Nivolumab-induced fulminant diabetic ketoacidosis followed by thyroiditis

Five days following the 3rd cycle of nivolumab, a monoclonal antibody, which acts as immune checkpoint inhibitor against the programmed cell death protein-1, for metastatic lung adenocarcinoma, a 56-year-old woman presented at the hospital critically ill. On admission, she had severe diabetic ketoacidosis (DKA), as evidenced by venous glucose of 47 mmol/L, blood ketones of 7.5 mmol/L, pH of 6.95 and bicarbonate of 6.6 mmol/L. She has had no personal or family history of diabetes mellitus (DM), while random venous glucose, measured 1 week prior to hospitalisation, was 6.1 mmol/L. On admission, her HbA1c was 8.2% and anti-GAD antibodies were 12 kIU/L (0–5 kU/L), while islet cell antibodies and serum C-peptide were undetectable. Nivolumab was recommenced without the development of other immune-mediated phenomena until 6 months later, when she developed hypothyroidism with TSH 18 U/L and low free T4. She remains insulin dependent and has required levothyroxine replacement, while she has maintained good radiological and clinical response to immunotherapy. This case is notable for the rapidity of onset and profound nature of DKA at presentation, which occurred two months following commencement of immunotherapy. Despite the association of nivolumab with immune-mediated endocrinopathies, only a very small number of patients developing type 1 DM has been reported to date. Patients should be closely monitored for hyperglycaemia and thyroid dysfunction prior to and periodically during immunotherapy

A prickly problem: developing a volunteer-friendly tool for monitoring populations of a terrestrial urban mammal, the West European hedgehog (Erinaceus europaeus)

Across Europe, hedgehogs (Erinaceus europaeus) appear to be in decline in both urban and rural landscapes. Current methods used to monitor urban populations are, however, associated with several potential limitations. In this study, we conducted hedgehog footprint-tunnel surveys in 219 residential gardens across Reading, UK between May–September in 2013 and/or 2014; gardens were surveyed for five continuous days. Single-species occupancy models were used to investigate factors influencing hedgehog occupancy and two-species occupancy models were used to estimate a species interaction factor (SIF) between hedgehogs and (a) badgers (Meles meles), (b) foxes (Vulpes vulpes) and (c) dogs (Canis familiaris). The five-day survey protocol was associated with a false-absence error rate of 0.1–0.4%, indicating that it was a reliable method for determining hedgehog presence; conversely, 34.7% of householders were not able to correctly predict hedgehog presence or absence. Hedgehogs were widely distributed across Reading, but detected in only 32–40% of gardens. None of the within-garden or outside-garden factors investigated significantly affected hedgehog occupancy in the single-species models, but the two-species models indicated that badgers (SIF = 0.471 ± 0.188), but not foxes (SIF = 0.954 ± 0.048) or dogs (SIF = 0.780 ± 0.228), negatively affected the presence of hedgehogs in gardens, although not significantly. Overall, footprint-tunnels represent a viable field method for monitoring urban hedgehog populations, however, other approaches are required to identify factors that make gardens "hedgehog friendly"

Timescale Dependence in River Channel Migration Measurements

Accurately measuring river meander migration over time is critical for sediment budgets and understanding how rivers respond to changes in hydrology or sediment supply. However, estimates of meander migration rates or streambank contributions to sediment budgets using repeat aerial imagery, maps, or topographic data will be underestimated without proper accounting for channel reversal. Furthermore, comparing channel planform adjustment measured over dissimilar timescales are biased because short‐ and long‐term measurements are disproportionately affected by temporary rate variability, long‐term hiatuses, and channel reversals. We evaluate the role of timescale dependence for the Root River, a single threaded meandering sand‐ and gravel‐bedded river in southeastern Minnesota, USA, with 76 years of aerial photographs spanning an era of landscape changes that have drastically altered flows. Empirical data and results from a statistical river migration model both confirm a temporal measurement‐scale dependence, illustrated by systematic underestimations (2–15% at 50 years) and convergence of migration rates measured over sufficiently long timescales (\u3e 40 years). Frequency of channel reversals exerts primary control on measurement bias for longer time intervals by erasing the record of observable migration. We conclude that using long‐term measurements of channel migration for sediment remobilization projections, streambank contributions to sediment budgets, sediment flux estimates, and perceptions of fluvial change will necessarily underestimate such calculations. © 2019 John Wiley & Sons, Ltd

A citizen science based survey method for estimating the density of urban carnivores

Globally there are many examples of synanthropic carnivores exploiting growth in urbanisation. As carnivores can come into conflict with humans and are potential vectors of zoonotic disease, assessing densities in suburban areas and identifying factors that influence them are necessary to aid management and mitigation. However, fragmented, privately owned land restricts the use of conventional carnivore surveying techniques in these areas, requiring development of novel methods. We present a method that combines questionnaire distribution to residents with field surveys and GIS, to determine relative density of two urban carnivores in England, Great Britain. We determined the density of: red fox (Vulpes vulpes) social groups in 14, approximately 1km2 suburban areas in 8 different towns and cities; and Eurasian badger (Meles meles) social groups in three suburban areas of one city. Average relative fox group density (FGD) was 3.72 km-2, which was double the estimates for cities with resident foxes in the 1980’s. Density was comparable to an alternative estimate derived from trapping and GPS-tracking, indicating the validity of the method. However, FGD did not correlate with a national dataset based on fox sightings, indicating unreliability of the national data to determine actual densities or to extrapolate a national population estimate. Using species-specific clustering units that reflect social organisation, the method was additionally applied to suburban badgers to derive relative badger group density (BGD) for one city (Brighton, 2.41 km-2). We demonstrate that citizen science approaches can effectively obtain data to assess suburban carnivore density, however publicly derived national data sets need to be locally validated before extrapolations can be undertaken. The method we present for assessing densities of foxes and badgers in British towns and cities is also adaptable to other urban carnivores elsewhere. However this transferability is contingent on species traits meeting particular criteria, and on resident responsiveness

Concealed concern: Fathers' experience of having a child with Juvenile Idiopathic Arthritis

Despite increased research into families of chronically ill children, more needs to be known about the father’s experience. We address this issue through asking: ‘What is it like to be the father of a child with juvenile idiopathic arthritis?’ (JIA). Four members of eight families with an adolescent diagnosed with JIA, including seven fathers, were interviewed and transcripts analyzed using grounded theory. This study suggests that fathers of children with JIA experience several severe losses which are exacerbated through comparisons they make between their own situation and that of fathers of healthy children. In addition, the fathers faced several constraints which reduced their opportunities to communicate with their ill child through shared activities. Fathers appeared to conceal their distress by adopting strategies of denial and distraction however their adjustment was facilitated, to some extent, by social support. They could also develop greater acceptance of their situation over time as the care of their ill child became assimilated into family life and constraints upon their life gradually reduced through the increased maturity of their son or daughter with JIA. These findings have implications for healthcare professionals and voluntary organizations

Galleria mellonella as an infection model to investigate virulence of Vibrio parahaemolyticus

This is the final version. Available from Taylor & Francis via the DOI in this recordNon-toxigenic V. parahaemolyticus isolates (tdh-/trh-/T3SS2-) have recently been isolated from patients with gastroenteritis. In this study we report that the larvae of the wax moth (Galleria mellonella) are susceptible to infection by toxigenic or non-toxigenic clinical isolates of V. parahaemolyticus. In comparison larvae inoculated with environmental isolates of V. parahaemolyticus did not succumb to disease. Whole genome sequencing of clinical non-toxigenic isolates revealed the presence of a gene encoding a nudix hydrolase, identified as mutT. A V. parahaemolyticus mutT mutant was unable to kill G. mellonella at 24 h post inoculation, indicating a role of this gene in virulence. Our findings show that G. mellonella is a valuable model for investigating screening of possible virulence genes of V. parahaemolyticus and can provide new insights into mechanisms of virulence of atypical non-toxigenic V. parahaemolyticus. These findings will allow improved genetic tests for the identification of pathogenic V. parahaemolyticus to be developed and will have a significant impact for the scientific community.This work was partly supported by Wellcome Trust Institutional Strategic Support Fund (WT097835MF), Wellcome Trust Multi User Equipment Award (WT097835MF) Medical Research Council Clinical Infrastructure Funding (MR/M008924/1) and Biotechnology and Biological Sciences Research Council (BBSRC) funding (BB/N016513/1)

Training Practices of Academy Rugby League and their alignment to Physical Qualities deemed important for Current and Future Performance

This study aimed to investigate rugby league coaches’ perceptions of physical qualities for current and future performance, while also establishing the training practices of Under-16 and Under-19 players. Twenty-four practitioners (rugby coach, strength and conditioning coach) working within nine Super League clubs completed a questionnaire. The questionnaire required practitioners to rank eleven physical qualities (i.e., strength, power, acceleration, maximum speed, aerobic endurance, change of direction, agility, height, body mass, lean mass and fat mass) by importance for current performance, future performance and career longevity according to playing position (forwards, backs, hookers & halves). Practitioners were asked to provide detail on the frequency and duration of each type of training session completed during a typical week throughout each phase of the season; pre-season, in-season (early), in-season (mid), and in-season (late). Typically, practitioners ranked strength, power and acceleration qualities highest, and endurance and anthropometric qualities lowest. The importance of physical qualities varied according to each playing level and position. Training practices of U16 and U19 players differed during each phase of the season, with U19 players undertaking greater training volumes than U16s players. Overall, the physical qualities coaches perceived as most important were not reflected within their training practices. Rugby league practitioners can use this information as a reference source to design long term athletic development plans, prescribe training and during player development procedures. Moreover, these data can inform and improve training practices while influencing the design of pre-season preparatory phases and in-season periods

Effects of a soft robotic exosuit on the quality and speed of overground walking depends on walking ability after stroke

\ua9 2023, BioMed Central Ltd., part of Springer Nature.Background: Soft robotic exosuits can provide partial dorsiflexor and plantarflexor support in parallel with paretic muscles to improve poststroke walking capacity. Previous results indicate that baseline walking ability may impact a user’s ability to leverage the exosuit assistance, while the effects on continuous walking, walking stability, and muscle slacking have not been evaluated. Here we evaluated the effects of a portable ankle exosuit during continuous comfortable overground walking in 19 individuals with chronic hemiparesis. We also compared two speed-based subgroups (threshold: 0.93 m/s) to address poststroke heterogeneity. Methods: We refined a previously developed portable lightweight soft exosuit to support continuous overground walking. We compared five minutes of continuous walking in a laboratory with the exosuit to walking without the exosuit in terms of ground clearance, foot landing and propulsion, as well as the energy cost of transport, walking stability and plantarflexor muscle slacking. Results: Exosuit assistance was associated with improvements in the targeted gait impairments: 22% increase in ground clearance during swing, 5\ub0 increase in foot-to-floor angle at initial contact, and 22% increase in the center-of-mass propulsion during push-off. The improvements in propulsion and foot landing contributed to a 6.7% (0.04 m/s) increase in walking speed (R 2 = 0.82). This enhancement in gait function was achieved without deterioration in muscle effort, stability or cost of transport. Subgroup analyses revealed that all individuals profited from ground clearance support, but slower individuals leveraged plantarflexor assistance to improve propulsion by 35% to walk 13% faster, while faster individuals did not change either. Conclusions: The immediate restorative benefits of the exosuit presented here underline its promise for rehabilitative gait training in poststroke individuals

Multi-Locus Variable-Number Tandem Repeat Profiling of Salmonella enterica Serovar Typhi Isolates from Blood Cultures and Gallbladder Specimens from Makassar, South-Sulawesi, Indonesia

Multi-locus variable-number tandem repeat analysis differentiated 297 Salmonella enterica serovar Typhi blood culture isolates from Makassar in 76 genotypes and a single unique S. Typhi genotype was isolated from the cholecystectomy specimens of four patients with cholelithiasis. The high diversity in S. Typhi genotypes circulating in Makassar indicates that the number of carriers could be very large, which may complicate disease prevention and control

Antipsychotic dose escalation as a trigger for Neuroleptic Malignant Syndrome (NMS): literature review and case series report

Background: “Neuroleptic malignant syndrome” (NMS) is a potentially fatal idiosyncratic reaction to any medication which affects the central dopaminergic system. Between 0.5% and 1% of patients exposed to antipsychotics develop the condition. Mortality rates may be as high as 55% and many risk factors have been reported. Although rapid escalation of antipsychotic dose is thought to be an important risk factor, to date it has not been the focus of a published case series or scientifically defined. <p/>Aims: To identify cases of NMS and review risk factors for its development with a particular focus on rapid dose escalation in the 30 days prior to onset. <p/>Methodology: A review of the literature on rapid dose escalation was undertaken and a pragmatic definition of “rapid dose escalation” was made. NMS cases were defined using DSM-IV criteria and systematically identified within a secondary care mental health service. A ratio of titration rate was calculated for each NMS patient and “rapid escalators” and “non rapid escalators” were compared. <p/>Results: 13 cases of NMS were identified. A progressive mean dose increase 15 days prior to the confirmed episode of NMS was observed (241.7mg/day during days 1-15 to 346.9mg/day during days 16-30) and the mean ratio of dose escalation for NMS patients was 1.4. Rapid dose escalation was seen in 5/13 cases and non rapid escalators had markedly higher daily cumulative antipsychotic dose compared to rapid escalators. <p/>Conclusions: Rapid dose escalation occurred in less than half of this case series (n=5, 38.5%), although there is currently no consensus on the precise definition of rapid dose escalation. Cumulative antipsychotic dose – alongside other known risk factors - may also be important in the development of NMS