influenza vaccination can cause suboptimal protection during peak influenza activity. However, vaccine effectiveness studies assessing waning immunity using vaccinated and unvaccinated individuals are subject to biases.AimWe examined the association between time since vaccination and laboratory-confirmed influenza to assess the change in influenza vaccine protection over time.MethodsUsing linked laboratory and health administrative databases in Ontario, Canada, we identified community-dwelling individuals aged ≥ 6 months who received an influenza vaccine before being tested for influenza by RT-PCR during the 2010/11 to 2018/19 influenza seasons. We estimated the adjusted odds ratio (aOR) for laboratory-confirmed influenza by time since vaccination (categorised into intervals) and for every 28 days.ResultsThere were 53,065 individuals who were vaccinated before testing for influenza, with 10,264 (19%) influenza-positive cases. The odds of influenza increased from 1.05 (95% CI: 0.91-1.22) at 42-69 days after vaccination and peaked at 1.27 (95% CI: 1.04-1.55) at 126-153 days when compared with the reference interval (14-41 days). This corresponded to 1.09-times increased odds of influenza every 28 days (aOR = 1.09; 95% CI: 1.04-1.15). Individuals aged 18-64 years showed the greatest decline in protection against influenza A(H1N1) (aORper 28 days = 1.26; 95% CI: 0.97-1.64), whereas for individuals aged ≥ 65 years, it was against influenza A(H3N2) (aORper 28 days = 1.20; 95% CI: 1.08-1.33). We did not observe evidence of waning vaccine protection for individuals aged < 18 years.ConclusionsInfluenza vaccine protection wanes during an influenza season. Understanding the optimal timing of vaccination could ensure robust protection during seasonal influenza activity.

Considerations for developing and implementing a safe list for alien taxa.

Many species have been intentionally introduced to new regions for their benefits. Some of these alien species cause damage, others do not (or at least have not yet). There are several approaches to address this problem: prohibit taxa that will cause damage, try to limit damages while preserving benefits, or promote taxa that are safe. In the present article, we unpack the safe list approach, which we define as "a list of taxa alien to the region of interest that are considered of sufficiently low risk of invasion and impact that the taxa can be widely used without concerns of negative impacts." We discuss the potential use of safe lists in the management of biological invasions; disentangle aspects related to the purpose, development, implementation, and impact of safe lists; and provide guidance for those considering to develop and implement such lists.

Reduced Proactive and Reactive Cognitive Flexibility in Older Adults Underlies Performance Costs During Dual-Task Walking: A Mobile Brain/Body Imaging (MoBI) Study.

Age-related reductions in cognitive flexibility may limit modulation of control processes during systematic increases to cognitive-motor demands, exacerbating dual-task costs. In this study, behavioral and neurophysiologic changes to proactive and reactive control during progressive cognitive-motor demands were compared across older and younger adults to explore the basis for age-differences in cognitive-motor interference (CMI). 19 younger (19 - 29 years old, mean age = 22.84 +/- 2.75 years, 6 male, 13 female) and 18 older (60 - 77 years old, mean age = 67.89 +/- 4.60 years, 9 male, 9 female) healthy adults completed cued task-switching while alternating between sitting and walking on a treadmill. Gait kinematics, task performance measures, and brain activity were recorded using electroencephalography (EEG) based Mobile Brain/Body Imaging (MoBI). Response accuracy on easier trial types improved in younger, but not older adults when they walked while performing the cognitive task. As difficulty increased, walking provoked accuracy costs in older, but not younger adults. Both groups registered faster responses and reduced gait variability during dual-task walking. Older adults exhibited lower amplitude modulations of proactive and reactive neural activity as cognitive-motor demands systematically increased, which may reflect reduced flexibility for progressive preparatory and reactive adjustments over behavioral control.

Twenty-five year occupational homicide mortality trends in North Carolina: 1992-2017.

INTRODUCTION: Determining industry of decedents and victim-perpetrator relationships is crucial to inform and evaluate occupational homicide prevention strategies. In this study, we examine occupational homicide rates in North Carolina (NC) by victim characteristics, industry and victim-perpetrator relationship from 1992 to 2017. METHODS: Occupational homicides were identified from records of the NC Office of the Chief Medical Examiner system and the NC death certificates. Sex, age, race, ethnicity, class of worker, manner of death, victim-perpetrator relationship and industry were abstracted. Crude and age-standardised homicide rates were calculated as the number of homicides that occurred at work divided by an estimate of worker-years (w-y). Rate ratios and 95% CIs were calculated, and trends over calendar time in occupational homicide rates were examined overall and by industry. RESULTS: 456 homicides over 111 573 049 w-y were observed. Occupational homicide rates decreased from 0.82 per 100 000 w-y for the period 1992-1995 to 0.21 per 100 000 w-y for the period 2011-2015, but increased to 0.32 per 100 000 w-y in the period 2016-2017. Fifty-five per cent (252) of homicides were perpetrated by strangers. Taxi drivers experienced an occupational homicide rate that was 110 times (95% CI 76.52 to 160.19) the overall occupational homicide rate in NC; however, this rate declined by 76.5% between 1992 and 2017. Disparities were observed among workers 65+ years old, racially and ethnically minoritised workers and self-employed workers. CONCLUSION: Our findings identify industries and worker demographics that experienced high occupational homicide fatality rates. Targeted and tailored mitigation strategies among vulnerable industries and workers are recommended.

Higher-order evidence.

Higher-order evidence is evidence about evidence. Epidemiologic examples of higher-order evidence include the settings where the study data constitute first-order evidence and estimates of misclassification comprise the second-order evidence (e.g., sensitivity, specificity) of a binary exposure or outcome collected in the main study. While sampling variability in higher-order evidence is typically acknowledged, higher-order evidence is often assumed to be free of measurement error (e.g., gold standard measures). Here we provide two examples, each with multiple scenarios where second-order evidence is imperfectly measured, and this measurement error can either amplify or attenuate standard corrections to first-order evidence. We propose a way to account for such imperfections that requires third-order evidence. Further illustrations and exploration of how higher-order evidence impacts results of epidemiologic studies is warranted.

A Feasibility Randomized Controlled Trial of Prehabilitation During Neoadjuvant Chemotherapy for Women with Breast Cancer: A Mixed Methods Study.

BACKGROUND: Limited data exist regarding the role of multimodal prehabilitation during neoadjuvant chemotherapy (NACT) for breast cancer. Determining large trial feasibility and identifying signals of prehabilitation benefit are needed. PATIENTS AND METHODS: We conducted a randomized controlled feasibility trial of multimodal prehabilitation versus usual care during NACT among women diagnosed with non-metastatic breast cancer. Intervention participants received an individualized exercise program, dietetic support, and stress management counseling during NACT. The trial assessed feasibility via rates of recruitment, attrition, adherence, and study-related adverse events. Physical fitness (Six Minute Walk Test, grip strength, anthropometrics) and patient-reported outcomes were assessed at baseline, after NACT completion, and 6 months after surgery as exploratory outcomes, and analyzed using linear mixed effects models. Qualitative data were collected from a subsample to understand feasibility and acceptability of prehabilitation. RESULTS: A total of 72 participants were enrolled from the 123 eligible patients (recruitment rate of 53%). There was a 13% attrition rate and no intervention-related adverse events. Participants in the prehabilitation group had better 6-min walk distance at the post-chemotherapy timepoint [between group difference of 49.43 m, 95% confidence interval (CI) - 118.1, 19.2] and at the post-surgery timepoint (27.3, 95% CI -96.8, 42.2) compared with the control group. Prehabilitation participants reported better quality of life, less fatigue, and improved physical activity levels compared with usual care participants. Interviews revealed that the intervention had a positive impact on the treatment experience. CONCLUSIONS: This study demonstrated feasibility and improvement in physical and psychosocial outcomes. Larger trials assessing intervention efficacy to confirm indications of prehabilitation benefit are warranted.

25-Year fatal workplace suicide trends in North Carolina: 1992-2017.

BACKGROUND: Suicide is a serious public health problem in the United States, but limited evidence is available investigating fatal suicides at work. There is a substantial need to characterize workplace suicides to inform suicide prevention interventions and target high-risk settings. This study aims to examine workplace suicide rates in North Carolina (NC) by worker characteristics, means of suicide used, and industry between 1992 and 2017. METHODS: Fatal workplace suicides were identified from records of the NC Office of the Chief Medical Examiner system and the NC death certificate. Sex, age, race, ethnicity, class of worker, manner of death, and industry were abstracted. Crude and age-standardized homicide rates were calculated as the number of suicides that occurred at work divided by an estimate of worker-years (w-y). Rate ratios and 95% confidence intervals (CIs) were calculated, and trends over calendar time for fatal workplace suicides were examined overall and by industry. RESULTS: 81 suicides over 109,464,430 w-y were observed. Increased rates were observed in workers who were male, self-employed, and 65+ years old. Firearms were the most common means of death (63%) followed by hanging (16%). Gas service station workers experienced the highest fatal occupational suicide rate, 11.5 times (95% CI: 3.62-36.33) the overall fatal workplace suicide rate, followed by Justice, Public Order, and Safety workers at 3.23 times the overall rate (95% CI: 1.31-7.97). CONCLUSION: Our findings identify industries and worker demographics that were vulnerable to workplace suicides. Targeted and tailored mitigation strategies for vulnerable industries and workers are recommended.

Part II: Blood Transfusion and Donor Exposure in the Surgical Management of Trigonocephaly Patients: A Protocol From Alder Hey Craniofacial Unit.

Trigonocephaly is a craniofacial malformation caused by premature fusion of the metopic suture. Surgical correction frequently results in the need for blood transfusion. Transfusion complications include transfusion-transmitted infections (TTIs), immune-mediated reactions, and volume overload. Donor exposure (DE) describes the number of blood products from unique donors with increasing DE equating to an increased risk of TTI. We evaluate data on 204 trigonocephaly patients covering 20 years of practice with respect to blood transfusions and DE. This represents the largest series from a single unit to date. A protocol based on our experiences has been devised that summarizes the key interventions we recommend to minimize blood transfusions and DE in craniofacial surgery. Patients operated on between 2000 and 2020 were included. DE and a range of values were calculated including estimated red cell loss (ERCL) and estimated red cell volume transfused (ERCVT). Groups were established by relevant interventions and compared using the Mann-Whitney U test. Mean DE fell from 1.46 at baseline to 0.85 ( P <0.05). Median allogenic transfusion volume fell from 350 mL at baseline to 250 mL ( P <0.05). Median ERCL fell from 15.05 mL/kg at baseline to 12.39 mL/kg and median ERCVT fell from 20.85 to 15.98 mL/kg. Changes in ERCL and ERCVT did not reach statistical significance. DE can be minimized with the introduction of key interventions such as a restrictive transfusion policy, preoperative iron, cell saver, tranexamic acid, and use of a matchstick burr for osteotomies.

The impact of helping experience on helper life-history and fitness in a cooperatively breeding bird.

Cooperative breeding occurs when helpers provide alloparental care to the offspring of a breeding pair. One hypothesis of why helping occurs is that helpers gain valuable skills that may increase their own future reproductive success. However, research typically focuses on the effect of helping on short-term measures of reproductive success. Fewer studies have considered how helping affects long-term fitness measures. Here, we analyze how helping experience affects key breeding and fitness-related parameters in the Seychelles warbler (Acrocephalus sechellensis). Importantly, we control for females that have cobred (reproduced as a subordinate by laying an egg within a territory in which they are not a dominant breeder), as they already have experience with direct reproduction. Helping experience had no significant association with any of the metrics considered, except that helpers had an older age at first dominance. Accounting for helping experience, females that had cobred produced more adult offspring (≥1 year) after acquiring dominance and had a higher lifetime reproductive success (LRS) than females that had never cobred. Our results suggest that, in the Seychelles warbler, helping experience alone does not increase the fitness of helpers in any of the metrics considered, and highlights the importance of separating the effects of helping from cobreeding. Our findings also emphasize the importance of analyzing the effect of helping at various life-history stages, as higher short-term fitness may not translate to an overall increase in LRS.

Raine's syndrome: rare disease from neurosurgical perspective.

Raine's syndrome (RS) is a rare genetic disorder. Only 25 cases are in literature. Occurs due to genetic mutation resulting in deranged bone metabolism. Few cases are reported discussing the neurosurgical ramifications of the disease. We report a child diagnosed with RS. He was presented with multisutural synostosis requiring craniofacial intervention with two vault expansions. Additionally, required VP shunt due to hydrocephalus. We consider our case unique among reports of RS, as our patient has survived for 10. He died due to valve obstruction of the VP shunt. We also present a review of relevant medical literature.