Skin Biopsy Detection of Phosphorylated α-Synuclein in Patients With Synucleinopathies.

Importance: Finding a reliable diagnostic biomarker for the disorders collectively known as synucleinopathies (Parkinson disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA], and pure autonomic failure [PAF]) is an urgent unmet need. Immunohistochemical detection of cutaneous phosphorylated α-synuclein may be a sensitive and specific clinical test for the diagnosis of synucleinopathies. Objective: To evaluate the positivity rate of cutaneous α-synuclein deposition in patients with PD, DLB, MSA, and PAF. Design, Setting, and Participants: This blinded, 30-site, cross-sectional study of academic and community-based neurology practices conducted from February 2021 through March 2023 included patients aged 40 to 99 years with a clinical diagnosis of PD, DLB, MSA, or PAF based on clinical consensus criteria and confirmed by an expert review panel and control participants aged 40 to 99 years with no history of examination findings or symptoms suggestive of a synucleinopathy or neurodegenerative disease. All participants completed detailed neurologic examinations and disease-specific questionnaires and underwent skin biopsy for detection of phosphorylated α-synuclein. An expert review panel blinded to pathologic data determined the final participant diagnosis. Exposure: Skin biopsy for detection of phosphorylated α-synuclein. Main Outcomes: Rates of detection of cutaneous α-synuclein in patients with PD, MSA, DLB, and PAF and controls without synucleinopathy. Results: Of 428 enrolled participants, 343 were included in the primary analysis (mean [SD] age, 69.5 [9.1] years; 175 [51.0%] male); 223 met the consensus criteria for a synucleinopathy and 120 met criteria as controls after expert panel review. The proportions of individuals with cutaneous phosphorylated α-synuclein detected by skin biopsy were 92.7% (89 of 96) with PD, 98.2% (54 of 55) with MSA, 96.0% (48 of 50) with DLB, and 100% (22 of 22) with PAF; 3.3% (4 of 120) of controls had cutaneous phosphorylated α-synuclein detected. Conclusions and Relevance: In this cross-sectional study, a high proportion of individuals meeting clinical consensus criteria for PD, DLB, MSA, and PAF had phosphorylated α-synuclein detected by skin biopsy. Further research is needed in unselected clinical populations to externally validate the findings and fully characterize the potential role of skin biopsy detection of phosphorylated α-synuclein in clinical care.

Matriliny reverses gender disparities in inflammation and hypertension among the Mosuo of China.

Women experience higher morbidity than men, despite living longer. This is often attributed to biological differences between the sexes; however, the majority of societies in which these disparities are observed exhibit gender norms that favor men. We tested the hypothesis that female-biased gender norms ameliorate gender disparities in health by comparing gender differences in inflammation and hypertension among the matrilineal and patrilineal Mosuo of China. Widely reported gender disparities in health were reversed among matrilineal Mosuo compared with patrilineal Mosuo, due to substantial improvements in women's health, with no concomitant detrimental effects on men. These findings offer evidence that gender norms limiting women's autonomy and biasing inheritance toward men adversely affect the health of women, increasing women's risk for chronic diseases with tremendous global health impact.

Intrapartum uterine activity and neonatal outcomes: a systematic review.

BACKGROUND: Increased uterine activity (UA) may not allow adequate recovery time for foetal oxygenation. METHODS: The aim of the study was to determine if increased UA during labour is associated with an increased risk of either short- or long-term neurological injury in term neonates, or with neonatal proxy measures of intrapartum hypoxia-ischemia. MEDLINE, CINAHL, and ClinicalTrials.gov were searched using the following terms: uterine activity, excessive uterine activity, XSUA, uterine hyperstimulation, and tachysystole. Any study that analysed the relationship between UA during term labour and neurological outcomes/selected proxy neurological outcomes was eligible for inclusion. Outcomes from individual studies were reported in tables and presented descriptively with odds ratios (OR) and 95% confidence intervals (CI) for dichotomous outcomes and means with standard deviations for continuous outcomes. Where group numbers were provided, ORs and their CIs were calculated according to Altman. MAIN RESULTS: Twelve studies met the inclusion criteria. Seven studies featured umbilical artery pH as an individual outcome. Umbilical artery base excess and Apgar scores were both reported as individual outcomes in four studies. No study examined long term neurodevelopmental outcomes and only one study reported on encephalopathy as an outcome. The evidence for a relationship between UA and adverse infant outcomes was inconsistent. The reported estimated effect size varied from non-existent to clinically significant. CONCLUSIONS: There is some evidence that increased UA may be a non-specific predictor of depressed neurological function in the newborn, but it is inconsistent and insufficient to support the conclusion that an association generally exists.

Role of the CD39/CD73 Purinergic Pathway in Modulating Arterial Thrombosis in Mice.

OBJECTIVE: Circulating blood cells and endothelial cells express ectonucleoside triphosphate diphosphohydrolase-1 (CD39) and ecto-5'-nucleotidase (CD73). CD39 hydrolyzes extracellular ATP or ADP to AMP. CD73 hydrolyzes AMP to adenosine. The goal of this study was to examine the interplay between CD39 and CD73 cascade in arterial thrombosis. APPROACH AND RESULTS: To determine how CD73 activity influences in vivo thrombosis, the time to ferric chloride-induced arterial thrombosis was measured in CD73-null mice. In response to 5% FeCl3, but not to 10% FeCl3, there was a significant decrease in the time to thrombosis in CD73-null mice compared with wild-type mice. In mice overexpressing CD39, ablation of CD73 did not inhibit the prolongation in the time to thrombosis conveyed by CD39 overexpression. However, the CD73 inhibitor α-ß-methylene-ADP nullified the prolongation in the time to thrombosis in human CD39 transgenic (hC39-Tg)/CD73-null mice. To determine whether hematopoietic-derived cells or endothelial cell CD39 activity regulates in vivo arterial thrombus, bone marrow transplant studies were conducted. FeCl3-induced arterial thrombosis in chimeric mice revealed a significant prolongation in the time to thrombosis in hCD39-Tg reconstituted wild-type mice, but not on wild-type reconstituted hCD39-Tg mice. Monocyte depletion with clodronate-loaded liposomes normalized the time to thrombosis in hCD39-Tg mice compared with hCD39-Tg mice treated with control liposomes, demonstrating that increased CD39 expression on monocytes protects against thrombosis. CONCLUSIONS: These data demonstrate that ablation of CD73 minimally effects in vivo thrombosis, but increased CD39 expression on hematopoietic-derived cells, especially monocytes, attenuates in vivo arterial thrombosis.

Sex-biased gene regulation varies across human populations as a result of adaptive evolution.

OBJECTIVES: Studies of human sexual dimorphism and gender disparities in health focus on ostensibly universal molecular sex differences, such as sex chromosomes and circulating hormone levels, while ignoring the extraordinary diversity in biology, behavior, and culture acquired by different human populations over their unique evolutionary histories. MATERIALS AND METHODS: Using RNA-Seq data and whole genome sequences from 1000G and HGDP, we investigate variation in sex-biased gene expression across 11 human populations and test whether population-level variation in sex-biased expression may have resulted from adaptive evolution in regions containing sex-specific regulatory variants. RESULTS: We find that sex-biased gene expression in humans is highly variable, mostly population-specific, and demonstrates between population reversals. Expression quantitative trait locus mapping reveals sex-specific regulatory regions with evidence of recent positive natural selection, suggesting that variation in sex-biased expression may have evolved as an adaptive response to ancestral environments experienced by human populations. DISCUSSION: These results indicate that sex-biased gene expression is more flexible than previously thought and is not generally shared among human populations. Instead, molecular phenotypes associated with sex depend on complex interactions between population-specific molecular evolution and physiological responses to contemporary socioecologies.

Dynamics of manual impaction instruments during total hip arthroplasty.

Aims: Manual impaction, with a mallet and introducer, remains the standard method of installing cementless acetabular cups during total hip arthroplasty (THA). This study aims to quantify the accuracy and precision of manual impaction strikes during the seating of an acetabular component. This understanding aims to help improve impaction surgical techniques and inform the development of future technologies. Methods: Posterior approach THAs were carried out on three cadavers by an expert orthopaedic surgeon. An instrumented mallet and introducer were used to insert cementless acetabular cups. The motion of the mallet, relative to the introducer, was analyzed for a total of 110 strikes split into low-, medium-, and high-effort strikes. Three parameters were extracted from these data: strike vector, strike offset, and mallet face alignment. Results: The force vector of the mallet strike, relative to the introducer axis, was misaligned by an average of 18.1°, resulting in an average wasted strike energy of 6.1%. Furthermore, the mean strike offset was 19.8 mm from the centre of the introducer axis and the mallet face, relative to the introducer strike face, was misaligned by a mean angle of 15.2° from the introducer strike face. Conclusion: The direction of the impact vector in manual impaction lacks both accuracy and precision. There is an opportunity to improve this through more advanced impaction instruments or surgical training.

The effects of the industrial transition on lower limb bone structure: A comparison of the inhabitants of Pecos Pueblo and present-day Indigenous peoples of New Mexico.

OBJECTIVES: Comparisons between Indigenous peoples over time and within a particular geographic region can shed light on the impact of environmental transitions on the skeleton, including relative bone strength, sexual dimorphism, and age-related changes. Here we compare long bone structural properties of the inhabitants of the late prehistoric-early historic Pecos Pueblo with those of present-day Indigenous individuals from New Mexico. MATERIALS AND METHODS: Femora and tibiae of 126 adults from Pecos Pueblo and 226 present-day adults were included in the study. Cross-sectional diaphyseal properties-areas and second moments of area-were obtained from past studies of the Pecos Pueblo skeletal sample, and from computed tomography scans of recently deceased individuals in the present-day sample. RESULTS: Femora and tibiae from Pecos individuals are stronger relative to body size than those of present-day Indigenous individuals. Present-day individuals are taller but not wider, and this body shape difference affects cross-sectional shape, more strongly proximally. The tibia shows anteroposterior strengthening among Pecos individuals, especially among males. Sexual dimorphism in midshaft bone shape is stronger within the Pecos Pueblo sample. With aging, Pecos individuals show more medullary expansion but also more subperiosteal expansion than present-day individuals, maintaining bone strength despite cortical thinning. DISCUSSION: Higher activity levels, carried out over rough terrain and throughout adult life, likely explain the relatively stronger lower limb bones of the Pecos individuals, as well as their greater subperiosteal expansion with aging. Greater sexual dimorphism in bone structure among Pecos individuals potentially reflects greater gender-based differences in behavioral patterns.

Predicting choice behaviour in economic games using gaze data encoded as scanpath images.

Eye movement data has been extensively utilized by researchers interested in studying decision-making within the strategic setting of economic games. In this paper, we demonstrate that both deep learning and support vector machine classification methods are able to accurately identify participants' decision strategies before they commit to action while playing games. Our approach focuses on creating scanpath images that best capture the dynamics of a participant's gaze behaviour in a way that is meaningful for predictions to the machine learning models. Our results demonstrate a higher classification accuracy by 18% points compared to a baseline logistic regression model, which is traditionally used to analyse gaze data recorded during economic games. In a broader context, we aim to illustrate the potential for eye-tracking data to create information asymmetries in strategic environments in favour of those who collect and process the data. These information asymmetries could become especially relevant as eye-tracking is expected to become more widespread in user applications, with the seemingly imminent mass adoption of virtual reality systems and the development of devices with the ability to record eye movement outside of a laboratory setting.

Inheritance and inequality among nomads of South Siberia.

At the headwaters of the Yenisei River in Tuva and northern Mongolia, nomadic pastoralists move between camps in a seasonal rotation that facilitates their animals' access to high-quality grasses and shelter. The use and informal ownership of these camps depending on season helps illustrate evolutionary and ecological principles underlying variation in property relations. Given relatively stable patterns of precipitation and returns to capital improvement, families generally benefit from reusing the same camps year after year. We show that locations with higher economic defensibility and capital investment-winter camps and camps located in mountain/river valleys-are claimed and inherited more frequently than summer camps and camps located in open steppe. Camps are inherited patrilineally and matrilineally at a ratio of 2 : 1. Despite its practical importance, camp inheritance is not associated with livestock wealth today, which is better predicted by education and wealth outside the pastoral economy. The relationship between the livestock wealth of parents and their adult children is significantly positive, but relatively low compared to other pastoralists. The degree of inequality in livestock wealth, however, is very close to that of other pastoralists. This is understandable considering the durability and defensibility of animal wealth and economies of scale common across pastoralists. This article is part of the theme issue 'Evolutionary ecology of inequality'.

Effects of the energy balance transition on bone mass and strength.

Chronic positive energy balance has surged among societies worldwide due to increasing dietary energy intake and decreasing physical activity, a phenomenon called the energy balance transition. Here, we investigate the effects of this transition on bone mass and strength. We focus on the Indigenous peoples of New Mexico in the United States, a rare case of a group for which data can be compared between individuals living before and after the start of the transition. We show that since the transition began, bone strength in the leg has markedly decreased, even though bone mass has apparently increased. Decreased bone strength, coupled with a high prevalence of obesity, has resulted in many people today having weaker bones that must sustain excessively heavy loads, potentially heightening their risk of a bone fracture. These findings may provide insight into more widespread upward trends in bone fragility and fracture risk among societies undergoing the energy balance transition.

Fetal heart rate patterns in labor and the risk of neonatal encephalopathy: A case control study.

OBJECTIVE: To describe the accuracy of intrapartum fetal heart rate abnormalities as defined by National Institute of Health and Care Excellence guidelines to predict moderate-severe neonatal encephalopathy of apparent hypoxic-ischemic etiology. STUDY DESIGN: A case-control study of HIE risk factors was conducted. Eligible babies were born in a single maternity hospital in Dublin, Ireland between September 2006, and November 2017 at ≥35 + 0 weeks' gestational age. Cases were eligible babies with moderate-severe neonatal encephalopathy of definite or apparent hypoxic-ischemic etiology. Controls were eligible babies born before and after each case with normal Apgar scores. The included subjects who had intrapartum fetal heart rate recordings were identified. Pattern features (baseline rate, variability, accelerations, decelerations [early, late, variable, prolonged], bradycardia, sinusoidal pattern) were manually identified blind to all clinical details by one of the authors. Each 15-minute segment was then algorithmically categorized (uninterpretable, normal, suspicious, pathological). RESULTS: Of 88 cases and 176 controls, 71 cases (81%) and 146 controls (83%) were admitted to the delivery suite in labor. From that group, intrapartum FHR traces longer than 15 min were available for 52 (73%) cases and 118 (83%) controls. The FHR pattern feature with the largest area under the receiver operating characteristic curve was the maximum number of consecutive segments in which the baseline was >160 bpm (0.71 [95% confidence interval: 0.62-0.80]). The category variable with the highest area under the curve was the number of suspicious segments (0.76 [95% confidence interval: 0.67-0.84]). A tri-variate logistic regression model incorporating the total number of segments, the number of "suspicious" segments classed, and the number of "pathological" segments achieved an area under the curve of 0.78 (95% confidence interval: 0.70-0.86). With 95% specificity, this model correctly identified 17 cases (33%) at a median time before delivery of 2 h and 18 min (interquartile range: 01:19-04:40). CONCLUSIONS: The power of fetal heart rate analysis to predict neonatal encephalopathy is hampered by poor specificity given the rarity of the outcome. When analyzing a suspicious trace, it is beneficial to consider the overall duration of the suspicious pattern.

Uterine activity in labour and the risk of neonatal encephalopathy: a case control study.

OBJECTIVE: To determine the relationship between intrapartum contraction frequency, rest interval duration, and cervical dilation speed and the risk of neonatal hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: This was a retrospective case-control study conducted in a maternity hospital in Dublin, Ireland. Babies born without major congenital anomalies between September 2006 and November 2017 at ≥ 35 + 0 weeks' gestational age were eligible. Cases were diagnosed with moderate-severe HIE. The controls were the first eligible baby born before and after each case with normal Apgar scores and not admitted to the neonatal unit. Intrapartum uterine activity was assessed by automated analysis of external tocography recordings. Cervical dilation was assessed by linear interpolation between vaginal examination measurements. The speed of cervical dilation was expressed as the times from 4 to 6 cm, >6 cm to the start of pushing, and from pushing to delivery. RESULTS: Intrapartum tocographs results were available in 49 of 88 cases and 121 of 176 controls. The median contraction rate in cases was 7.7 (Interquartile range [IQR]: 6.6-9.0) compared to 7.0 in controls (IQR: 6.2-7.9) (p = 0.021). The median rest interval duration was 56 s (IQR: 38-76) in cases and 62 s (IQR: 50-79) in controls (p = 0.058). Cases took longer to progress from > 6 cm to the start of pushing (cases: 02:58 [01:14-04:49], controls: 01:48 [00:51-03:34], p = 0.020) and from pushing to delivery (cases: 00:34 [00:24-01:10], controls: 00:27 [00:13-00:56], p = 0.036). CONCLUSIONS: Higher contraction frequencies and slower progress towards the end of labour are both independently associated with the risk of moderate-severe HIE. Inter-contraction rest interval duration as measured by external tocography does not provide additional accuracy.

Landscape of mutations in early stage primary cutaneous melanoma: An InterMEL study.

It is unclear why some melanomas aggressively metastasize while others remain indolent. Available studies employing multi-omic profiling of melanomas are based on large primary or metastatic tumors. We examine the genomic landscape of early-stage melanomas diagnosed prior to the modern era of immunological treatments. Untreated cases with Stage II/III cutaneous melanoma were identified from institutions throughout the United States, Australia and Spain. FFPE tumor sections were profiled for mutation, methylation and microRNAs. Preliminary results from mutation profiling and clinical pathologic correlates show the distribution of four driver mutation sub-types: 31% BRAF; 18% NRAS; 21% NF1; 26% Triple Wild Type. BRAF mutant tumors had younger age at diagnosis, more associated nevi, more tumor infiltrating lymphocytes, and fewer thick tumors although at generally more advanced stage. NF1 mutant tumors were frequent on the head/neck in older patients with severe solar elastosis, thicker tumors but in earlier stages. Triple Wild Type tumors were predominantly male, frequently on the leg, with more perineural invasion. Mutations in TERT, TP53, CDKN2A and ARID2 were observed often, with TP53 mutations occurring particularly frequently in the NF1 sub-type. The InterMEL study will provide the most extensive multi-omic profiling of early-stage melanoma to date. Initial results demonstrate a nuanced understanding of the mutational and clinicopathological landscape of these early-stage tumors.

A wavelet-based algorithm for automated analysis of external tocography: How does it compare to human interpretation?

BACKGROUND: Studies which use external tocography to explore the relationship between increased intrapartum uterine activity and foetal outcomes are feasible because the technology is safe and ubiquitous. However, periods of poor signal quality are common. We developed an algorithm which aims to calculate tocograph summary variables based on well-recorded contractions only, ignoring artefact and excluding sections deemed uninterpretable. The aim of this study was to test that algorithm's reliability. METHODS: Whole recordings from labours at ≥35 weeks of gestation were randomly selected without regard to quality. Contractions and rest intervals were measured by two humans independently, and by the algorithm using two sets of models; one based on a series of pre-defined thresholds, and another trained to imitate one of the human interpreters. The absolute agreement intraclass correlation coefficient (ICC) was calculated using a two-way random effects model. RESULTS: The training dataset included data from 106 tocographs. Of the tested algorithms, AdaBoost showed the highest initial cross-validated accuracy and proceeded to optimization. Forty tocographs were included in the validation set. The ICCs for the per tocograph mean contraction rates were; human B to human A: 0.940 (0.890-0.968), human A to initial models: 0.944 (0.898-0.970), human A to trained models 0.962 (0.927-0.980), human B to initial models: 0.930 (0.872-0.962), human B to trained models: 0.948 (0.903-0.972). CONCLUSIONS: The algorithm described approximates interpretation of external tocography performed by trained humans. The performance of the AdaBoost trained models was marginally superior compared to the initial models.

Hearing impairment and hypoxia ischaemic encephalopathy: Incidence and associated factors.

OBJECTIVE: To establish the local incidence of hearing loss in newborns with Hypoxic Ischaemic Encephalopathy (HIE) and to identify associated risk factors. STUDY DESIGN: Retrospective Cohort Study. Neonatal Intensive Care Unit (NICU) dual stage hearing screening protocol, including automated otoacoustic emissions (AOAE) and automated auditory brainstem response (AABR) testing. RESULTS: 57 newborns received therapeutic hypothermia for HIE. Twelve babies (21%) died. Audiology data was incomplete in 3 babies. Complete data was available for 42 babies (male n = 24), 4 (9.5%) of whom had hearing impairment. The development of hearing loss was associated with abnormal blood glucose levels (p = 0.006), low Apgar score at 1 min (p = 0.0219) and evidence of multi organ dysfunction [high creatinine (p = 0.0172 and 0.0198) and raised liver transaminases (aspartate aminotransferase (AST) p = 0.0012, alanine aminotransferase (ALT) p = 0.0037)]. An association with gentamicin was not found. CONCLUSION: This study confirms that hearing impairment is common in term infants who have undergone therapeutic hypothermia for moderate/severe HIE. Blood glucose should be monitored carefully in these infants and developmental surveillance should include formal audiology. Further larger studies are needed to clarify the role, if any, of hypothermia per se in causation of hearing loss and to fully identify risk factors for hearing impairment in this population. WHAT IS NEW: The current study confirms that hearing impairment is common in term infants who have undergone therapeutic hypothermia for moderate/severe HIE. No association between gentamicin use and the development of hearing impairment was found however initial blood glucose outside the normal range was of significance. Other factors associated with hearing impairment were low Apgar scores, greater need for resuscitation and evidence of multi organ dysfunction (renal and liver failure).

Timing of administration of antenatal magnesium sulfate and umbilical cord blood magnesium levels in preterm babies.

BACKGROUND: The optimum timing of administration of magnesium sulfate (MgSO4) in relation to delivery is not known. The general consensus is to achieve administration to the mother at least 4 hours prior to preterm delivery. OBJECTIVE: To investigate potential predictors of umbilical cord blood magnesium (Mg) concentrations, in particular, timing of antenatal MgSO4 administration in relation to delivery. STUDY DESIGN: A prospective observational study of infants delivered at less than 32 weeks' gestational age. Cord bloods samples were collected at delivery and Mg levels analyzed. RESULTS: Of the 81 included cases, five received no antenatal MgSO4, 65 received a 4 g bolus only, and 11 received a 4 g bolus and 1 g/hour infusion. The median time of bolus administration before delivery was 104 minutes (IQR: 57-215). The mean magnesium level was 0.934 mmol/L in the no antenatal MgSO4 group, 1.018 mmol/L in the bolus only group, and 1.225 mmol/L in the bolus and infusion group (p < .05). In the bolus only group, the highest mean magnesium concentration (1.091 mmol/L) was achieved with administration 1-2 hours before delivery, but the difference was small and not statistically significant. On multiple regression analysis, lower birthweight Z scores and gestational age were independently associated with higher cord blood Mg levels. CONCLUSIONS: In the bolus only group, the highest mean Mg levels were observed with administration 1-2 hours before delivery, but the findings were not statistically significant. Compared to the rest of the cohort, higher Mg levels were found when a bolus was followed by an infusion. Following a MgSO4 bolus, some growth restricted extremely preterm babies may have higher Mg levels than would be otherwise expected.

Kinship ties across the lifespan in human communities.

A hypothesis for the evolution of long post-reproductive lifespans in the human lineage involves asymmetries in relatedness between young immigrant females and the older females in their new groups. In these circumstances, inter-generational reproductive conflicts between younger and older females are predicted to resolve in favour of the younger females, who realize fewer inclusive fitness benefits from ceding reproduction to others. This conceptual model anticipates that immigrants to a community initially have few kin ties to others in the group, gradually showing greater relatedness to group members as they have descendants who remain with them in the group. We examine this prediction in a cross-cultural sample of communities, which vary in their sex-biased dispersal patterns and other aspects of social organization. Drawing on genealogical and demographic data, the analysis provides general but not comprehensive support for the prediction that average relatedness of immigrants to other group members increases as they age. In rare cases, natal members of the community also exhibit age-related increases in relatedness. We also find large variation in the proportion of female group members who are immigrants, beyond simple traditional considerations of patrilocality or matrilocality, which raises questions about the circumstances under which this hypothesis of female competition are met. We consider possible explanations for these heterogenous results, and we address methodological considerations that merit increased attention for research on kinship and reproductive conflict in human societies. This article is part of the theme issue 'The evolution of female-biased kinship in humans and other mammals'.

Evolutionary demography of age at last birth: integrating approaches from human behavioural ecology and cultural evolution.

Cultural evolutionary theory and human behavioural ecology offer different, but compatible approaches to understanding human demographic behaviour. For much of their 30 history, these approaches have been deployed in parallel, with few explicit attempts to integrate them empirically. In this paper, we test hypotheses drawn from both approaches to explore how reproductive behaviour responds to cultural changes among Mosuo agriculturalists of China. Specifically, we focus on how age at last birth (ALB) varies in association with temporal shifts in fertility policies, spatial variation and kinship ecologies. We interpret temporal declines in ALB as plausibly consistent with demographic front-loading of reproduction in light of fertility constraints and later ages at last birth in matrilineal populations relative to patrilineal ones as consistent with greater household cooperation for reproductive purposes in the former. We find little evidence suggesting specific transmission pathways for the spread of norms regulating ALB, but emphasize that the rapid pace of change strongly suggests that learning processes were involved in the general decline in ALB over time. The different predictions of models we employ belie their considerable overlap and the potential for a synthetic approach to generate more refined tests of evolutionary hypotheses of demographic behaviour.This article is part of the theme issue 'Bridging cultural gaps: interdisciplinary studies in human cultural evolution'.

Neutral lipid storage disease with myopathy: Further phenotypic characterization of a rare PNPLA2 variant.

Neutral lipid storage disease with myopathy is a rare disorder of lipid metabolism caused by variants in the Patatin-Like Phospholipase Domain Containing 2 (PNPLA2) gene. Diagnosis is often delayed due to variable presentations, which is of concern due to increased risk of cardiomyopathy. Better phenotype-genotype characterization is necessary to improve speed and accuracy of diagnosis. Here, we describe a 32-year-old woman of Hmong descent with progressive muscle pain and weakness who had a muscle biopsy with characteristic features of a lipid storage myopathy. Genetic testing revealed a homozygous splice site variant in PNPLA2, c.757 + 1G > T. This case, in combination with the one previously reported case of this PNPLA2 variant, also in a family of Hmong descent, suggests this particular variant may be unique to the Hmong population, a Southeast Asian minority group living in the United States, who immigrated to the United States as refugees after the Vietnam War.