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This study assessed the association between thromboembolic events (TEs) and immune-mediated diseases (IMDs) and characterized the risk profile of TEs among patients with IMDs. An administrative claims database (2014–2018) was used to identify adults with ≥2 diagnoses on different dates for ≥1 IMD (IMD cohort; ankylosing spondylitis, atopic dermatitis, inflammatory bowel disease, multiple sclerosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, and systemic lupus erythematosus); patients without an IMD diagnosis were assigned to the non-IMD cohort. Patients in the IMD cohort were matched 1:1 to patients in the non-IMD cohort on age, sex, and index date. Incremental risk of TE (ie, deep vein thrombosis [DVT], pulmonary embolism [PE], myocardial infarction [MI], and ischemic stroke [IS]) was assessed using adjusted incidence rate ratios (aIRRs) to control for covariates in both cohorts. Risk factors for TEs were assessed in the IMD cohort and included age, female sex, comorbidities, baseline TEs, non-IMD treatments, and IMD treatments. A total of 182,431 patients were included in each cohort (mean age, [51.3] years; 64.3% female). A higher proportion of patients in the IMD cohort versus the non-IMD cohort had ≥1 baseline TE (4.1% vs 2.7%; P < 0.0001). The IMD cohort had a 1.80 (95% CI, 1.68–1.92; P < 0.0001) times higher rate of TEs versus patients in the non-IMD cohort. After adjustments, patients in the IMD cohort had a 1.49 (95% CI, 1.40–1.59; P < 0.0001) times higher rate of TEs versus patients in the non-IMD cohort. Similar results were observed across individual TEs (DVT: aIRR = 1.78; PE: aIRR = 1.66; MI: aIRR = 1.17; IS: aIRR = 1.35; all P < 0.05). Risk factor profiles varied by TE. The greatest risk factor was respective TE during baseline (eg, patients with baseline DVT had 41.1 times the rate of DVT during the study period vs patients without baseline DVT; P < 0.001). Comorbidities, such as cardiovascular diseases, type 2 diabetes, and peripheral vascular disease, were associated with increased rates of MI (IRR = 2.60, 1.30, and 1.54, respectively; all P < 0.05) and IS (IRR = 1.53, 1.54, and 1.24, respectively; all P < 0.05). Janus kinase inhibitors were associated with an increased rate of PE (IRR = 2.52; P < 0.05) and nonsignificant, numerically higher rates of DVT (IRR = 1.23; P = NS) and IS (IRR = 1.82; P = NS). Sphingosine 1-phosphate receptor modulators were associated with decreased rates of TEs (DVT: IRR = 0.61, P = NS; PE: IRR = 0.30, P = NS; MI: IRR = 0.54, P = NS; IS: IRR = 0.33, P < 0.05). The risk of TEs was higher among patients with IMD versus patients without IMD; several factors may affect this risk.

Background Rett syndrome (RTT) is a neurodevelopmental disorder that almost exclusively affects females and is associated with high clinical burden. However, literature characterizing the real-world journey of patients with RTT is limited. This study provided an overview of the epidemiology, patient characteristics, clinical manifestations, healthcare resource utilization (HRU), costs, and treatment patterns of patients with RTT in the US. Methods IQVIA™ Medical Claims Data and Longitudinal Prescription Data (11/01/2016–10/31/2019) were used to identify female patients with RTT, with the first observed diagnosis defined as the index date. Annual incidence and prevalence of RTT were assessed over the entire study period; clinical manifestations, all-cause and RTT-related HRU and costs, and treatment patterns were evaluated during the observation period—from the index date to end of clinical activity or end of data availability, whichever occurred first. Results were further stratified into pediatric (< 18 years) and adult (≥ 18 years) subgroups. Results In 2019, prevalence and incidence of RTT was 0.32 and 0.23 per 10,000 enrollees, respectively. Among 5,940 female patients (pediatric: 3,078; adult: 2,862) with mean observation period of 2.04 years, the most prevalent clinical manifestations were neurological disorders (72.8%), gastrointestinal/nutritional disorders (41.9%), and orthopedic disorders (34.6%). The incidence rate of all-cause HRU was 44.43 visits per-patient-per-year and RTT-related HRU comprised 47% of all-cause HRU. Mean all-cause healthcare costs were $40,326 per-patient-per-year, with medical costs driven by home/hospice care visits, therapeutic services, outpatient visits, and inpatient visits. RTT-related healthcare costs comprised 45% of all-cause healthcare costs. The most prevalent supportive therapy and pharmacologic agent were feeding assistance (37.9%) and antiepileptic drugs (54.8%), respectively. Trends were similar by subgroup; although, rates of HRU were generally higher among pediatric patients relative to adult patients (all-cause: 52.43 and 35.86, respectively), which translated into higher mean healthcare costs (all-cause: $45,718 and $34,548, respectively). Conclusions Patients with RTT have substantial disease burden, including prevalent clinical manifestations, high rates of HRU and annual healthcare costs, and reliance on pharmacologic and supportive therapies. These findings underscore the unmet need for effective therapies to target the multifactorial manifestations of RTT.

Background With the advent of the first targeted therapy for Rett Syndrome (RTT), a comprehensive assessment of the journey of RTT is needed to elucidate on present unmet needs in this population. This study characterized females with RTT in the United States and their disease journey with respect to longitudinal treatment patterns, RTT-related outcomes, and changes in disease severity. Methods This retrospective cohort study used registry data of females with RTT from the 5211 RTT Natural History Study (RNHS) (November 2015–July 2021). Pharmacological and supportive therapy use, RTT-related outcomes, and RTT severity, as measured by the Clinical Severity Scale and Motor Behavioral Assessment scale, were evaluated following the first RNHS visit. Analyses were conducted overall and in subgroups by RTT type (classic and atypical RTT) and age at first visit (pediatric and adult). Results A total of 455 females with RTT were included in the study, of whom 90.5% had classic RTT and 79.8% were pediatric individuals. Over a median follow-up of 4 years, use of pharmacological therapies, including prokinetic agents (42.7% vs. 28.3%), and supportive therapies, including physical therapy (87.3% vs. 40.2%) and speech-language therapy (86.8% vs. 23.9%), were more common in pediatric than adult individuals (all p  < 0.05). Nearly half (44.6%) of all individuals had a hospital or emergency room visit, with a higher proportion of visits in individuals with classic RTT than atypical RTT and pediatric than adult individuals (both p  = 0.001). An increasing trend in clinical severity was observed in pediatric individuals (mean change per year: 0.24; 95% confidence interval [CI]: 0.03, 0.44), while an increasing trend in motor-behavioral dysfunction was observed in pediatric individuals (mean change per year: 1.12; 95% CI: 0.63, 1.60) and those with classic RTT (mean change per year: 0.97; 95% CI: 0.53, 1.41). Conclusions Findings from this study highlight the considerable burden of RTT across disease subtype and age. Despite reliance on supportive therapies and healthcare encounters, individuals with RTT experience increasing disease severity and motor-behavioral dysfunction in childhood and adolescence, underscoring the unmet needs of this population and the value of early intervention to manage RTT in the long-term.

A major component of the Rowan University (RU) engineering program is the clinic course, which gives students the opportunity to work with industrial partners on real projects, while still maintaining a classroom environment. The Blacklight Power (BLP) project consists of the validation of calorimetry results of a novel heat source of an industrial affiliate. Analyzing the results of the calorimetry experiments they performed, following protocols they developed themselves, students demonstrated that their data consistently had less than 1% error. The work involved setting up rigorous protocols, MATLAB programming, Labview data collection and analysis, as well as summarizing the experimental results. These students have experienced, first hand, what is required to bring a potential novel energy source forward. This paper describes how these students were involved as part of their junior and senior clinic course work to be the first group to replicate these results in a third party location outside of the industrial affiliate’s own labs. An important part of the engineering pedagogy at Rowan University is to ensure that students have the benefit of using their engineering skills in an applied manner – to real world challenges. This paper starts with a short background on the clinic program, which provides the skeletal system for this and many other projects. It will then go into a project overview that includes the objective, test setup and procedure which entail how the students used different skills from their engineering background to troubleshoot problems within the project. The next section provides the current results of the students’ work followed by a conclusion and discussion of results. Background The Engineering clinic program at RU provides unique projects and learning environment for its undergraduate students. Traditional lecture courses generally do not provide much practical experience and while they may effectively relate the concepts they teach, they do not provide the experience of applying these concepts the way an open ended problem might. The alternative is providing students with internships, which do take place in a professional environment and work may be tangible to the employer, but generally do not provide for a favorable learning environment. The RU clinic program combines the relative merits of both the classroom environment with the more professional goals of an internship into one course. The students are assigned to a project, generally with an industrial partner or another university, and the students use whatever skills at their disposal towards the goal of that particular project. A wide variety of projects allows students to request projects in areas that are of interest to themselves, rather than generic problems and projects that are focused on demonstrating a particular concept. This program does have real projects where results are expected, but are conducted in more of a classroom environment, with access to engineering faculty members who can provide advice where needed.

A multimodel comparison method is used to assess the sensitivity of Subantarctic Mode Water (SAMW) and Antarctic Intermediate Water (AAIW) formation to climate change. For the Intergovernmental Panel on Climate Change A2 emissions scenario (where atmospheric CO₂ is 860 ppm at 2100), the models show cooling and freshening on density surfaces less than about 27.4 kg m−3, a pattern that has been observed in the late twentieth century. SAMW (defined by the low potential vorticity layer) and AAIW (defined by the salinity minimum layer) warm and freshen as they shift to lighter density classes. Heat and freshwater fluxes at the ocean surface dominate the projected buoyancy gain at outcrop regions of SAMW and AAIW, whereas the net increase in the Ekman flux of heat and freshwater contributes to a lesser extent. This buoyancy gain, combined with shoaling of the winter mixed layer, reduces the volume of SAMW subducted into the ocean interior by a mean of 8 Sv (12%), and the subduction of AAIW decreases by a mean of 14 Sv (23%; 1 Sv ≡ 10⁶ m³ s−1). Decreases in the projected subduction of the key Southern Ocean upper-water masses imply a slow down in the Southern Ocean circulation in the future, driven by surface warming and freshening. A reduction in the subduction of intermediate waters implies a likely future decrease in the capacity of the Southern Ocean to sequester CO₂.

IntroductionInherited retinal diseases (IRD) are a leading cause of visual impairment and blindness in the working age population. Mutations in over 300 genes have been found to be associated with IRDs and identifying the affected gene in patients by molecular genetic testing is the first step towards effective care and patient management. However, genetic diagnosis is currently slow, expensive and not widely accessible. The aim of the current project is to address the evidence gap in IRD diagnosis with an AI algorithm, Eye2Gene, to accelerate and democratise the IRD diagnosis service.Methods and analysisThe data-only retrospective cohort study involves a target sample size of 10 000 participants, which has been derived based on the number of participants with IRD at three leading UK eye hospitals: Moorfields Eye Hospital (MEH), Oxford University Hospital (OUH) and Liverpool University Hospital (LUH), as well as a Japanese hospital, the Tokyo Medical Centre (TMC). Eye2Gene aims to predict causative genes from retinal images of patients with a diagnosis of IRD. For this purpose, 36 most common causative IRD genes have been selected to develop a training dataset for the software to have enough examples for training and validation for detection of each gene. The Eye2Gene algorithm is composed of multiple deep convolutional neural networks, which will be trained on MEH IRD datasets, and externally validated on OUH, LUH and TMC.Ethics and disseminationThis research was approved by the IRB and the UK Health Research Authority (Research Ethics Committee reference 22/WA/0049) ‘Eye2Gene: accelerating the diagnosis of IRDs’ Integrated Research Application System (IRAS) project ID: 242050. All research adhered to the tenets of the Declaration of Helsinki. Findings will be reported in an open-access format.

Changes in the temperature, salinity, and subduction of Subantarctic Mode Water (SAMW) and Antarctic Intermediate Water (AAIW) between the 1950s and 2090s are diagnosed using the CSIRO Mark version 3.5 (Mk3.5) climate system model Caps under a CO₂ forcing that reaches 860 ppm by the year 2100. These Southern Ocean upper-limb water masses ventilate the ocean interior, and changes in their properties have been related to climate change in numerous studies. Over time, the authors follow the low potential vorticity and salinity minimum layers describing SAMW and AAIW and find that the water column in the 2090s shifts to lighter densities by approximately 0.2 kg m−3. The model projects a reduction in the SAMW and AAIW annual mean subduction rates as a result of a combination of a shallower mixed layer, increased potential vorticity at the base of the mixed layer, and a net buoyancy gain. There is little change in the projected total volume of SAMW transported into the ocean interior via the subduction process; however, the authors find a significant decrease in the subduction of AAIW. The authors find overall that increases in the air–sea surface heat and freshwater fluxes mainly control the reduction in the mean loss of the SAMW and AAIW surface buoyancy flux when compared with the effect of changes supplied by Ekman transport because of increased zonal wind stress. In the A2 scenario, there are cooling and freshening on neutral density surfaces less than 27.3 kg m−3in response to the warming and freshening observed at the ocean’s surface. The model projects deepening of density surfaces due to southward shifts in the outcrop regions and the downward displacement of these surfaces north of 45°S. The volume transport across 32°S is predicted to decrease in all three basins, with southward transport of SAMW and AAIW decreasing by up to 1.2 and 2.0 Sv (1 Sv ≡ 10⁶ m³ s−1), respectively, in the Indian Ocean. These projected reductions in the subduction and transport of mode and intermediate water masses in the CSIRO Mk3.5 model could potentially decrease the absorption and storage of CO₂ in the Southern Ocean.