Measurement protocols and determinants of peak oxygen consumption in adults with Down syndrome: a systematic review.

This systematic review aimed to provide an overview of test protocols used to measure peak oxygen uptake (VO2peak) in adults with Down syndrome (DS) and to determine how generalisable the outcomes are for the entire population of adults with DS by describing the sample characteristics of these studies and their impact on VO2peak. A literature search (PROSPERO CRD42022309560) was performed (18 July 2023) using the following databases: PubMed, CINAHL, APA PsycINFO, Web of Science, Embase and SPORTDiscus. For articles to be included, they had to be peer-reviewed pubications, reporting VO2peak or VO2max for individuals with DS separately, with a sample of n ≥ 5 and a mean age ≥18 years. Systematic reviews and meta-analyses were excluded but their reference lists were searched for additional papers to include. Studies were evaluated for risk of bias following the guidelines of Kmet et al. The results were summarised with frequency statistics. Forty-three studies were included in this systematic review. Sample sizes of included adults with DS ranged from n = 4-226, with a total of n = 1498 adults with DS being included. Most studies (29/43) used the same standardised maximal exercise treadmill protocol to measure VO2peak in adults with DS, and 33 out of 43 studies used at least one objective criterion to determine a valid maximal effort. Participants were predominantly male, under 40 years old, and overweight or obese. Additionally, the diversity of study samples was lacking or not reported. The most widely used, standardised, maximal exercise test treadmill protocol is recommended for future use in research and practice, including objective criteria to determine valid maximal effort. The current study samples are not representative of the population of adults with DS in terms of sex, age and diverse backgrounds and therefore likely overestimate VO2peak of this population.

Performance and health of broiler chickens fed low erucic acid, lower fiber pennycress (CoverCressTM) grain.

CoverCress (low erucic acid, lower fiber pennycress) is being developed as a cover crop to be planted in the fall after corn and harvested in the spring prior to planting soybeans. Two experiments were conducted to evaluate 2 lines of the whole grain (CCWG-1: natural mutation and mutation breeding; CCWG-2: gene edited) and the whole grain pretreated with the potential palatability agent copper sulfate (CCWG-1-CuSO4; CCWG-2-CuSO4) as an ingredient for broilers. In Experiment 1, CCWG-1-CuSO4 was included in the diet at 0, 4, and 6% for 41 d. Feed intake, body weight gain, feed conversion, processing characteristics, organ weights, serum thyroid, macropathology and histology data were collected. In Experiment 2, broilers were fed diets containing Control, 2% CCWG-1, 4% CCWG-1, 4% CCWG-2, and 4.35% CCWG-1-CuSO4 for 42 d. Feed intake, body weight gain, feed conversion, organ weights, serum thyroid, blood chemistries, macropathology, and histology data were collected. In Experiment 1, feed intake and body weight were diminished with no effect on feed conversion for the birds consuming diets containing CCWG-1-CuSO4. In Experiment 2, feed intake and body weight were lower with no difference in feed conversion in birds fed diets containing greater than 2% CoverCress grain during d 0 to 28. During d 28 to 42 no difference in feed intake, body weight and an improvement in feed conversion was observed in birds fed all of the CoverCress grain products. In both experiments no significant negative effects were observed in processing, liver, kidney, and thyroid weights, T3, T4, blood chemistries, macropathology, and histopathology between the control and any of the CoverCress grain treatments. No difference in performance was observed in birds fed the mutant (4% CCWG-1) and gene-edited (4% CCWG-2) products. Pretreating CoverCress grain with copper sulfate did not have a significant effect on improving palatability. In conclusion, CoverCress grain can be safely fed to broilers when included at a target rate of 4% in diets and with total glucosinolate levels not to exceed 4.9 µmoles g-1.

The benefits of index telephone consultations in patients referred on the two-week wait colorectal cancer pathway.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic led to hospitals in the UK substituting face-to-face (FtF) clinics with virtual clinic (VC) appointments. We evaluated the use of virtual two-week wait (2-ww) lower gastrointestinal (LGI) clinic appointments, conducted using telephone calls at a district general hospital in England. METHODS: Patients undergoing index outpatient 2-ww LGI clinic assessment between 1 June 2019 and 31 October 2019 (FtF group) and 1 June 2020 and 31 October 2020 (VC group) were identified. Relevant data were obtained using electronic patient records. Compliance with national cancer waiting time targets was assessed. Environmental and financial impact analyses were performed. RESULTS: In total, 1,531 patients were analysed (median age=70, male=852, 55.6%). Of these, 757 (49.4%) were assessed virtually via telephone; the remainder were seen FtF (n=774, 50.6%). Ninety-two (6%, VC=44, FtF=48) patients had malignant pathology and 64 (4.2%) had colorectal cancer (CRC); of these, 46 (71.9%, VC=26, FtF=20) underwent treatment with curative intent. The median waiting times to index appointment, investigation and diagnosis were significantly lower following VC assessment (p<0.001). The cancer detection rates (p=0.749), treatments received (p=0.785) and median time to index treatment for CRC patients (p=0.156) were similar. A significantly higher proportion of patients were seen within two weeks of referral in the VC group (p<0.001). VC appointments saved patients a total of 9,288 miles, 0.7 metric tonnes of CO2 emissions and £7,482.97. Taxpayers saved £80,242.00 from VCs. No formal complaints were received from patients or staff in the VC group. CONCLUSION: Virtual 2-ww LGI clinics were effective, safe and were associated with tangible environmental and financial benefits.

Evaluating the measures in patient-reported outcomes, values and experiences (EMPROVE study): a collaborative audit of PROMs practice in orthopaedic care in the United Kingdom.

INTRODUCTION: All national orthopaedic societies advocate the use of patient reported outcome measures (PROMs), but clear guidance on their use is limited. We utilised a collaborative methodology to perform a national audit aiming to assess the perceived variability in PROMs practice in orthopaedic surgery in the United Kingdom. METHODS: A multicentre collaborative audit of practice was performed extracting PROMs data on 21 commonly performed orthopaedic procedures. For each procedure, data were collected for frequency of PROM collection, type of PROM chosen, administration intervals, method and reason for collection. Compliance with national society recommendations was undertaken. RESULTS: Sixty-three trusts enrolled to participate in the study with a completion rate of 60% (38 trusts). The most frequently reported PROMs were those associated with best practice tariffs (83.3% and 80.6% for hip and knee replacements, respectively). Outside incentivised programmes we observed a higher rate of variation in PROMs practice which failed to meet our audit standard. Across all procedures evaluated, 69% (221/318) of respondents to the study used paper as the primary method of PROM collection. CONCLUSIONS: This is the first national audit of PROMs collection in orthopaedics. The integration of PROMs within best practice tariff platforms positively influences the frequency and standardisation of collection. Outside this initiative, PROMS collection is infrequent and highly varied despite the presence of several registries. Because PROMs collection is a recommendation across all procedures using implantable devices, the success of this will depend on the adequacy of funding, resource delivery and the presence of clearer recommendations.

Tolerability of graded levels of tall oil fatty acids as a nutritional additive for broiler chickens: a 45-day target animal safety study.

1. The following study was conducted to evaluate the tolerability of tall oil fatty acid (TOFA) to broiler chickens, at three graded levels as a nutritional additive in complete feed.2. 256 one-day-old female and male Cobb 500 broiler chickens were assigned to four dietary treatment groups with TOFA at 0 (control), 1.0, 3.0, or 5.0 g/kg within a complete feed for 45 d.3. Birds were weighed individually on days 0, 16, 31 and 45, and the feed intake, bird weight gain, and feed conversion ratio were calculated for the respective starter, grower and finisher phases and over the whole study. On day 45, blood samples were drawn from each bird for haematology and blood chemistry measurements. Two birds per pen were subjected to gross pathological examination and sampling of several tissues for histopathology, including weighing the liver.4. The dietary treatments did not affect zootechnical performance variables or mortality over the whole study period. Bird performance was typical for the breed.5. Haematology, clinical chemistry and histopathology did not reveal any changes associated with dietary TOFA dosing. However, the 5.0 g/kg dose level increased the relative weight of the liver, as a percentage of final body weight, compared to the control group, but there was lack of corresponding histopathology findings.6. In conclusion, the study indicated that oral administration of TOFA for 45 d in feed was well tolerated by the birds at dietary levels of up to 5.0 g/kg.

Determining the appropriate use of Technology Enabled Care Services (TECS) to manage upper-limb trauma injuries during the COVID-19 pandemic: A multicentre retrospective observational study.

BACKGROUND: The COVID-19 pandemic created a unique opportunity to explore the use of Technology Enabled Care Services (TECS), which remains novel for many service providers. This study assesses the factors that affect adaptation to remote monitoring of patients after upper-limb trauma injury. A standardised risk-stratified screening tool is further developed here to support clinical staff in both the determination of appropriate use of TECS and the optimisation of patient care. OBJECTIVES: 1: To explore the patient and injury factors that determine the appropriate use of TECS for patients with upper-limb injury. 2: To use these findings to refine a standardised screening tool for the appropriate choice of follow-up format. METHODS: A retrospective review of patient management was undertaken across three NHS upper-limb trauma units during the first UK COVID-19 lockdown. Data were collected, and themes were analysed across a number of predetermined categories. This was underpinned by a review of contemporary policy guidance and literature. RESULTS: A total of 85% of patients were offered an appropriate format of follow-up; this was defined by the ability to achieve desired patient-clinician goals and lack of complications. Key factors in determining appropriate follow-up included extent of injury, mental health considerations, and the need for face-to-face (F2F) assessment and treatment. CONCLUSION: Study findings demonstrate consistency between units in the factors determining the appropriate use of TECS. The refined screening tool provides a risk-stratified, standardised approach to the choice of follow-up format, F2F or TECS. It is hoped that this will support future clinical decision-making processes to ensure optimal patient care.

Child abuse and neglect in a pediatric emergency department: epidemiology and outcome.

INTRODUCTION: Managing child abuse and neglect in pediatric emergency departments (PEDs) is difficult because of the complexity of screening and the prolonged care process. This study's main objective was to measure the child protection activity in a PED. METHODS: A retrospective, single-center study was conducted in the PED of the Lille University Hospital from 16 September∫2017 to 11 February 2019. All patients who required a social evaluation by the PED staff were included. Children admitted at first to the PED but for whom social management was exclusively performed by other units were not included. The whole population was analyzed first and then by type of abuse. The primary endpoint was the rate of patients who needed social management in the PED. The length of stay in the PED, the number of reports for investigation by child protective services, and reports to a judge were secondary assessment criteria. RESULTS: The study involved 245 patients (median age, 5 years; interquartile range [IQR], 2-13; boys, 49%), accounting for 0.6% of the PED visits. The main reasons for visiting the PED were somatic complaints (31%), sexual assault (23%), and behavioral disorders (20%). The median length of care in the PED was 5 h (IQR, 3-13). Thirty-three percent of the patients were monitored in the short-stay unit of the PED; 78% returned home. The main social measures taken were reports to child protective services (34%) and reports to a judge (24%); 51% of the patients required further actions by the PED physician after discharge. CONCLUSION: Management of child abuse in the PED is important and time-consuming. A hospital team specialized in child protection is essential for the initial care and monitoring of child victims.

Beyond Toxin Transport: Novel Role of ABC Transporter for Enzymatic Machinery of Cereulide NRPS Assembly Line.

Nonribosomal peptide synthetases (NRPSs) and polyketide synthetases (PKSs) play a pivotal role in the production of bioactive natural products, such as antibiotics and cytotoxins. Despite biomedical and pharmaceutical importance, the molecular mechanisms and architectures of these multimodular enzyme complexes are not fully understood. Here, we report on an ABC transporter that forms a vital part of the nonribosomal peptide biosynthetic machinery. Emetic Bacillus cereus produces the highly potent, mitochondrial active nonribosomal depsipeptide cereulide, synthesized by the NRPS Ces. The ces gene locus includes, next to the structural cesAB genes, a putative ABC transporter, designated cesCD Our study demonstrates that tethering of CesAB synthetase to the cell membrane by CesCD is critical for peptide assembly. In vivo studies revealed that CesAB colocalizes with CesCD on the cell membrane, suggesting direct involvement of this ABC transporter in the biosynthesis of a nonribosomal peptide. Mutation of cesCD, disrupting the assembly of the CesCD complex, resulted in decreased interaction with CesAB and, as a consequence, negatively affected cereulide biosynthesis. Specific domains within CesAB synthetase interacting with CesC were identified. Furthermore, we demonstrated that the structurally similar BerAB transporter from Bacillus thuringiensis complements CesCD function in cereulide biosynthesis, suggesting that the direct involvement of ABC transporter in secondary metabolite biosynthesis could be a widespread mechanism. In summary, our study revealed a novel, noncanonical function for ABC transporter, which is essential for megaenzyme functionality of NRPS. The new insights into natural product biosynthesis gained may facilitate the discovery of new metabolites with bioactive potential.IMPORTANCE This study revealed a novel, potentially conserved mechanism involved in the biosynthesis of microbial natural products, exemplified by the mitochondrial active depsipeptide cereulide. Similar to other bioactive substances, such as the last-resort antibiotics vancomycin and daptomycin, the antitumor drug cryptophycin or the cholesterol-lowering agent lovastatin, cereulide is synthesized nonribosomally by multienzyme machinery, requiring the concerted actions of multiple proteins to ensure correct product assembly. Given the importance of microbial secondary metabolites in human and veterinary medicine, it is critical to understand how these processes are orchestrated within the host cells. By revealing that tethering of a biosynthetic enzyme to the cell membrane by an ABC transporter is essential for nonribosomal peptide production, our study provides novel insights into synthesis of microbial secondary metabolites, which could contribute to isolation of novel compounds from cryptic secondary metabolite clusters or improve the yield of produced pharmaceuticals.

What do the changing patterns of comorbidity burden in people living with HIV mean for long-term management? Perspectives from European HIV cohorts.

Undoubtedly, comorbidities complicate long-term HIV management and have significant cost implications for healthcare systems. A better understanding of these comorbidities and underlying causes would allow for a more considered and proactive approach to the long-term management of HIV. This review examines cross-sectional analyses of six European cohort studies (Athens Multicenter AIDS Cohort Study, Aquitaine Cohort, EuroSIDA Cohort study, French claims EGB, German InGef Cohort and the Italian Cohort of Individuals, Naïve for Antiretrovirals), which included individuals with HIV followed over a certain period of time. Based on these cohorts, we examined how comorbidities have changed over time; how they compromise HIV management; and how much of a financial burden they impart. These data also provided a framework to explore the major issues of ageing and HIV and the practical implications of managing such issues in real-life practice.

'Everything was just getting worse and worse': deteriorating job quality as a driver of doctor emigration from Ireland.

BACKGROUND: Medicine is a high-status, high-skill occupation which has traditionally provided access to good quality jobs and relatively high salaries. In Ireland, historic underfunding combined with austerity-related cutbacks has negatively impacted job quality to the extent that hospital medical jobs have begun to resemble extreme jobs. Extreme jobs combine components of a good quality job-high pay, high job control, challenging demands, with those of a low-quality job-long working hours, heavy workloads. Deteriorating job quality and the normalisation of extreme working is driving doctor emigration from Ireland and deterring return. METHODS: Semi-structured qualitative interviews were conducted with 40 Irish emigrant doctors in Australia who had emigrated from Ireland since 2008. Interviews were held in July-August 2018. RESULTS: Respondents reflected on their experiences of working in the Irish health system, describing hospital workplaces that were understaffed, overstretched and within which extreme working had become normalised, particularly in relation to long working hours, fast working pace, doing more with less and fighting a climate of negativity. Drawing on Hirschman's work on exit, voice and loyalty (1970), the authors consider doctor emigration as exit and present respondent experiences of voice prior to emigration. Only 14/40 respondent emigrant doctors intend to return to work in Ireland. DISCUSSION: The deterioration in medical job quality and the normalisation of extreme working is a key driver of doctor emigration from Ireland, and deterring return. Irish trained hospital doctors emigrate to access good quality jobs in Australia and are increasingly likely to remain abroad once they have secured them. To improve doctor retention, health systems and employers must mitigate a gainst the emergence of extreme work in healthcare. Employee voice (about working conditions, about patient safety, etc.) should be encouraged and used to inform health system improvement and to mitigate exit.

Critical evaluation of current data analysis strategies for psychophysiological measures of fear conditioning and extinction in humans.

Fear conditioning and extinction is a construct integral to understanding trauma-, stress- and anxiety-related disorders. In the laboratory, associative learning paradigms that pair aversive with neutral stimuli are used as analogues to real-life fear learning. These studies use physiological indices, such as skin conductance, to sensitively measure rates and intensity of learning and extinction. In this review, we discuss some of the potential limitations in interpreting and analysing physiological data during the acquisition or extinction of conditioned fear. We argue that the utmost attention should be paid to the development of modelling approaches of physiological data in associative learning paradigms, by illustrating the lack of replicability and interpretability of results in current methods. We also show that statistical significance may be easily achieved in this paradigm without more stringent data and data analysis reporting requirements, leaving this particular field vulnerable to misleading conclusions. This review is written so that issues and potential solutions are accessible to researchers without mathematical training. We conclude the review with some suggestions that all laboratories should be able to implement, including visualising the full data set in publications and adopting modelling, or at least regression-based, approaches.

Effectiveness of the Cobb-Stainsby excision arthroplasty.

BACKGROUND: Dislocated metatarsophalangeal joints from clawed or hammer toes can be a disabling consequence of several conditions. The Cobb-Stainsby forefoot arthroplasty combines partial phalangectomy (Stainsby) with extensor tendon transfer to the metatarsal head (Cobb). We present a retrospective, three surgeon case series of 215 toes in 126 patients. METHODS: Early results and complications were gathered from the medical charts of 126 patients who met the inclusion criteria. Seventy-five patients were contactable by phone with a follow up range of 12-82 months (median follow up 45 months). Primary outcome measures were improvement of pain and function, reduction in plantar callosities and cosmetic improvement of the deformity. RESULTS: Pre-operatively all patients presented with pain and shoe wear problems. Post-operatively seventy-two patients (96%) were satisfied, 72 (96%) reported pain relief, 55 (73%) were happy with toe control, 61 (81%) were pleased with cosmesis and 56 (75%) reported unlimited daily activities. Superficial wound infections were observed in 13 of the 126 patients (10%) and two in 75 patients (2%) developed recurrent clawing. CONCLUSION: Our case series demonstrates improved outcomes over alternatives such as the Weil's osteotomy.

Cognitive, physical, and mental health outcomes between long-term cannabis and tobacco users.

INTRODUCTION: Cannabis intoxication adversely affects health, yet persistent effects following short-term abstinence in long-term cannabis users are unclear. This matched-subjects, cross-sectional study compared health outcomes of long-term cannabis and long-term tobacco-only users, relative to population norms. METHODS: Nineteen long-term (mean 32.3years of use, mean age 55.7years), abstinent (mean 15h) cannabis users and 16 long-term tobacco users (mean 37.1years of use, mean age 52.9years), matched for age, educational attainment, and lifetime tobacco consumption, were compared on measures of learning and memory, response inhibition, information-processing, sustained attention, executive control, and mental and physical health. RESULTS: Cannabis users exhibited poorer overall learning and delayed recall and greater interference and forgetting than tobacco users, and exhibited poorer recall than norms. Inhibition and executive control were similar between groups, but cannabis users had slower reaction times during information processing and sustained attention tasks. Cannabis users had superior health satisfaction and psychological, somatic, and general health than tobacco users and had similar mental and physical health to norms whilst tobacco users had greater stress, role limitations from emotional problems, and poorer health satisfaction. CONCLUSIONS: Long-term cannabis users may exhibit deficits in some cognitive domains despite short-term abstinence and may therefore benefit from interventions to improve cognitive performance. Tobacco alone may contribute to adverse mental and physical health outcomes, which requires appropriate control in future studies.

Abacavir usage patterns and hypersensitivity reactions in the EuroSIDA cohort.

OBJECTIVES: Five to eight per cent of HIV-positive individuals initiating abacavir (ABC) experience potentially fatal hypersensitivity reactions (HSRs). We sought to describe the proportion of individuals initiating ABC and to describe the incidence and factors associated with HSR among those prescribed ABC. METHODS: We calculated the proportion of EuroSIDA individuals receiving ABC-based combination antiretroviral therapy (cART) among those receiving cART after 1 January 2009. Poisson regression was used to identify demographic, and current clinical and laboratory factors associated with ABC utilization and discontinuation. RESULTS: Between 2009 and 2016, of 10 076 individuals receiving cART, 3472 (34%) had ever received ABC-based cART. Temporal trends of ABC utilization were also heterogeneous, with 28% using ABC in 2009, dropping to 26% in 2010 and increasing to 31% in 2016, and varied across regions and over time. Poisson models showed lower ABC utilization in older individuals, and in those with higher CD4 cell counts, higher cART lines, and prior AIDS. Higher ABC utilization was associated with higher HIV RNA and poor renal function, and was more common in Central-East and Eastern Europe and lowest during 2014. During 779 person-years of follow-up (PYFU) in 2139 individuals starting ABC after 1 January 2009, 113 discontinued ABC within 6 weeks of initiation for any reason [incidence rate (IR) 14.5 (95% confidence interval (CI) 12.1, 17.5) per 100 PYFU], 13 because of reported HSR [IR 0.3 (95% CI 0.1, 1.0) per 100 PYFU] and 35 because of reported HSR/any toxicity [IR 4.5 (95% CI 3.2, 6.3) per 100 PYFU]. There were no factors significantly associated with ABC discontinuation because of reported HSR/any toxicity. CONCLUSIONS: ABC remains commonly used across Europe and the incidence of discontinuation because of reported HSR was low in our study population.

Bone health and SATB2-associated syndrome.

SATB2-associated syndrome (SAS) is a rare disorder caused by alterations in the special AT-rich sequence-binding protein 2 (SATB2). Skeletal abnormalities such as tibial bowing, osteomalacia, osteopenia or osteoporosis have been reported suggesting a higher frequency of skeletal complications in SAS. The optimal timing, necessity, and methodology for routine assessment of bone health in individuals with SAS, however, remain unclear. We report molecular and phenotypic features of 7 individuals with SAS documented to have low bone mineral density (BMD) ascertained by dual-energy X-ray absorptiometry (DXA), often preceded by tibial bowing. The lowest BMD Z-scores ranged -2.3 to -5.6. In 4 individuals, total alkaline phosphatase levels were elevated (2 with elevated bone fraction) around the time of low BMD documentation. A clinically significant fracture history and a diagnosis of pediatric osteoporosis were present in 4 individuals. Pamidronate treatment in 2 children improved BMD. In conclusion, low BMD, fractures, and tibial bowing are relatively common skeletal complications in individuals with SAS. DXA is a useful tool when evaluating a child with SAS suspected to have low BMD and the results might alter clinical management.

Transport and potential attenuation of nitrogen in shallow groundwaters in the lower Rangitikei catchment, New Zealand.

Intensive agricultural activities are generally associated with nitrogen leaching from agricultural soils, and this nitrogen has the potential to percolate and contaminate groundwater and surface waters. We assessed surface water and groundwater interactions, and nitrogen leaching and its potential attenuation in shallow groundwater in the lower Rangitikei River catchment (832km2), New Zealand. We combined regional- and local-scale field surveys and experiments, nutrient budget modelling, and hydraulic and geochemical methods, to gain an insight into leaching, transformation and transport of nitrogen via groundwaters to the river in the study area. Concurrent river flow gaugings (in January 2015) and a piezometric map, developed from measured depths to groundwater in 110 bores (in October 2014), suggest groundwater discharges to the Rangitikei River in the upper parts of the study area, while there is groundwater recharge near the coast. The groundwater redox characterisation, based on sampling and analysis of 15 mostly shallow bores (<30m below ground level (bgl)), suggests groundwater across the lower Rangitikei catchment in general is under anoxic/reduced conditions. The groundwater typically has low dissolved oxygen (DO) concentrations (<1mg/L), suggesting the subsurface environment is conducive to potential attenuation by 'denitrification' of NO3-N in groundwater. We further measured NO3-N attenuation in shallow groundwater piezometers (3-6mbgl) using single-well push-pull tests. We found generally low levels (<0.5mg/L) of NO3-N in shallow groundwater piezometers (>5mbgl), despite being installed under intensive land uses, such as dairying and cropping. Our in-field push-pull tests showed NO3-N reduction at four shallow groundwater piezometers, with the rates of reduction varying from 0.04mgNL-1h-1 to 1.57mgNL-1h-1. This highlights the importance of a sound understanding of not only the sources, but also transport and transformation, or fate, of nutrients leached from farms, to mitigate the likely impacts of land use on water quality and ecosystem health in agricultural catchments.

A de novo mosaic mutation in SPAST with two novel alternative alleles and chromosomal copy number variant in a boy with spastic paraplegia and autism spectrum disorder.

Here we report a 12 year old male with an extreme presentation of spastic paraplegia along with autism and dysmorphisms. Whole exome sequencing identified a predicted pathogenic pair of missense variants in SPAST at the same chromosomal location, each with a different alternative allele, while a chromosome microarray identified a 1.73 Mb paternally inherited copy gain of 1q21.1q21.2 resulting in a blended phenotype of both Spastic paraplegia 4 and 1q21.1 microduplication syndrome. We believe that the extreme phenotype observed is likely caused by the presence of cells which contain only mutant SPAST, but that the viability of the patient is possible due mosaicism of mutant alleles observed in different proportions across tissues.

Statin use and the risk of herpes zoster: a nested case-control study using primary care data from the U.K. Clinical Research Practice Datalink.

BACKGROUND: Statins are commonly prescribed worldwide and recent evidence suggests that they may increase the risk of herpes zoster (HZ). OBJECTIVES: To quantify the effect of statin exposure on the risk of HZ in the U.K. METHODS: A matched case-control study was conducted using data from U.K. primary care and hospital records. Patients > 18 years with an incident diagnosis of HZ were matched to up to four controls for age, sex and general practice. Patients were included in the statin exposure group if they had ever used a statin, and the daily dosage of the most recent statin prescription and the time since the most recent statin prescription were also recorded. The primary outcome was an incident diagnosis of HZ. Odds ratios (ORs) were estimated from conditional logistic regression and adjusted for potential confounders. RESULTS: A total of 144 959 incident cases of HZ were matched to 549 336 controls. Adjusted analysis suggested strong evidence for an increase in the risk of HZ related to statin exposure (OR 1·13, 95% confidence interval 1·11-1·15). There was also an increased risk when dosages were increased for patients who were currently or had recently been receiving statin treatment (Ptrend < 0·001), and we found an attenuation of the increased risk of HZ in previous statin users as the time since last statin exposure increased (Ptrend < 0·001). CONCLUSIONS: These findings are consistent with the hypothesis that statin therapy leads to an increase in the risk of HZ.

The use of technology enhanced learning in health research capacity development: lessons from a cross country research partnership.

BACKGROUND: With the recognition of the need for research capacity strengthening for advancing health and development, this research capacity article explores the use of technology enhanced learning in the delivery of a collaborative postgraduate blended Master's degree in Malawi. Two research questions are addressed: (i) Can technology enhanced learning be used to develop health research capacity?, and: (ii) How can learning content be designed that is transferrable across different contexts? METHODS: An explanatory sequential mixed methods design was adopted for the evaluation of technology enhanced learning in the Masters programme. A number of online surveys were administered, student participation in online activities monitored and an independent evaluation of the programme conducted. RESULTS: Remote collaboration and engagement are paramount in the design of a blended learning programme and support was needed for selecting the most appropriate technical tools. Internet access proved problematic despite developing the content around low bandwidth availability and training was required for students and teachers/trainers on the tools used. Varying degrees of engagement with the tools used was recorded, and the support of a learning technologist was needed to navigate through challenges faced. CONCLUSION: Capacity can be built in health research through blended learning programmes. In relation to transferability, the support required institutionally for technology enhanced learning needs to be conceptualised differently from support for face-to-face teaching. Additionally, differences in pedagogical approaches and styles between institutions, as well as existing social norms and values around communication, need to be embedded in the content development if the material is to be used beyond the pilot resource-intensive phase of a project.