Impact of video vector analysis of ankle foot orthoses in children with physical disability: A 10-year clinical review.

BACKGROUND: Ankle Foot Orthoses (AFOs) are frequently prescribed to manage gait impairments in children with physical disability, and it is important that AFOs are prescribed and fitted appropriately to maximize potential benefits. AFO tuning, manipulation of the AFO footwear combination (AFO-FC) by means of video vector analysis, is routinely used to optimize AFO use. However, the incidence or types of changes that are implemented after this type of orthotic review are unknown. RESEARCH QUESTION: To investigate the impact of a multi-disciplinary video vector clinic on AFO provision in children with physical disability. METHODS: All children who attended a video vector clinic over a period of 10-years from the establishment of the clinic were included in the study. Outcomes of the clinic were grouped into 5 categories: (1) No change to AFO-FC; (2) Altered/tuned AFO-FC; (3) Discontinued AFO-FC; (4) Recast AFO; (5) Change in prescription. Data were summarised narratively. RESULTS: 141 independently ambulant children were included. The diagnoses were bilateral cerebral palsy (39 %, n=55), unilateral cerebral palsy (38 %, n=54), spina bifida (9 %, n=13), hereditary spastic paraparesis (2 %, n=3) and other (11 %, n=16). No changes were made in 52 % of cases (n=74), tuning in 22 % of cases (n=31), the AFO was recast in 13 % of cases (n=19) and discontinued in 10 % of cases (n=14). A prescription change was recommended in 3 % of cases (n=4). SIGNIFICANCE: Our findings suggest that the video vector clinic is a time efficient and effective means of assessing gait function in children with AFOs. Without assessment at the clinic, most of the children assessed would likely have been referred for a full and more time consuming 3-dimensional gait analysis. Video vector analysis at the initial AFO fitting may improve alignment and possibly reduce non-compliance at an earlier stage.

UK Cancer Healthcare Professionals Collaborating With Colleagues in Low- and Middle-Income Countries: Mapping the Extent and Nature of Partnerships; Future Implications.

AIMS: In 2020 the UK Global Cancer Network (UKGCN) was formed to unite those in the UK interested in Global Oncology and to strengthen collaborative partnerships with stakeholders working across low- and middle-income countries (LMICs) in cancer health systems, governance, and care. The UKGCN undertook a mapping exercise to document collaborations to inform the UK's global oncology strategy. MATERIALS AND METHODS: A semi-structured survey was developed and disseminated using a snowball method over ten weeks from February 2021 across the UK's cancer community, to identify individuals and institutions engaged in clinical practice, research, and/or education with partners in LMICs. The survey was sent to individuals in NHS hospitals, charities, universities, other organisations, UKGCN members, and to contacts identified by a literature and web search. RESULTS: A total of 639 invitations were sent, and 88 responses were received. Results demonstrate a range of collaborative efforts spanning many areas of cancer control: health promotion, prevention, diagnosis and treatment, survivorship, and palliative care. A wide range of countries were represented from Sub-Saharan Africa, South America, the MENA region, China, and South-East Asia. The projects included education and training (146), clinical practice/care (144), and research (226). CONCLUSION: This mapping exercise demonstrated considerable UK collaboration with stakeholders in LMICs across all three domains of education, clinical care, and research. The survey results provide an initial framework from which to promote in-depth strategic intelligence on the broad range of activities undertaken by the UK global oncology community. This information has been used as a catalyst to create new partnerships and connect colleagues working in similar geographical settings, encouraging bidirectional learning. The UKGCN will galvanise endeavours to improve equitable access to cancer services globally.

Impact of gene expression profiling on diagnosis and survival after metastasis in patients with uveal melanoma.

Surveillance frequency for metastasis is guided by gene expression profiling (GEP). This study evaluated the effect of GEP on time to diagnosis of metastasis, subsequent treatment and survival. A retrospective study was conducted of 110 uveal melanoma patients with GEP (DecisionDx-UM, Castle Biosciences, Friendswood, Texas, USA) and 110 American Joint Committee on Cancer-matched controls. Surveillance testing and treatment for metastasis were compared between the two groups and by GEP class. Rates of metastasis, overall survival and melanoma-related mortality were calculated using Kaplan-Meier estimates. Baseline characteristics and follow-up time were balanced in the two groups. Patients' GEP classification was 1A in 41%, 1B in 25.5% and 2 in 33.6%. Metastasis was diagnosed in 26.4% ( n  = 29) in the GEP group and 23.6% ( n  = 26) in the no GEP group ( P  = 0.75). Median time to metastasis was 30.5 and 22.3 months in the GEP and no GEP groups, respectively ( P  = 0.44). Median months to metastasis were 34.7, 75.8 and 26.1 in class 1A, 1B and 2 patients, respectively ( P  = 0.28). Disease-specific 5-year survival rates were 89.4% [95% confidence interval (CI): 81.0-94.2%] and 84.1% (95% CI: 74.9-90.1%) in the GEP and no GEP groups respectively ( P  = 0.49). Median time to death from metastasis was 10.1 months in the GEP group and 8.5 months in the no GEP group ( P  = 0.40). There were no significant differences in time to metastasis diagnosis and survival outcomes in patients with and without GEP. To realize the full benefit of GEP, more sensitive techniques for detection of metastasis and adjuvant therapies are required.

Microglial NF-κB Signaling Deficiency Protects Against Metabolic Disruptions Caused by Volatile Organic Compound via Modulating the Hypothalamic Transcriptome.

Prolonged exposure to benzene, a prevalent volatile organic compound (VOC), at concentrations found in smoke, triggers hyperglycemia, and inflammation in mice. Corroborating this with existing epidemiological data, we show a strong correlation between environmental benzene exposure and metabolic impairments in humans. To uncover the underlying mechanisms, we employed a controlled exposure system and continuous glucose monitoring (CGM), revealing rapid blood glucose surges and disturbances in energy homeostasis in mice. These effects were attributed to alterations in the hypothalamic transcriptome, specifically impacting insulin and immune response genes, leading to hypothalamic insulin resistance and neuroinflammation. Moreover, benzene exposure activated microglial transcription characterized by heightened expression of IKKß/NF-κB-related genes. Remarkably, selective removal of IKKß in immune cells or adult microglia in mice alleviated benzene-induced hypothalamic gliosis, and protected against hyperglycemia. In summary, our study uncovers a crucial pathophysiological mechanism, establishing a clear link between airborne toxicant exposure and the onset of metabolic diseases.

Characteristics of a later life population in a general adult community mental health service setting.

OBJECTIVES: Globally, increasing life expectancy has escalated demands on psychiatric services caring for a later life population. It is recognised that those with enduring mental illness may have specific needs with advancing age. In this study, we describe the characteristics of a population aged over 60 years attending a general adult community psychiatric service and compare demographic and clinical features across age and diagnostic categories. The study aims to gather preliminary information which may guide future local mental health service planning. METHODS: We conducted a cross-sectional observational study using retrospective chart review of all patients aged over 60 years attending four community mental health teams in North Dublin. Cohorts of attenders were stratified by age comparing 60-64 year age group with the population aged 65 years and over. Attenders were also stratified by diagnosis and regression analysis was used to determine predictors of psychotic disorder diagnosis. RESULTS: The study included 127 patients. There was a higher prevalence of psychotic disorders among those aged 65 years and over (n = 73), while those aged 60-64 years (n = 54) were more likely to have depression and non-affective, non-psychotic disorders. Among the population aged 65 years and over 78% (n = 57) were long-term psychiatric service attenders. CONCLUSIONS: The majority of the sample aged 65 years and over were long-term service attenders with a diagnosis of severe mental illness. Further research is warranted to determine optimal service delivery for later life psychiatric service attenders.

The medium-term effects of selective dorsal rhizotomy on gait compared to a matched cerebral palsy non-SDR group: A follow-up study.

BACKGROUND: Selective dorsal rhizotomy (SDR) has been shown to improve gait in the short-term in children with cerebral palsy (CP). Further study is needed to look at the trajectory of outcomes over the longer-term. RESEARCH QUESTION: What are the medium-term effects of SDR on gait compared to a matched CP non-SDR group? METHODS: Participants underwent SDR at mean age 6.3 years and completed baseline, 1-year and 5-year follow-up gait analyses. Non-SDR participants were matched at baseline. Differences were assessed within and between groups. Kinematic variables were analysed using Statistical non-Parametric Mapping (SnPM). Other gait and clinical data were analysed using Friedman's one-way repeated measure analysis of variance and a Mann-Whitney U-test. RESULTS: The initial SDR group consisted of 29 participants, reducing to 22 at 5-year follow-up. Of these, 15 (68 %) had orthopaedic surgeries either concurrent with or in the intervening period since the SDR, mean 3.3 procedures per participant. The initial non- SDR group had 18 participants, reducing to 17 at 5-year follow-up. Of these, 13 (76 %) had orthopaedic surgeries, mean 5.7 procedures. At 1-year follow-up the SDR group had significantly improved knee extension, ankle dorsiflexion, foot progression, Gait Deviation Index, and normalised step length compared to baseline, p < 0.05, and outcomes were maintained at 5-years. At 1-year follow-up the non-SDR group kinematic patterns were unchanged, but at 5-year follow-up this group demonstrated significantly improved knee extension, ankle dorsiflexion and foot progression. There were no significant kinematic differences between the SDR and the non-SDR group at medium-term follow-up. SIGNIFICANCE: We have documented the trajectory of gait outcomes post-SDR over 3 assessments and found that short-term gait changes endured in the medium-term. However, kinematic changes were similar to a non-SDR group undergoing routine and orthopaedic care. These outcomes are important to guide surgical decision making and to manage treatment goals and expectations.

Cancer care for Ukrainian refugees: Strategic impact assessments in the early days of the conflict.

BACKGROUND: The invasion of Ukraine by Russia in February 2022 has resulted in destruction of healthcare infrastructure and triggered the largest wave of internally displaced populations and refugees since World War Two. Conflicts in transitioned countries such as Ukraine create new non-communicable disease (NCD) challenges, especially for cancer care for refugees and humanitarian assistance in host countries. In the early days, rapid attempts were made to model possible impacts. METHODS: By evaluating open source intelligence used in the first three months of the conflict through snowball search methods, we aimed to address: (i) burden of cancer in Ukrainian population, specifically considering translating to the refugees population, and its cancer care capacity; ii) baseline capacity/strengths of cancer systems in initial host countries. Moreover, using a baseline scenario based on crude cancer incidence in Ukraine, and considering data from UNHCR, we estimated how cancer cases would be distributed across host countries. Finally, a surveillance assessment instrument was created, intersecting health system's capacity and influx of internally displaced populations and refugees. FINDINGS AND CONCLUSIONS: The total new cancer patients per month in pre-conflict Ukraine was estimated as 13,106, of which < 1 % are paediatric cases. The estimated cancer cases in the refugee population (combining prevalent and incident), assuming 7.5 million refugees by July 2022 and a female:male ratio of 9:1, was 33,121 individuals (Poland: 19284; Hungary: 3484; Moldova: 2651; Slovakia: 2421; Romania: 5281). According to our assessments, Poland is the only neighbouring country classified as green/yellow for cancer capacity, i.e. sufficient ablility to absorb additional burden into national health system; Slovakia we graded as yellow, Hungary and Romania as yellow/red and Moldova as red.

Dust, Sand, and Winds Within an Active Martian Storm in Jezero Crater.

Rovers and landers on Mars have experienced local, regional, and planetary-scale dust storms. However, in situ documentation of active lifting within storms has remained elusive. Over 5-11 January 2022 (LS 153°-156°), a dust storm passed over the Perseverance rover site. Peak visible optical depth was ∼2, and visibility across the crater was briefly reduced. Pressure amplitudes and temperatures responded to the storm. Winds up to 20 m s-1 rotated around the site before the wind sensor was damaged. The rover imaged 21 dust-lifting events-gusts and dust devils-in one 25-min period, and at least three events mobilized sediment near the rover. Rover tracks and drill cuttings were extensively modified, and debris was moved onto the rover deck. Migration of small ripples was seen, but there was no large-scale change in undisturbed areas. This work presents an overview of observations and initial results from the study of the storm.

Single-agent anti-PD-1 or combined with ipilimumab in patients with mucosal melanoma: an international, retrospective, cohort study.

BACKGROUND: Mucosal melanoma (MM) is a rare melanoma subtype with distinct biology and poor prognosis. Data on the efficacy of immune checkpoint inhibitors (ICIs) are limited. We determined the efficacy of ICIs in MM, analyzed by primary site and ethnicity/race. PATIENTS AND METHODS: A retrospective cohort study from 25 cancer centers in Australia, Europe, USA and Asia was carried out. Patients with histologically confirmed MM were treated with anti-programmed cell death protein 1 (PD-1) ± ipilimumab. Primary endpoints were response rate (RR), progression-free survival (PFS), overall survival (OS) by primary site (naso-oral, urogenital, anorectal, other), ethnicity/race (Caucasian, Asian, Other) and treatment. Univariate and multivariate Cox proportional hazards model analyses were conducted. RESULTS: In total, 545 patients were included: 331 (63%) Caucasian, 176 (33%) Asian and 20 (4%) Other. Primary sites included 113 (21%) anorectal, 178 (32%) urogenital, 206 (38%) naso-oral and 45 (8%) other. Three hundred and forty-eight (64%) patients received anti-PD-1 and 197 (36%) anti-PD-1/ipilimumab. RR, PFS and OS did not differ by primary site, ethnicity/race or treatment. RR for naso-oral was numerically higher for anti-PD-1/ipilimumab [40%, 95% confidence interval (CI) 29% to 54%] compared with anti-PD-1 (29%, 95% CI 21% to 37%). Thirty-five percent of patients who initially responded progressed. The median duration of response (mDoR) was 26 months (95% CI 18 months-not reached). Factors associated with short PFS were Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥3 (P < 0.01), lactate dehydrogenase (LDH) more than the upper limit of normal (ULN) (P = 0.01), lung metastases (P < 0.01) and ≥1 previous treatments (P < 0.01). Factors associated with short OS were ECOG PS ≥1 (P < 0.01), LDH >ULN (P = 0.03), lung metastases (P < 0.01) and ≥1 previous treatments (P < 0.01). CONCLUSIONS: MM has poor prognosis. Treatment efficacy of anti-PD-1 ± ipilimumab was similar and did not differ by ethnicity/race. Naso-oral primaries had numerically higher response to anti-PD-1/ipilimumab, without difference in survival. The addition of ipilimumab did not show greater benefit over anti-PD-1 for other primary sites. In responders, mDoR was short and acquired resistance was common. Other factors, including site and number of metastases, were associated with survival.

Cosmic Birefringence from the Planck Data Release 4.

We search for the signature of parity-violating physics in the cosmic microwave background, called cosmic birefringence, using the Planck data release 4. We initially find a birefringence angle of ß=0.30°±0.11° (68% C.L.) for nearly full-sky data. The values of ß decrease as we enlarge the Galactic mask, which can be interpreted as the effect of polarized foreground emission. Two independent ways to model this effect are used to mitigate the systematic impact on ß for different sky fractions. We choose not to assign cosmological significance to the measured value of ß until we improve our knowledge of the foreground polarization.

Industry Funding of Oncology Randomised Controlled Trials: Implications for Design, Results and Interpretation.

AIMS: Most randomised controlled trials (RCTs) in oncology are now funded by the pharmaceutical industry. We explore the extent to which RCT design, results and interpretation differ between industry-funded and non-industry-funded RCTs. MATERIALS AND METHODS: In this cross-sectional analysis, a structured literature search was used to identify all oncology RCTs published globally during 2014-2017. Industry funding was identified based on explicit statements in the publication. Descriptive statistics were used to compare elements of trial methodology and output between industry- and non-industry-funded RCTs. RESULTS: The study sample included 694 RCTs; 71% were funded by industry. Industry-funded trials were more likely to test systemic therapy (97% versus 62%; P < 0.001), palliative-intent therapy (71% versus 41%; P < 0.001) and study breast cancer (20% versus 12%; P < 0.001). Industry-funded trials were larger (median sample size 474 versus 375; P < 0.001) and more likely to meet their primary end point (49% versus 41%; P < 0.001). Among positive trials, there were no differences in the magnitude of benefit between industry- and non-industry-funded RCTs. Trials funded by industry were published in journals that had a significantly higher median impact factor (21, interquartile range 7, 28) than non-industry-funded trials (impact factor 12, interquartile range 5, 24; P = 0.005); this persisted when adjusted for whether a trial was positive or negative. CONCLUSIONS: The vast majority of oncology RCTs are now funded by industry. Industry-funded trials are larger, more likely to be positive, predominantly test systemic therapies in the palliative setting and are published in higher impact journals than trials without industry support.

Winds at the Mars 2020 Landing Site. 2. Wind Variability and Turbulence.

Wind speeds measured by the Mars 2020 Perseverance rover in Jezero crater were fitted as a Weibull distribution. InSight wind data acquired in Elysium Planitia were also used to contextualize observations. Jezero winds were found to be much calmer on average than in previous landing sites, despite the intense aeolian activity observed. However, a great influence of turbulence and wave activity was observed in the wind speed variations, thus driving the probability of reaching the highest wind speeds at Jezero, instead of sustained winds driven by local, regional, or large-scale circulation. The power spectral density of wind speed fluctuations follows a power-law, whose slope deviates depending on the time of day from that predicted considering homogeneous and isotropic turbulence. Daytime wave activity is related to convection cells and smaller eddies in the boundary layer, advected over the crater. The signature of convection cells was also found during dust storm conditions, when prevailing winds were consistent with a tidal drive. Nighttime fluctuations were also intense, suggesting strong mechanical turbulence. Convective vortices were usually involved in rapid wind fluctuations and extreme winds, with variations peaking at 9.2 times the background winds. Transient high wind events by vortex-passages, turbulence, and wave activity could be driving aeolian activity at Jezero. We report the detection of a strong dust cloud of 0.75-1.5 km in length passing over the rover. The observed aeolian activity had major implications for instrumentation, with the wind sensor suffering damage throughout the mission, probably due to flying debris advected by winds.

Lifting and Transport of Martian Dust by the Ingenuity Helicopter Rotor Downwash as Observed by High-Speed Imaging From the Perseverance Rover.

Martian atmospheric dust is a major driver of weather, with feedback between atmospheric dust distribution, circulation changes from radiative heating and cooling driven by this dust, and winds that mobilize surface dust and distribute it in the atmosphere. Wind-driven mobilization of surface dust is a poorly understood process due to significant uncertainty about minimum wind stress and whether the saltation of sand particles is required. This study utilizes video of six Ingenuity helicopter flights to measure dust lifting during helicopter ascents, traverses, and descents. Dust mobilization persisted on takeoff until the helicopter exceeded 3 m altitude, with dust advecting at 4-6 m/s. During landing, dust mobilization initiated at 2.3-3.6 m altitude. Extensive dust mobilization occurred during traverses at 5.1-5.7 m altitude. Dust mobilization threshold friction velocity of rotor-induced winds during landing is modeled at 0.4-0.6 m/s (factor of two uncertainty in this estimate), with higher winds required when the helicopter was over undisturbed terrain. Modeling dust mobilization from >5 m cruising altitude indicates mobilization by 0.3 m/s winds, suggesting nonsaltation mechanisms such as mobilization and destruction of dust aggregates. No dependence on background winds was seen for the initiation of dust lifting but one case of takeoff in 7 m/s winds created a track of darkened terrain downwind of the helicopter, which may have been a saltation cluster. When the helicopter was cruising at 5-6 m altitude, recirculation was seen in the dust clouds.

Clinician Specialty, Access to Care, and Outcomes Among Patients with Peripheral Artery Disease.

BACKGROUND: Understanding the relationship between patterns of peripheral artery disease and outcomes is an essential step toward improving care and outcomes. We hypothesized that clinician specialty would be associated with occurrence of major adverse vascular events (MAVE). METHODS: Patients with at least 1 peripheral artery disease-related encounter in our health system and fee-for-service Medicare were divided into groups based on the specialty of the clinician (ie, cardiologist, surgeon, podiatrist, primary care, or other) providing a plurality of peripheral artery disease-coded care in the year prior to index encounter. The primary outcome was MAVE (a composite of all-cause mortality, myocardial infarction, stroke, lower extremity revascularization, and lower extremity amputation). RESULTS: The cohort included 1768 patients, of whom 30.0% were Black, 23.9% were Medicaid dual-enrollment eligible, and 31.1% lived in rural areas. Patients receiving a plurality of their care from podiatrists had the highest 1-year rates of MAVE (34.4%, P <.001), hospitalization (65.9%, P <.001), and amputations (22.6%, P <.001). Clinician specialty was not associated with outcomes after adjustment. Patients who were Medicaid dual-eligible had higher adjusted risks of mortality (adjusted hazard ratio [HRadj] 1.54, 95% confidence interval [CI] 1.11-2.14) and all-cause hospitalization (HRadj 1.20, 95% CI 1.03-1.40) and patients who were Black had a higher adjusted risk of amputation (HRadj 1.49, 95% CI 1.03-2.15). CONCLUSIONS: Clinician specialty was not associated with worse outcomes after adjustment, but certain socioeconomic factors were. The effects of clinician specialty and socioeconomic status were likely attenuated by the fact that all patients in this study had health insurance; these analyses require confirmation in a more representative cohort.

The association of healthcare disparities and patient-specific factors on clinical outcomes in peripheral artery disease.

BACKGROUND: PAD increases the risk of cardiovascular mortality and limb loss, and disparities in treatment and outcomes have been described. However, the association of patient-specific characteristics with variation in outcomes is less well known. METHODS: Patients with PAD from Duke University Health System (DUHS) between January 1, 2015 and March 31, 2016 were identified. PAD status was confirmed through ground truth adjudication and predictive modeling using diagnosis codes, procedure codes, and other administrative data. Symptom severity, lower extremity imaging, and ankle-brachial index (ABI) were manually abstracted from the electronic health record (EHR). Data was linked to Centers for Medicare and Medicaid Services data to provide longitudinal follow up. Primary outcome was major adverse vascular events (MAVE), a composite of all-cause mortality, myocardial infarction (MI), stroke, lower extremity revascularization and amputation. RESULTS: Of 1,768 patients with PAD, 31.6% were asymptomatic, 41.2% had intermittent claudication (IC), and 27.3% had chronic limb-threatening ischemia (CLTI). At 1 year, patients with CLTI had higher rates of MAVE compared with asymptomatic or IC patients. CLTI and Medicaid dual eligibility were independent predictors of mortality. CLTI and Black race were associated with amputation. CONCLUSIONS: Rates of MAVE were highest in patients with CLTI, but patients with IC or asymptomatic disease also had high rates of adverse events. Black and Medicaid dual-eligible patients were disproportionately present in the CLTI subgroup and were at higher risk of amputation and mortality, respectively. Future studies must focus on early identification of high-risk patient groups to improve outcomes in patients with PAD.