Enhanced EPIRISK tool for rapid epidemic risk analysis.

OBJECTIVES: This study aims to create an enhanced EPIRISK tool in order to correctly predict COVID-19 severity in various countries. The original EPIRISK tool was developed in 2018 to predict the epidemic risk and prioritise response. The tool was validated against nine historical outbreaks prior to 2020. However, it rated many high-income countries that had poor performance during the COVID-19 pandemic as having lower epidemic risk. STUDY DESIGN: This study was designed to modify EPIRISK by reparameterizing risk factors and validate the enhanced tool against different outbreaks, including COVID-19. METHODS: We identified three factors that could be indicators of poor performance witnessed in some high-income countries: leadership, culture and universal health coverage. By adding these parameters to EPIRISK, we created a series of models for the calibration and validation. These were tested against non-COVID outbreaks in nine countries and COVID-19 outbreaks in seven countries to identify the best-fit model. The COVID-19 severity was determined by the global incidence and mortality, which were equally divided into four levels. RESULTS: The enhanced EPIRISK tool has 17 parameters, including seven disease-related and 10 country-related factors, with an algorithm developed for risk level classification. It correctly predicted the risk levels of COVID-19 for all seven countries and all nine historical outbreaks. CONCLUSIONS: The enhanced EPIRSIK is a multifactorial tool that can be widely used in global infectious disease outbreaks for rapid epidemic risk analysis, assisting first responders, government and public health professionals with early epidemic preparedness and prioritising response to infectious disease outbreaks.

Further investigation of lead exposure as a potential threatening process for a scavenging marsupial species.

There is a growing recognition of the harmful effects of lead exposure on avian and mammalian scavengers. This can lead to both lethal and non-lethal effects which may negatively impact wildlife populations. Our objective was to assess medium-term lead exposure in wild Tasmanian devils (Sarcophilus harrisii). Frozen liver samples (n = 41), opportunistically collected in 2017-2022, were analysed using inductively coupled plasma mass spectrometry (ICP-MS) to determine liver lead concentrations. These results were then used to calculate the proportion of animals with elevated lead levels (>5 mg/kg dry weight) and examine the role of explanatory variables that may have influenced the results. The majority of samples analysed were from the south-east corner of Tasmania, within 50 km of Hobart. No Tasmanian devil samples were found to have elevated lead levels. The median liver lead concentration was 0.17 mg/kg (range 0.05-1.32 mg/kg). Female devils were found to have significantly higher liver lead concentrations than males (P = 0.013), which was likely related to lactation, but other variables (age, location, body mass) were not significant. These results suggest that wild Tasmanian devil populations currently show minimal medium-term evidence of exposure to lead pollution, although samples were concentrated in peri-urban areas. The results provide a baseline level which can be used to assess the impact of any future changes in lead use in Tasmania. Furthermore, these data can be used as a comparison for lead exposure studies in other mammalian scavengers, including other carnivorous marsupial species.

Could it be monkeypox? Use of an AI-based epidemic early warning system to monitor rash and fever illness.

OBJECTIVES: The EPIWATCH artificial intelligence (AI) system scans open-source data using automated technology and can be used to detect early warnings of infectious disease outbreaks. In May 2022, a multicountry outbreak of Mpox in non-endemic countries was confirmed by the World Health Organization. This study aimed to identify signals of fever and rash-like illness using EPIWATCH and, if detected, determine if they represented potential Mpox outbreaks. STUDY DESIGN: The EPIWATCH AI system was used to detect global signals for syndromes of rash and fever that may have represented a missed diagnosis of Mpox from 1 month prior to the initial case confirmation in the United Kingdom (7 May 2022) to 2 months following. METHODS: Articles were extracted from EPIWATCH and underwent review. A descriptive epidemiologic analysis was conducted to identify reports pertaining to each rash-like illness, locations of each outbreak and report publication dates for the entries from 2022, with 2021 as a control surveillance period. RESULTS: Reports of rash-like illnesses in 2022 between 1 April and 11 July (n = 656 reports) were higher than in the same period in 2021 (n = 75 reports). The data showed an increase in reports from July 2021 to July 2022, and the Mann-Kendall trend test showed a significant upward trend (P = 0.015). The most frequently reported illness was hand-foot-and-mouth disease, and the country with the most reports was India. CONCLUSIONS: Vast open-source data can be parsed using AI in systems such as EPIWATCH to assist in the early detection of disease outbreaks and monitor global trends.

The Effects of the Paleo Diet on Autoimmune Thyroid Disease: A Mixed Methods Review.

The aim of this systematic review was to examine the characteristics of Paleolithic diet (PD) interventions designed for adult patients with autoimmune thyroid disease (AITD) in order to determine if diet elements have the potential to successfully reduce thyroid antibodies (Ab) such as thyroglobulin (Tg), thyroid peroxidase (TPO), and thyroid stimulating hormone receptor (TSHR), and improve thyroid hormones (thyroxine (T4), triiodothyronine (T3) and thyroid stimulating hormone (TSH)) or resolve AITD pathogenesis. Randomized controlled trials (RCTs) with an adult population of 18 years and older, diagnosed with Hashimoto's thyroiditis (HT) or Graves' disease (GD) (Basedow's), who were placed on a diet of Paleolithic or ancestral nature, and achieved reduction of AITD Abs, improvement of thyroid hormones, and, or resolution of AITD were searched. Various electronic databases were used. Bias was assessed using critical appraisal tools from the Scottish Intercollegiate Guidelines Network (SIGN) and Joanna Briggs Institute (JBI). Studies were excluded according to exclusion criteria and results analyzed. One randomized controlled trial (RCT), a pilot study, and six case studies were found. In total, eight AITD studies focusing on Paleolithic or ancestral interventions were located. In highlight, females were the predominant gender. Case studies solely focused on AITD with protocols ranging from 8-60 weeks. All studies showed clinical improvements, one had significant improvement, two showed AITD resolution. After structured evaluation of nutritional interventions utilizing the PD on the effects of AITD, it was concluded foods of ancestral nature along with the addition of specific supplements, food components, exercise and mindfulness meditation, and exclusion of modern day foods have a considerable impact on thyroid Ab and hormones. The relevant studies suggest while this dietary protocol can be useful in clinical practice, larger-scale studies need to be conducted. Key teaching pointsThere are currently no dietary interventions recommended for the treatment of autoimmune thyroid disease. The Paleo diet has been documented to improve AITD antibodies and thyroid hormones in both Hashimoto's thyroiditis and Graves' disease.The Paleo diet can provide a natural source of nutrients similar to supplemental nutrients that have shown positive results on AITD.The paleo diet provides specific macronutrient percentages that may be beneficial in reducing AITD antibodies, while improving thyroid hormones.Methylation supplementation may be useful in AITD cases.

Child, parent, and family mental health and functioning in Australia during COVID-19: comparison to pre-pandemic data.

The COVID-19 pandemic presents significant risks to population mental health. Despite evidence of detrimental effects for adults, there has been limited examination of the impact of COVID-19 on parents and children specifically. We aim to examine patterns of parent and child (0-18 years) mental health, parent substance use, couple conflict, parenting practices, and family functioning during COVID-19, compared to pre-pandemic data, and to identify families most at risk of poor outcomes according to pre-existing demographic and individual factors, and COVID-19 stressors. Participants were Australian mothers (81%) and fathers aged 18 years and over who were parents of a child 0-18 years (N = 2365). Parents completed an online self-report survey during 'stage three' COVID-19 restrictions in April 2020. Data were compared to pre-pandemic data from four Australian population-based cohorts. Compared to pre-pandemic estimates, during the pandemic period parents reported higher rates of parent depression, anxiety, and stress (Cohen's d = 0.26-0.81, all p < 0.001), higher parenting irritability (d = 0.17-0.46, all p < 0.001), lower family positive expressiveness (d = - 0.18, p < 0.001), and higher alcohol consumption (22% vs 12% drinking four or more days per week, p < 0.001). In multivariable analyses, we consistently found that younger parent age, increased financial deprivation, pre-existing parent and child physical and mental health conditions, COVID-19 psychological and environmental stressors, and housing dissatisfaction were associated with worse parent and child functioning and more strained family relationships. Our data suggest wide-ranging, detrimental family impacts associated with the COVID-19 pandemic; and support policy actions to assist families with financial supports, leave entitlements, and social housing.

Alcohol use among Australian parents during the COVID-19 pandemic - April-2020 to May 2021.

AIMS: This study examined the trajectory of alcohol use frequency among parents from April-2020 to May-2021 during the COVID-19 pandemic in the state of Victoria, Australia (who experienced one of the longest lockdowns in the world), compared to parents from the other states of Australia (who experienced relatively fewer restrictions). We further examined the extent to which baseline demographic factors were associated with changes in alcohol use trajectories among parents. METHOD: Data were from the COVID-19 Pandemic Adjustment Survey (2,261 parents of children 0-18 years). Alcohol use frequency was assessed over 13 waves. Baseline demographic predictors included parent gender, age, speaking a language other than English, number of children, partnership status, education, employment, and income. RESULTS: Overall, alcohol trajectories declined over time. Victorian parents, in comparison to parents from other states, reported a smaller reduction in alcohol use frequency across 2020, with a more notable decline during 2021. Female/other gender, speaking a language other than English at home, unemployment, and lower income (Victoria only) were associated with alcohol trajectories of less frequent use, and older age was associated with a trajectory of more frequent use. CONCLUSIONS: Results suggest subtle difference in alcohol trajectories reflecting COVID-19 restrictions, when comparing Victoria and other states in Australia. Socioeconomically advantaged groups were most at risk for elevated trajectories of alcohol use frequency. Population level support may beneficial to reduce drinking behaviours.

From adolescence to parenthood: a multi-decade study of preconception mental health problems and postpartum parent-infant bonds.

PURPOSE: To examine associations between anxiety and depressive symptoms across adolescence and young adulthood with subsequent maternal- and paternal-infant bonding at 1 year postpartum. METHODS: The data were from a prospective, intergenerational cohort study. Participants (381 mothers of 648 infants; 277 fathers of 421 infants) self-reported depression and anxiety at three adolescent waves (ages 13, 15 and 17 years) and three young adult waves (ages 19, 23 and 27 years). Subsequent parent-infant bonds with infants were reported at 1 year postpartum (parent age 29-35 years). Generalised estimating equations (GEE) separately assessed associations for mothers and fathers. RESULTS: Mean postpartum bonding scores were approximately half a standard deviation lower in parents with a history of persistent adolescent and young adult depressive symptoms (maternal ßadj = - 0.45, 95% CI - 0.69, - 0.21; paternal ßadj = - 0.55, 95% CI - 0.90, 0.20) or anxiety (maternal ßadj = - 0.42, 95% CI - 0.66, - 0.18; paternal ßadj = - 0.49, 95% CI - 0.95, 0.03). Associations were still mostly evident, but attenuated after further adjustment for postpartum mental health concurrent with measurement of bonding. CONCLUSIONS: Persistent symptoms of depression or anxiety spanning adolescence and young adulthood predict poorer emotional bonding with infants 1-year postbirth for both mothers and fathers.

Psychosocial predictors of binge-drinking residual harm in adolescence and young adulthood: Findings from the Australian Temperament Project.

AIMS: We examine the extent to which adolescent and young adult psychosocial factors are associated with variation in the experience of common types of harm (e.g., injuries, violence, sexual regrets) with respect to binge-drinking frequency - termed residual harm. METHODS: Data were from the Australian Temperament Project, a population-based cohort study that has followed a sample of young Australians from infancy to adulthood since 1983. The current sample comprised 1,081 (565 women). Residual harm was operationalised by saving residuals from models regressing number of alcohol harms onto binge-drinking frequency at each of 5 waves, two in adolescence (15-16 and 17-18 years) and three in young adulthood (19-20, 23-24, and 27-28 years). Psychosocial factors (mental health, social skills, quality of parent and peer relationships) were assessed prior to binge drinking in early adolescence (13-14 years) and then again in young adulthood (19-20 years). RESULTS: Adolescent predictors of decreased residual harm were lower depressive symptoms, and higher cooperation, self-control, and peer and parent attachment. Young adult predictors of decreased residual harm were lower depressive, anxiety, and stress symptoms and peer and parent negative appraisal, and higher responsibility, and peer and parent emotional support. Associations were evident in males and females, although the strength of some associations diminished with age. CONCLUSIONS: Adolescents and young adults with better mental health, social skills, and relationship quality experienced less harm with respect to their binge-drinking frequency. Future research should examine the potential of investment in strength-based interventions for young people.

Exploring a causal model in observational cohort data: The role of parents and peers in shaping substance use trajectories.

AIMS: To explore the process of applying counterfactual thinking in examining causal determinants of substance use trajectories in observational cohort data. Specifically, we examine the extent to which quality of the parent-adolescent relationship and affiliations with deviant peers are causally related to trajectories of alcohol, tobacco, and cannabis use across adolescence and into young adulthood. METHODS: Data were drawn from the Australian Temperament Project, a population-based cohort study that has followed a sample of young Australians from infancy to adulthood since 1983. Parent-adolescent relationship quality and deviant peer affiliations were assessed at age 13-14 years. Latent curve models were fitted for past month alcohol, tobacco, and cannabis use (n = 1590) from age 15-16 to 27-28 years (5 waves). Confounding factors were selected in line with the counterfactual framework. RESULTS: Following confounder adjustment, higher quality parent-adolescent relationships were associated with lower baseline cannabis use, but not alcohol or tobacco use trajectories. In contrast, affiliations with deviant peers were associated with higher baseline binge drinking, tobacco, and cannabis use, and an earlier peak in the cannabis use trajectory. CONCLUSIONS: Despite careful application of the counterfactual framework, interpretation of associations as causal is not without limitations. Nevertheless, findings suggested causal effects of both parent-adolescent relationships and deviant peer affiliations on the trajectory of substance use. Causal effects were more pervasive (i.e., more substance types) and protracted for deviant peer affiliations. The exploration of causal relationships in observational cohort data is encouraged, when relevant limitations are transparently acknowledged.

A comparison of longitudinal modelling approaches: Alcohol and cannabis use from adolescence to young adulthood.

BACKGROUND: Modelling trajectories of substance use over time is complex and requires judicious choices from a number of modelling approaches. In this study we examine the relative strengths and weakness of latent curve models (LCM), growth mixture modelling (GMM), and latent class growth analysis (LCGA). DESIGN: Data were drawn from the Australian Temperament Project, a 36-year-old community-based longitudinal study that has followed a sample of young Australians from infancy to adulthood across 16 waves of follow-up since 1983. Models were fitted on past month alcohol use (n = 1468) and cannabis use (n = 549) across six waves of data collected from age 13-14 to 27-28 years. FINDINGS: Of the three model types, GMMs were the best fit. However, these models were limited given the variance of numerous growth parameters had to be constrained to zero. Additionally, both the GMM and LCGA solutions had low entropy. The negative binomial LCMs provided a relatively well-fitting solution with fewer drawbacks in terms of growth parameter estimation and entropy issues. In all cases, model fit was enhanced when using a negative binomial distribution. CONCLUSIONS: Substance use researchers would benefit from adopting a complimentary framework by exploring both LCMs and mixture approaches, in light of the relative strengths and weaknesses as identified. Additionally, the distribution of data should inform modelling decisions.

Optimization of energy transport in the Fenna-Matthews-Olson complex via site-varying pigment-protein interactions.

Energy transport in photosynthetic systems can be tremendously efficient. In particular, we study exciton transport in the Fenna-Mathews-Olson (FMO) complex found in green sulphur bacteria. The exciton dynamics and energy transfer efficiency depend on the interaction of excited chromophores with their environment. Based upon realistic, site-dependent models of the system-bath coupling, we present results that suggest that this interaction may be optimized in the case of FMO. Furthermore we verify two transport pathways and note that one is dominated by coherent dynamics and the other by incoherent energy dissipation. In particular, we note a significant correlation between energy transport efficiency and coherence for exciton transfer from bacteriochlorophyll (BChl) 8 to BChl 4.

Biomimetic sensory feedback through peripheral nerve stimulation improves dexterous use of a bionic hand.

We describe use of a bidirectional neuromyoelectric prosthetic hand that conveys biomimetic sensory feedback. Electromyographic recordings from residual arm muscles were decoded to provide independent and proportional control of a six-DOF prosthetic hand and wrist-the DEKA LUKE arm. Activation of contact sensors on the prosthesis resulted in intraneural microstimulation of residual sensory nerve fibers through chronically implanted Utah Slanted Electrode Arrays, thereby evoking tactile percepts on the phantom hand. With sensory feedback enabled, the participant exhibited greater precision in grip force and was better able to handle fragile objects. With active exploration, the participant was also able to distinguish between small and large objects and between soft and hard ones. When the sensory feedback was biomimetic-designed to mimic natural sensory signals-the participant was able to identify the objects significantly faster than with the use of traditional encoding algorithms that depended on only the present stimulus intensity. Thus, artificial touch can be sculpted by patterning the sensory feedback, and biologically inspired patterns elicit more interpretable and useful percepts.

Nodular rheumatoid arthritis (RA): A distinct disease subtype, initiated by cadmium inhalation inducing pulmonary nodule formation and subsequent RA-associated autoantibody generation.

Nodular rheumatoid arthritis (RA) patients have raised rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) levels, and are more likely to smoke than RA patients without nodules. Subcutaneous and pulmonary rheumatoid nodules (granulomas) frequently co-exist. Pulmonary rheumatoid nodules develop prior to RA development and have the immunological machinery to generate RF and ACPAs. Pulmonary granulomas have been observed in animal models exposed to cadmium (Cd) inhalation. Cigarette smoke increases pulmonary Cd exposure. It has been suggested that dust and cigarette smoke co-exposure increases localised pulmonary Cd adsorption. We hypothesise that subcutaneous nodular RA represents a distinct disease subtype induced by pulmonary rheumatoid nodule formation and the generation of high levels of RA associated autoantibodies initiated by Cd inhalation via cigarette smoke. Cohorts of RA patients attending rheumatology clinics in Cornwall, UK (total n = 504) were studied to determine the prevalence of nodular RA, with matched analysis (age, gender and social class) to compare urinary Cd, RF and ACPA levels stratifying for nodular disease and smoking. In cohort 1 45/303 (14.9%) of the RA patients under regular follow up had nodular disease. Of the RA smokers, 30/155 (19%) were nodular and of the RA non-smokers 15/148 (10%) were nodular. Smoking was significantly associated with nodular RA, odds ratio (OR) = 2.48 95% confidence interval (CI) 1.26-4.88, p = 0.008. Raised urinary Cd levels were significantly associated with nodular RA in non-dust exposed individuals, OR 2.26 (95% CI 1.08-4.73), p = 0.03 compared to dust exposed individuals, OR 0.78 (95% CI 0.35-1.76), p = 0.557, despite fewer pack years (py) at diagnosis (16 vs 20 py). Nodular RA smokers had significantly raised RF levels compared to RA smokers without nodular disease (median RF 171.5 (interquartile range (IQR) 48-394) vs median RF 31.7 (IQR 10.3-170.3), p < 0.00001). RF positivity was significantly more prevalent in nodular RA smokers compared to RA smokers without nodular disease (84/89 (94%) vs. 141/199 (71%), OR = 6.9 (95% CI 2.66-17.91), p < 0.00001). ACPA levels were also significantly raised in nodular smokers compared to non-nodular smokers (median ACPA 250 (IQR 145-426) vs 116 (1-257.5), p < 0.00001), as were ACPA positivity rates (83/89 (93%) vs 123/191 (64%), OR = 7.65 (95% CI 3.17-18.4), p < 0.0001). These pilot results support the hypothesis that nodular RA represents a distinct disease subtype initiated by cadmium inhalation, which we suggest induces pulmonary rheumatoid nodule formation and generation of RA-associated autoantibodies.

The natural history of risky drinking and associated harms from adolescence to young adulthood: findings from the Australian Temperament Project.

BACKGROUND: We aimed to describe the natural history of heavy episodic drinking (HED) and associated harms from adolescence to young adulthood in a large Australian population cohort study. METHOD: The Australian Temperament Project consists of mothers and babies (4-8 months) recruited from Infant Welfare Centres and followed every 2 to 4 years until age 28 years. Analyses were based on data from 1156 young people (497 male; 659 female) surveyed repeatedly at ages 16, 18, 20, 24 and 28 years. We used dual processes latent class growth analysis to estimate trajectories of HED and associated harms, employing a piecewise approach to model the hypothesized rise and subsequent fall across adolescence and the late twenties, respectively. RESULTS: We identified four sex-specific trajectories and observed little evidence of maturing-out across the twenties. In males, a normative pattern of increasing HED across the twenties with little related harm was observed (40% of the male sample). Early and late starter groups that peaked in harms at age 20 years with only minor attenuation in binging thereafter were also observed (6.1% and 35%, respectively). In females, a normative pattern of increasing, but moderate, HED with little related harm was observed (44% of the female sample). Early and late starter groups were also identified (18% and 17%, respectively); however, unlike males, the female late starter group showed a pattern of increasing HED and related harms. CONCLUSIONS: Continued patterns of risky alcohol use and related harms are apparent for both males and females across the twenties.

Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.

Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.

Parental supply of alcohol and alcohol consumption in adolescence: prospective cohort study.

BACKGROUND: Parents are a major supplier of alcohol to adolescents, yet there is limited research examining the impact of this on adolescent alcohol use. This study investigates associations between parental supply of alcohol, supply from other sources, and adolescent drinking, adjusting for child, parent, family and peer variables. METHOD: A cohort of 1927 adolescents was surveyed annually from 2010 to 2014. Measures include: consumption of whole drinks; binge drinking (>4 standard drinks on any occasion); parental supply of alcohol; supply from other sources; child, parent, family and peer covariates. RESULTS: After adjustment, adolescents supplied alcohol by parents had higher odds of drinking whole beverages [odds ratio (OR) 1.80, 95% confidence interval (CI) 1.33-2.45] than those not supplied by parents. However, parental supply was not associated with bingeing, and those supplied alcohol by parents typically consumed fewer drinks per occasion (incidence rate ratio 0.86, 95% CI 0.77-0.96) than adolescents supplied only from other sources. Adolescents obtaining alcohol from non-parental sources had increased odds of drinking whole beverages (OR 2.53, 95% CI 1.86-3.45) and bingeing (OR 3.51, 95% CI 2.53-4.87). CONCLUSIONS: Parental supply of alcohol to adolescents was associated with increased risk of drinking, but not bingeing. These parentally-supplied children also consumed fewer drinks on a typical drinking occasion. Adolescents supplied alcohol from non-parental sources had greater odds of drinking and bingeing. Further follow-up is necessary to determine whether these patterns continue, and to examine alcohol-related harm trajectories. Parents should be advised that supply of alcohol may increase children's drinking.

Restoring motor control and sensory feedback in people with upper extremity amputations using arrays of 96 microelectrodes implanted in the median and ulnar nerves.

OBJECTIVE: An important goal of neuroprosthetic research is to establish bidirectional communication between the user and new prosthetic limbs that are capable of controlling >20 different movements. One strategy for achieving this goal is to interface the prosthetic limb directly with efferent and afferent fibres in the peripheral nervous system using an array of intrafascicular microelectrodes. This approach would provide access to a large number of independent neural pathways for controlling high degree-of-freedom prosthetic limbs, as well as evoking multiple-complex sensory percepts. APPROACH: Utah Slanted Electrode Arrays (USEAs, 96 recording/stimulating electrodes) were implanted for 30 days into the median (Subject 1-M, 31 years post-amputation) or ulnar (Subject 2-U, 1.5 years post-amputation) nerves of two amputees. Neural activity was recorded during intended movements of the subject's phantom fingers and a linear Kalman filter was used to decode the neural data. Microelectrode stimulation of varying amplitudes and frequencies was delivered via single or multiple electrodes to investigate the number, size and quality of sensory percepts that could be evoked. Device performance over time was assessed by measuring: electrode impedances, signal-to-noise ratios (SNRs), stimulation thresholds, number and stability of evoked percepts. MAIN RESULTS: The subjects were able to proportionally, control individual fingers of a virtual robotic hand, with 13 different movements decoded offline (r = 0.48) and two movements decoded online. Electrical stimulation across one USEA evoked >80 sensory percepts. Varying the stimulation parameters modulated percept quality. Devices remained intrafascicularly implanted for the duration of the study with no significant changes in the SNRs or percept thresholds. SIGNIFICANCE: This study demonstrated that an array of 96 microelectrodes can be implanted into the human peripheral nervous system for up to 1 month durations. Such an array could provide intuitive control of a virtual prosthetic hand with broad sensory feedback.

Obliquity Control On Southern Hemisphere Climate During The Last Glacial.

Recent paleoclimate reconstructions have challenged the traditional view that Northern Hemisphere insolation and associated feedbacks drove synchronous global climate and ice-sheet volume during the last glacial cycle. Here we focus on the response of the Patagonian Ice Sheet, and demonstrate that its maximum expansion culminated at 28,400 ± 500 years before present (28.4 ± 0.5 ka), more than 5,000 years before the minima in 65 °N summer insolation and the formally-defined Last Glacial Maximum (LGM) at 21,000 ± 2,000 years before present. To investigate the potential drivers of this early LGM (eLGM), we simulate the effects of orbital changes using a suite of climate models incorporating prescribed and evolving sea-ice anomalies. Our analyses suggest that Antarctic sea-ice expansion at 28.5 ka altered the location and intensity of the Southern Hemisphere storm track, triggering regional cooling over Patagonia of 5 °C that extends across the wider mid-southern latitudes. In contrast, at the LGM, continued sea-ice expansion reduced regional temperature and precipitation further, effectively starving the ice sheet and resulting in reduced glacial expansion. Our findings highlight the dominant role that orbital changes can play in driving Southern Hemisphere glacial climate via the sensitivity of mid-latitude regions to changes in Antarctic sea-ice extent.

Novel mutation in insulin receptor gene identified after muscle biopsy in a Niuean woman with severe insulin resistance.

BACKGROUND: Severe, early-onset insulin resistance in the absence of obesity, hepatic steatosis and dyslipidaemia is frequently attributable to a genetic defect affecting the insulin receptor. We describe a patient with severe insulin resistance in whom insulin receptor mutation analysis was mistakenly recorded as normal. Western blot analysis of skeletal muscle showed reduced insulin receptor protein and led to re-evaluation of the insulin receptor and the discovery of a novel mutation. CASE REPORT: A Niuean women, first evaluated at age 6 years for severe acanthosis nigricans, hirsutism, poor growth and cognitive impairment, had extremely elevated fasting insulin levels of 10740 IU/l (fasting reference range 4-24 IU/l) and a normal glucose concentration (4.9 mmol/l). Diabetes was diagnosed at age 9 years and metformin treatment introduced. By age 14 years, she developed refractory hyperglycaemia despite metformin, rosiglitazone and 240 IU insulin daily. Insulin receptor genetic analysis was documented as normal. At age 23 years, with a blood glucose concentration of 37 mmol/l and an HbA1c concentration of 116 mmol/mol, U500 insulin 2000 IU/day was required for glycaemic control. She developed severe proliferative diabetic retinopathy with neovascular glaucoma leading to blindness. There was no renal dysfunction, dyslipidaemia or hepatic steatosis. A muscle biopsy was performed to evaluate the insulin signalling pathway and showed reduced insulin receptor protein. Sequencing of the insulin receptor showed a homozygous p.Val1010Leu missense mutation. CONCLUSION: This patient illustrates the use of muscle biopsy in the evaluation of a patient with unexplained severe insulin resistance. This approach may usefully be applied to other cases of severe insulin resistance, where genetic testing for known mutations in the insulin signalling pathway has been negative.

Prenatal diagnosis of ductus arteriosus aneurysm.

The ductus arteriosus holds major functional importance within the fetal circulation, and anomalies within the ductus arteriosus may interfere with the integrity of the fetal circulation. Ductus arteriosus aneurysm, previously considered a rare lesion, is now a well-reported finding in infancy with some reports describing this finding in the prenatal period. Postnatally, most ductus arteriosus aneurysms resolve spontaneously; however, a small group of infants show complications such as connective-tissue disorders, thrombo-embolism, compression of surrounding thoracic structures and life-threatening spontaneous rupture requiring surgical correction. As such, postnatal assessment in this group is recommended.