OpenHands: An Open-Source Statistical Shape Model of the Finger Bones.

This paper presents statistical shape models of the four fingers of the hand, with an emphasis on anatomic analysis of the proximal and distal interphalangeal joints. A multi-body statistical shape modelling pipeline was implemented on an exemplar training dataset of computed tomography (CT) scans of 10 right hands (5F:5M, 27-37 years, free from disease or injury) imaged at 0.3 mm resolution, segmented, meshed and aligned. Model generated included pose neutralisation to remove joint angle variation during imaging. Repositioning was successful; no joint flexion variation was observed in the resulting model. The first principal component (PC) of morphological variation represented phalanx size in all fingers. Subsequent PCs showed variation in position along the palmar-dorsal axis, and bone breadth: length ratio. Finally, the models were interrogated to provide gross measures of bone lengths and joint spaces. These models have been published for open use to support wider community efforts in hand biomechanical analysis, providing bony anatomy descriptions whilst preserving the security of the underlying imaging data and privacy of the participants. The model describes a small, homogeneous population, and assumptions cannot be made about how it represents individuals outside the training dataset. However, it supplements anthropometric datasets with additional shape information, and may be useful for investigating factors such as joint morphology and design of hand-interfacing devices and products. The model has been shared as an open-source repository ( https://github.com/abel-research/OpenHands ), and we encourage the community to use and contribute to it.

Effect of milk flow-rate switch-point settings on milking duration and udder health throughout lactation.

The objective of this study was to quantify the effects of different milk flow-rate switch-point settings on milking duration, somatic cell count (SCC), strip milk, teat condition, and milk yield in a grass-based system in a long-term experiment. Much work has already been conducted providing strong support for significant reduction in milking duration without effects on yield through increasing the flow-rate switch-point at which vacuum to the milking cluster ceases and the cluster is removed from the cow by means of a retracting cord. However, in practice many farms have not adopted this labor-saving technology on the basis that it may increase milk SCC. Recent research on commercial Irish dairy herds identified the contagious mastitis-causing pathogen Staphylococcus. aureus as the most prevalent pathogen detected. Staph. aureus could have a cyclical shedding pattern which would inhibit detection at certain time points. Therefore, to reliably assess the effect of milk flow-rate switch-points on SCC, a long-term study was required, consisting of multiple observations on cow-level SCC. The present study filled this gap in knowledge by informing on any effect that ceasing milking at different flow rates may have on milking duration and SCC levels, particularly with regard to spring calving grass-based systems. Four treatments, consisting of milk flow-rate switch-points increasing from 0.2 kg/min to 0.8 kg/min in steps of 0.2 kg/min, were deployed for 31 wk to cows at the Teagasc Research Centre at Moorepark, Ireland. The effect of treatment on daily milking duration was significant. The milking duration for a milk flow-rate switch-point of 0.8 kg/min was 95 s (14%) shorter than for 0.2 kg/min. We did not find a significant effect of increasing the milk flow-rate switch-point from 0.2 to 0.8 kg/min on milk yield or SCC in this long-term study. We did find a significant effect of week of experiment on milk SCC, whereby the SCC of the cows on the experiment increased similarly among treatment groups as lactation progressed. A significant reduction in dead time (time from cluster attachment to reach a milk flow rate of 0.2 kg/min) was also noted as the milk flow-rate switch-point increased. On average, reductions in dead time contributed 12% to the overall reductions in milking duration. Similarly, reductions in low flow time (time from a flow rate of 0.2 kg/min to cluster detachment at the end of milking) contributed 26% to the overall reductions in milking duration. Reductions in dead time and low flow time played a greater role in reducing p.m. milking duration rather than a.m. milking duration due to the milking interval practiced on the research farm.

Effect of milk flow rate switch-point settings on cow comfort and milking duration.

Automatic cluster removers (ACR) operate by ceasing vacuum to the cluster and detaching the milking unit from the udder by means of a retracting cord once the milk flow has decreased to a predefined level (i.e., the milk flow rate switch-point). There is a large body of literature on this topic indicating that increasing the flow rate switch-point (e.g., from 0.2 kg/min to 0.8 kg/min at the udder level) is effective in reducing milking duration while having little effect on milk yield or milk somatic cell count (SCC). However, despite these findings many farms still use a switch-point of 0.2 kg/min because it is believed that emptying the udder completely at each milking is a prerequisite for good dairy cow management, especially in relation to maintaining a low milk SCC. However, there may be additional undocumented benefits in terms of cow comfort to increasing the milk flow rate switch-point, because the low milk flow period at the end of milking is a high-risk time for inducing teat-barrel congestion. The objective of this study was to quantify the effect of 4 milk flow rate switch-point settings on cow comfort, milking duration, and milk yield. In this study, we applied 4 treatments consisting of different milk flow rate switch-points to cows in a crossover design in a spring calving grass based dairy herd in Ireland. The treatments were (1) MFR0.2, where the cluster was removed at a milk flow rate of 0.2 kg/min; (2) MFR0.4, where the cluster was removed at 0.4 kg/min; (3) MFR0.6, where the cluster was removed at 0.6 kg/min, and (4) MFR0.8, where the cluster was removed at 0.8 kg/min. Milking parameters were recorded by the parlor software and leg movements (i.e., kicks or steps) during milking were recorded with an accelerometer. These data were used as a proxy for cow comfort during milking. The results of this study showed significant differences in cow comfort across treatments, as indicated by cow stepping during milking, for a.m. milkings, but these differences were not detected for p.m. milkings, possibly because a.m. milkings were longer than p.m. milkings due to a 16:8 h milking interval on the research farm. Differences tended to distinguish the 2 lower-flow switch-point settings with greater leg movement against the 2 higher-flow switch-point settings with less leg movement during milking. The effect of treatment (milk flow rate switch-point) on daily milking duration was significant. The milk duration for MFR0.8 was 89 s (14%) shorter than MFR0.2. There was no significant effect of treatment on SCC in this study.

Effect of mechanical premilking stimulation on milking duration in late lactation.

This study documents the effect of mechanical prestimulation on the milking duration of pasture-based cows in late lactation to better harness increased capacity of automation in the milk harvesting process. Premilking stimulation, provided via manual or mechanical means, has been shown to promote the milk letdown reflex and assist in achieving quick, comfortable, and complete milk removal from the udder. The literature is lacking knowledge on the effect of mechanical premilking stimulation on milking duration, especially in late lactation and in pasture-based systems, and many pasture-based farms do not practice a full premilking routine because of a lack of labor availability. The current study addresses this gap in knowledge. In this study, we tested 2 treatments: (1) the No Stim treatment used normal farm milking settings with no premilking preparation and (2) the Stim treatment used 60 s of mechanical premilking stimulation, with a rate of 120 cycles per minute and a pulsator ratio of 30:70 on cluster attachment. Once the 60 s of stimulation had elapsed, normal milking settings resumed for the remainder of the milking. Sixty cows were enrolled in the study, which ran for 20 d. The effect of treatment on a.m. milking duration was significant, a.m. milking duration for Stim was 12 s shorter than that of No Stim. The effect of treatment on p.m. milk duration was not significant. Treatment had no effect on a.m./p.m. milk yields, average milk flowrates or peak milk flowrates. Significant differences emerged between treatments on a.m. and p.m. dead time (time from cluster attachment to reach a milk flowrate of 0.2 kg/min). The a.m. and p.m. dead times were 6 s shorter for Stim compared with No Stim. The time taken to achieve peak milk flowrate (time to peak) at morning milking was 7 s shorter for Stim compared with No Stim, and treatment yielded no significant effects on time to peak at p.m. milkings. Treatment also had no significant effect on log10 somatic cell count. Although the percentage of congested teat-ends and teat-barrels was numerically lower for Stim versus No Stim, no statistical differences were detected across these measures. Based on the results of the study, we found merit in applying 60 s of mechanical pre-stimulation at a.m. milking from a milking duration perspective. However, the strategy was not as successful for the p.m. milking. Analysis of the milk flowrate profiles recorded during the study suggest potential utility in employing different machine settings for various milkings based on anticipated yield and level of udder fill.

Insensitivity to Suffering: Psychopathic Traits and Perception of Others' Pain.

Despite growing evidence that psychopathy entails reduced emotional processing, the relationship between psychopathic traits and third-person pain perception is poorly understood. This study directly examined perception of others' pain in a sample of male and female students (N = 105) who completed the Self-Report Psychopathy scale (SRP-III) and the Toronto Empathy Questionnaire (TEQ). Participants watched a video of 60 one-second clips of other people experiencing pain. Following each clip, participants rated the perceived level of pain intensity and pain unpleasantness. Psychopathic traits were unrelated to response bias, suggesting that individuals high in psychopathic traits were no more or less likely to impute pain to others. However, higher levels of psychopathic traits, particularly callous affect and antisocial behavior, were associated with a decreased ability to discriminate others' pain. Sensitivity and response bias were unrelated to TEQ scores. These findings provide novel insights into the influence of psychopathic traits on emotional processing.

A randomised placebo-controlled trial of the effectiveness of early metformin in addition to usual care in the reduction of gestational diabetes mellitus effects (EMERGE): study protocol.

BACKGROUND: Pregnancies affected by gestational diabetes mellitus (GDM) are associated with an increased risk of adverse maternal and foetal outcomes. Current treatments for GDM involve initial medical nutritional therapy (MNT) and exercise and pharmacotherapy in those with persistent hyperglycaemia. Insulin is considered first-line pharmacotherapy but is associated with hypoglycaemia, excessive gestational weight gain (GWG) and an increased caesarean delivery rate. Metformin is safe in selected groups of women with GDM but is not first-line therapy in many guidelines due to a lack of long-term data on efficacy. The EMERGE trial will evaluate the effectiveness of early initiation of metformin in GDM. METHODS: EMERGE is a phase III, superiority, parallel, 1:1 randomised, double-blind, placebo-controlled trial comparing the effectiveness of metformin versus placebo initiated by 28 weeks (+6 days) plus usual care. Women aged 18-50 years will be recruited. Women with established diabetes, multiple pregnancies, known major congenital malformation or small for gestational age (<10th centile), intolerance or contraindication to the use of metformin, shock or sepsis, current gestational hypertension or pre-eclampsia, significant gastrointestinal problems, congestive heart failure, severe mental illness or galactose intolerance are excluded. INTERVENTION: Immediate introduction of metformin or placebo in addition to MNT and usual care. Metformin is initiated at 500mg/day and titrated to a maximum dose of 2500mg over 10 days. Women are followed up at 4 and 12 weeks post-partum to assess maternal and neonatal outcomes. The composite primary outcome measure is initiation of insulin or fasting blood glucose ≥ 5.1 mmol/L at gestational weeks 32 or 38. The secondary outcomes are the time to insulin initiation and insulin dose required; maternal morbidity at delivery; mode and time of delivery; postpartum glucose status; insulin resistance; postpartum body mass index (BMI); gestational weight gain; infant birth weight; neonatal height and head circumference at delivery; neonatal morbidities (neonatal care unit admission, respiratory distress, jaundice, congenital anomalies, Apgar score); neonatal hypoglycaemia; cost-effectiveness; treatment acceptability and quality of life determined by the EQ5D-5L scale. DISCUSSION: The EMERGE trial will determine the effectiveness and safety of early and routine use of metformin in GDM. TRIAL REGISTRATION: EudraCT Number 2016-001644-19l; NCT NCT02980276 . Registered on 6 June 2017.

Routine testing of close contacts of confirmed COVID-19 cases - National COVID-19 Contact Management Programme, Ireland, May to August 2020.

OBJECTIVES: The objective of this study was to inform public health practitioners who are designing, adapting and implementing testing and tracing strategies for Coronavirus disease (COVID-19) control. STUDY DESIGN: The study design is monitoring and evaluation of a national public health protection programme. METHODS: All close contacts of laboratory-confirmed cases of COVID-19 identified between the 19th May and 2nd August were included; secondary attack rates and numbers needed to test were estimated. RESULTS: Four thousand five hundred eighty six of 7272 (63%) close contacts of cases were tested with at least one test. The secondary attack rate in close contacts who were tested was 7% (95% Confidence Interval [CI]: 6.3 - 7.8%). At the 'day 0' test, 14.6% (95% CI: 11.6-17.6%) of symptomatic close contacts tested positive compared with 5.2% (95% CI: 4.4-5.9%) of asymptomatic close contacts. CONCLUSIONS: The application of additional symptom-based criteria for testing in this high-incidence population (close contacts) is of limited utility because of the low negative predictive value of absence of symptoms.

Automated vs. manual pain coding and heart rate estimations based on videos of older adults with and without dementia.

INTRODUCTION: Technological advances have allowed for the estimation of physiological indicators from video data. FaceReader™ is an automated facial analysis software that has been used widely in studies of facial expressions of emotion and was recently updated to allow for the estimation of heart rate (HR) using remote photoplethysmography (rPPG). We investigated FaceReader™-based heart rate and pain expression estimations in older adults in relation to manual coding by experts. METHODS: Using a video dataset of older adult patients with and without dementia, we assessed the relationship between FaceReader's™ HR estimations against a well-established Video Magnification (VM) algorithm during baseline and pain conditions. Furthermore, we examined the correspondence between the Facial Action Coding System (FACS)-based pain scores obtained through FaceReader™ and manual coding. RESULTS: FaceReader's™ HR estimations were correlated with VM algorithm in baseline and pain conditions. Non-verbal FaceReader™ pain scores and manual coding were also highly correlated despite discrepancies between the FaceReader™ and manual coding in the absolute value of scores based on pain-related facial action coding of the events preceding and following the pain response. CONCLUSIONS: Compared to expert manual FACS coding and optimized VM algorithm, FaceReader™ showed good results in estimating HR values and non-verbal pain scores.

Predictive prosthetic socket design: part 1-population-based evaluation of transtibial prosthetic sockets by FEA-driven surrogate modelling.

It has been proposed that finite element analysis can complement clinical decision making for the appropriate design and manufacture of prosthetic sockets for amputees. However, clinical translation has not been achieved, in part due to lengthy solver times and the complexity involved in model development. In this study, a parametric model was created, informed by variation in (i) population-driven residuum shape morphology, (ii) soft tissue compliance and (iii) prosthetic socket design. A Kriging surrogate model was fitted to the response of the analyses across the design space enabling prediction for new residual limb morphologies and socket designs. It was predicted that morphological variability and prosthetic socket design had a substantial effect on socket-limb interfacial pressure and shear conditions as well as sub-dermal soft tissue strains. These relationships were investigated with a higher resolution of anatomical, surgical and design variability than previously reported, with a reduction in computational expense of six orders of magnitude. This enabled real-time predictions (1.6 ms) with error vs the analytical solutions of < 4 kPa in pressure at residuum tip, and < 3% in soft tissue strain. As such, this framework represents a substantial step towards implementation of finite element analysis in the prosthetics clinic.

Predictive prosthetic socket design: part 2-generating person-specific candidate designs using multi-objective genetic algorithms.

In post-amputation rehabilitation, a common goal is to return to ambulation using a prosthetic limb, suspended by a customised socket. Prosthetic socket design aims to optimise load transfer between the residual limb and mechanical limb, by customisation to the user. This is a time-consuming process, and with the increase in people requiring these prosthetics, it is vital that these personalised devices can be produced rapidly while maintaining excellent fit, to maximise function and comfort. Prosthetic sockets are designed by capturing the residual limb's shape and applying a series of geometrical modifications, called rectifications. Expert knowledge is required to achieve a comfortable fit in this iterative process. A variety of rectifications can be made, grouped into established strategies [e.g. in transtibial sockets: patellar tendon bearing (PTB) and total surface bearing (TSB)], creating a complex design space. To date, adoption of advanced engineering solutions to support fitting has been limited. One method is numerical optimisation, which allows the designer a number of likely candidate solutions to start the design process. Numerical optimisation is commonly used in many industries but not prevalent in the design of prosthetic sockets. This paper therefore presents candidate shape optimisation methods which might benefit the prosthetist and the limb user, by blending the state of the art from prosthetic mechanical design, surrogate modelling and evolutionary computation. The result of the analysis is a series of prosthetic socket designs that preferentially load and unload the pressure tolerant and intolerant regions of the residual limb. This spectrum is bounded by the general forms of the PTB and TSB designs, with a series of variations in between that represent a compromise between these accepted approaches. This results in a difference in pressure of up to 31 kPa over the fibula head and 14 kPa over the residuum tip. The presented methods would allow a trained prosthetist to rapidly assess these likely candidates and then to make final detailed modifications and fine-tuning. Importantly, insights gained about the design should be seen as a compliment, not a replacement, for the prosthetist's skill and experience. We propose instead that this method might reduce the time spent on the early stages of socket design and allow prosthetists to focus on the most skilled and creative tasks of fine-tuning the design, in face-to-face consultation with their client.

Pain Expressions in Dementia: Validity of Observers' Pain Judgments as a Function of Angle of Observation.

Facial expressions of pain are important in assessing individuals with dementia and severe communicative limitations. Though frontal views of the face are assumed to allow for the most valid and reliable observational assessments, the impact of viewing angle is unknown. We video-recorded older adults with and without dementia using cameras capturing different observational angles (e.g., front vs. profile view) both during a physiotherapy examination designed to identify painful areas and during a baseline period. Facial responses were coded using the fine-grained Facial Action Coding System, as well as a systematic clinical observation method. Coding was conducted separately for panoramic (incorporating left, right, and front views), and a profile view of the face. Untrained observers also judged the videos in a laboratory setting. Trained coder reliability was satisfactory for both the profile and panoramic view. Untrained observer judgments from a profile view were substantially more accurate compared to the front view and accounted for more variance in differentiating non-painful from painful situations. The findings add specificity to the communications models of pain (clarifying factors influencing observers' ability to decode pain messages). Perhaps more importantly, the findings have implications for the development of computer vision algorithms and vision technologies designed to monitor and interpret facial expressions in a pain context. That is, the performance of such automated systems is heavily influenced by how reliably these human annotations could be provided and, hence, evaluation of human observers' reliability, from multiple angles of observation, has implications for machine learning development efforts.

Pain in severe dementia: A comparison of a fine-grained assessment approach to an observational checklist designed for clinical settings.

BACKGROUND: Fine-grained observational approaches to pain assessment (e.g. the Facial Action Coding System; FACS) are used to evaluate pain in individuals with and without dementia. These approaches are difficult to utilize in clinical settings as they require specialized training and equipment. Easy-to-use observational approaches (e.g. the Pain Assessment Checklist for Limited Ability to Communicate-II; PACSLAC-II) have been developed for clinical settings. Our goal was to compare a FACS-based fine-grained system to the PACSLAC-II in differentiating painful from non-painful states in older adults with and without dementia. METHOD: We video-recorded older long-term care residents with dementia and older adult outpatients without dementia, during a quiet baseline condition and while they took part in a physiotherapy examination designed to identify painful areas. Videos were coded using pain-related behaviours from the FACS and the PACSLAC-II. RESULTS: Both tools differentiated between painful and non-painful states, but the PACSLAC-II accounted for more variance than the FACS-based approach. Participants with dementia scored higher on the PACSLAC-II than participants without dementia. CONCLUSION: The results suggest that easy-to-use observational approaches for clinical settings are valid and that there may not be any clinically important advantages to using more resource-intensive coding approaches based on FACS. We acknowledge, as a limitation of our study, that we used as baseline a quiet condition that did not involve significant patient movement. In contrast, our pain condition involved systematic patient movement. Future research should be aimed at replicating our results using a baseline condition that involves non-painful movements. SIGNIFICANCE: Examining older adults with and without dementia, a brief observational clinical approach was found to be valid and accounted for more variance in differentiating pain-related and non-pain-related states than did a detailed time-consuming fine-grained approach.

Dopaminergic and behavioural changes in a loss-of-imprinting model of Cdkn1c.

The imprinted gene Cdkn1c is expressed exclusively from the maternally inherited allele as a consequences of epigenetic regulation. Cdkn1c exemplifies many of the functional characteristics of imprinted genes, playing a role in foetal growth and placental development. However, Cdkn1c also plays an important role in the brain, being key to the appropriate proliferation and differentiation of midbrain dopaminergic neurons. Using a transgenic model (Cdkn1cBACx1 ) with a twofold elevation in Cdkn1c expression that mimics loss-of-imprinting, we show that increased expression of Cdkn1c in the brain gives rise to neurobiological and behavioural changes indicative of a functionally altered dopaminergic system. Cdkn1cBACX1 mice displayed altered expression of dopamine system-related genes, increased tyrosine hydroxylase (Th) staining and increased tissue content of dopamine in the striatum. In addition, Cdkn1cBACx1 animals were hypersensitive to amphetamine as showed by c-fos expression in the nucleus accumbens. Cdkn1cBACX1 mice had significant changes in behaviours that are dependent on the mesolimbic dopaminergic system. Specifically, increased motivation for palatable food stuffs, as indexed on a progressive ratio task. In addition, Cdkn1cBACX1 mice displayed enhanced social dominance. These data show, for the first time, the consequence of elevated Cdkn1c expression on dopamine-related behaviours highlighting the importance of correct dosage of this imprinted gene in the brain. This work has significant relevance for deepening our understanding of the epigenetic factors that can shape neurobiology and behaviour.

Cobalt hydroxide nanoflakes and their application as supercapacitors and oxygen evolution catalysts.

Finding alternative routes to access and store energy has become a major issue recently. Transition metal oxides have shown promising behaviour as catalysts and supercapacitors. Recently, liquid exfoliation of bulk metal oxides appears to be an effective route which provides access to two-dimensional (2D) nano-flakes, the size of which can be easily selected. These 2D materials exhibit excellent electrochemical charge storage and catalytic activity for the oxygen evolution reaction. In this study, various sized selected cobalt hydroxide nano-flake materials are fabricated by this time efficient and highly reproducible process. Subsquently, the electrochemical properties of the standard size Co(OH)2 nanoflakes were investigated. The oxide modified electrodes were prepared by spraying the metal oxide flake suspension onto a porous conductive support electrode foam, either glassy carbon or nickel. The cobalt hydroxide/nickel foam system was found to have an overpotential value at 10 mA cm-2 in 1 M NaOH as low as 280 mV and an associated redox capacitance exhibiting numerical values up to 1500 F g-1, thereby making it a viable dual use electrode.

Longitudinal employment outcomes of an early intervention vocational rehabilitation service for people admitted to rehabilitation with a traumatic spinal cord injury.

STUDY DESIGN: Longitudinal cohort design. OBJECTIVES: First, to explore the longitudinal outcomes for people who received early intervention vocational rehabilitation (EIVR); second, to examine the nature and extent of relationships between contextual factors and employment outcomes over time. SETTING: Both inpatient and community-based clients of a Spinal Community Integration Service (SCIS). METHODS: People of workforce age undergoing inpatient rehabilitation for traumatic spinal cord injury were invited to participate in EIVR as part of SCIS. Data were collected at the following three time points: discharge and at 1 year and 2+ years post discharge. Measures included the spinal cord independence measure, hospital anxiety and depression scale, impact on participation and autonomy scale, numerical pain-rating scale and personal wellbeing index. A range of chi square, correlation and regression tests were undertaken to look for relationships between employment outcomes and demographic, emotional and physical characteristics. RESULTS: Ninety-seven participants were recruited and 60 were available at the final time point where 33% (95% confidence interval (CI): 24-42%) had achieved an employment outcome. Greater social participation was strongly correlated with wellbeing (ρ=0.692), and reduced anxiety (ρ=-0.522), depression (ρ=-0.643) and pain (ρ=-0.427) at the final time point. In a generalised linear mixed effect model, education status, relationship status and subjective wellbeing increased significantly the odds of being employed at the final time point. Tertiary education prior to injury was associated with eight times increased odds of being in employment at the final time point; being in a relationship at the time of injury was associated with increased odds of being in employment of more than 3.5; subjective wellbeing, while being the least powerful predictor was still associated with increased odds (1.8 times) of being employed at the final time point. CONCLUSIONS: EIVR shows promise in delivering similar return-to-work rates as those traditionally reported, but sooner. The dynamics around relationships, subjective wellbeing, social participation and employment outcomes require further exploration.

The cross-national epidemiology of specific phobia in the World Mental Health Surveys.

BACKGROUND: Although specific phobia is highly prevalent, associated with impairment, and an important risk factor for the development of other mental disorders, cross-national epidemiological data are scarce, especially from low- and middle-income countries. This paper presents epidemiological data from 22 low-, lower-middle-, upper-middle- and high-income countries. METHOD: Data came from 25 representative population-based surveys conducted in 22 countries (2001-2011) as part of the World Health Organization World Mental Health Surveys initiative (n = 124 902). The presence of specific phobia as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition was evaluated using the World Health Organization Composite International Diagnostic Interview. RESULTS: The cross-national lifetime and 12-month prevalence rates of specific phobia were, respectively, 7.4% and 5.5%, being higher in females (9.8 and 7.7%) than in males (4.9% and 3.3%) and higher in high- and higher-middle-income countries than in low-/lower-middle-income countries. The median age of onset was young (8 years). Of the 12-month patients, 18.7% reported severe role impairment (13.3-21.9% across income groups) and 23.1% reported any treatment (9.6-30.1% across income groups). Lifetime co-morbidity was observed in 60.5% of those with lifetime specific phobia, with the onset of specific phobia preceding the other disorder in most cases (72.6%). Interestingly, rates of impairment, treatment use and co-morbidity increased with the number of fear subtypes. CONCLUSIONS: Specific phobia is common and associated with impairment in a considerable percentage of cases. Importantly, specific phobia often precedes the onset of other mental disorders, making it a possible early-life indicator of psychopathology vulnerability.

Craniosynostosis and risk factors related to thyroid dysfunction.

Thyroid disease is a common problem among women of reproductive age but often goes undiagnosed. Maternal thyroid disease has been associated with increased risk of craniosynostosis. We hypothesized that known risk factors for thyroid disease would be associated with risk of craniosynostosis among women not diagnosed with thyroid disease. Analyses included mothers of 1,067 cases and 8,494 population-based controls who were interviewed for the National Birth Defects Prevention Study. We used multivariable logistic regression to estimate adjusted odds ratios (AOR) and 95% confidence intervals (CI). After excluding women with diagnosed thyroid disease, younger maternal age (AOR 0.7, 95% CI 0.6-0.9, for <25 years versus 25-29), black or other race-ethnicity (AOR 0.3, 95% CI 0.2-0.4 and AOR 0.6, 95% CI 0.4-0.8, respectively, relative to non-Hispanic whites), fertility medications or procedures (AOR 1.5, 95% CI 1.2-2.0), and alcohol consumption (AOR 0.8, 95% CI 0.7-0.9) were associated with risk of craniosynostosis, based on confidence intervals that excluded 1.0. These associations with craniosynostosis are consistent with the direction of their association with thyroid dysfunction (i.e., younger age, black race-ethnicity and alcohol consumption are associated with reduced risk and fertility problems are associated with increased risk of thyroid disease). This study thus provides support for the hypothesis that risk factors associated with thyroid dysfunction are also associated with risk of craniosynostosis. Improved understanding of the potential association between maternal thyroid function and craniosynostosis among offspring is important given that craniosynostosis carries significant morbidity and that thyroid disease is under-diagnosed and potentially modifiable.

Anxious and non-anxious major depressive disorder in the World Health Organization World Mental Health Surveys.

BACKGROUND: To examine cross-national patterns and correlates of lifetime and 12-month comorbid DSM-IV anxiety disorders among people with lifetime and 12-month DSM-IV major depressive disorder (MDD). METHOD: Nationally or regionally representative epidemiological interviews were administered to 74 045 adults in 27 surveys across 24 countries in the WHO World Mental Health (WMH) Surveys. DSM-IV MDD, a wide range of comorbid DSM-IV anxiety disorders, and a number of correlates were assessed with the WHO Composite International Diagnostic Interview (CIDI). RESULTS: 45.7% of respondents with lifetime MDD (32.0-46.5% inter-quartile range (IQR) across surveys) had one of more lifetime anxiety disorders. A slightly higher proportion of respondents with 12-month MDD had lifetime anxiety disorders (51.7%, 37.8-54.0% IQR) and only slightly lower proportions of respondents with 12-month MDD had 12-month anxiety disorders (41.6%, 29.9-47.2% IQR). Two-thirds (68%) of respondents with lifetime comorbid anxiety disorders and MDD reported an earlier age-of-onset (AOO) of their first anxiety disorder than their MDD, while 13.5% reported an earlier AOO of MDD and the remaining 18.5% reported the same AOO of both disorders. Women and previously married people had consistently elevated rates of lifetime and 12-month MDD as well as comorbid anxiety disorders. Consistently higher proportions of respondents with 12-month anxious than non-anxious MDD reported severe role impairment (64.4 v. 46.0%; χ 2 1 = 187.0, p < 0.001) and suicide ideation (19.5 v. 8.9%; χ 2 1 = 71.6, p < 0.001). Significantly more respondents with 12-month anxious than non-anxious MDD received treatment for their depression in the 12 months before interview, but this difference was more pronounced in high-income countries (68.8 v. 45.4%; χ 2 1 = 108.8, p < 0.001) than low/middle-income countries (30.3 v. 20.6%; χ 2 1 = 11.7, p < 0.001). CONCLUSIONS: Patterns and correlates of comorbid DSM-IV anxiety disorders among people with DSM-IV MDD are similar across WMH countries. The narrow IQR of the proportion of respondents with temporally prior AOO of anxiety disorders than comorbid MDD (69.6-74.7%) is especially noteworthy. However, the fact that these proportions are not higher among respondents with 12-month than lifetime comorbidity means that temporal priority between lifetime anxiety disorders and MDD is not related to MDD persistence among people with anxious MDD. This, in turn, raises complex questions about the relative importance of temporally primary anxiety disorders as risk markers v. causal risk factors for subsequent MDD onset and persistence, including the possibility that anxiety disorders might primarily be risk markers for MDD onset and causal risk factors for MDD persistence.