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This paper applies an Intersectionality Based Policy Analysis Framework to Ontario’s current mental health plan – The Roadmap: A Plan to Build Ontario’s Mental Health and Addictions Services – in order to identify the contextual influences, underlying values and assumptions, which promote or undermine the uptake of human rights and equity as a mental health policy priority in Ontario. We found that dominant framings of the “problem” of mental health (as lack of access, coordination or integration, as a fiscal drain, as an economic burden, and as a clinical or medical problem) served to obscure and ignore the underlying social and structural conditions that impact mental health and the human rights violations that routinely occur in the context of “care.” We discuss the implications of The Roadmap ignoring social and structural determinants of health, and by way of contrast, explore how citizen engagement and activism can support rethinking mental health policy so that it is more just and equitable.

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In British Columbia (BC), Canada, mental health reforms over the last decade have moved back and forth between calls for practices that restrict human rights and those that are rooted in equity and social justice. In this article, we explore some of these tensions and their implications for human rights and equity in mental health care by critically analyzing three policies guiding mental health reform in BC using an intersectionality-based policy framework. Specifically, we interrogate the effects of a biomedical and individualized framing of mental health and substance use. We argue that such a framing is buttressed by neoliberal ideology and lays the groundwork for public and professional acceptance of coercive practices with particular consequences for Indigenous and racialized populations. This framing is juxtaposed with a holistic wellness and trauma-informed policy framework anchored by an understanding of the impact of colonization. However, what is missing in both policy framings is a full account of the documented ongoing human rights violations experienced by many people accessing BC’s mental health system. Our analysis shows how applying an intersectionality-based policy framework allows for a deeper exploration of the complex, interlocking systems of power and oppression that give rise to these human rights violations. We conclude with a discussion of the important role that decolonizing and intersectional approaches play for capturing the complexities of systemic inequities and advancing mental healthcare that protects and promotes mental wellbeing and human rights.

The mental health situation in Kenya has been termed a silent epidemic threatening the mental wellbeing of the population. Deeply entrenched stigma and discrimination is systematic and directly influences access to mental health care, human rights violations, and social exclusion. Despite commitments to improve mental health care infrastructure, the ongoing impact of colonization perpetuates biomedical responses to mental health. Kenya ratified the UN Convention on the Rights of Persons with Disabilities (CRPD) in 2008 though mental health, criminal, and civil laws continue to be in violation of the Convention. We take a human rights and equity lens to critically analyze the biomedical dominance in mental health policy and practice. We employ an intersectional analytic framework to contextualize experiences of mental health injustices and apply aspects of an Intersectionality Based Policy Analysis Framework to the Ministry of Health’s Kenya Mental Health Policy 2015-2030 (2015) and the Ministry of East African Community (EAC) Labour and Social Protection’s National Plan of Action on Implementation of Recommendations made by the Committee on the Rights of Persons with Disabilities (2016) to explore how policy discourses influence understandings of mental health and responses. We analyze a disjuncture between human rights and social determinants framings of mental health in policy, and how a default to western biomedical solutions for addressing mental distress dominate institutionally and in practice. We urge the Kenyan government to abolish coercive mental health practices, remove systemic barriers that hinder participation, and establish supports to empower people with psychosocial disabilities and their organizational representatives (USP-Kenya) to ensure mental health responses are consistent with international human rights treaties.

Background: Managing children with cerebral palsy (CP) in poorly-resourced contexts, especially those with greater functional limitations, is challenging. Unmitigated orthopaedic complications can further restrict already compromised functional capacity. Where rehabilitation skills and knowledge are scarce, primary healthcare worker- and caregiver-implemented routines are warranted. The essential elements of a home-based routine to mitigate musculoskeletal (MSK) complications in children with severe CP in resource-limited settings (RLSs) have not been determined. Objectives: To summarise the evidence for programmes and interventions that mitigate MSK complications in children with severe CP and make recommendations for a programme suited to RLSs. Method: Scientific databases and professional websites were searched for studies and reports describing guidelines, interventions or programmes for children aged 0–18 years with severe, partially- or non-ambulant CP, that included aims for the prevention of MSK complications. Articles reporting on surgical, pharmacological and advanced or expensive technological interventions were excluded. Results: A total of 57 studies or reports were included in the review. Low-grade evidence exists for 24-hour postural management (24-h PM), supported standing, sustained stretching and splinting to mitigate MSK complications in children with CP. Caregiver training and support, and integration of the programme into daily routines were identified as important components for successful implementation. Conclusion: Clinical guidelines and evidence that support caregiver-delivered interventions to reduce MSK complications in children with severe CP are limited, and only weak recommendations can be made. Clinical implications: There is a need for context-specific, home-based intervention programmes to prevent MSK complications in children with CP in RLSs.

Extreme cold in February 2021 precipitated prolonged power failure in Texas. In Houston, many patients presented for carbon monoxide exposure from neighborhoods with lower per capita income, higher rates of limited English proficiency, and greater median Social Vulnerability Indices than Greater Houston. Weather-related disasters disproportionately affect socially vulnerable communities.

Trauma induced coagulopathy (TIC) describes a complex set of coagulation changes affecting severely injured patients. The thrombomodulin-protein C axis is believed to be central to the evolution of TIC. Soluble thrombomodulin (sTM) levels are elevated after injury. Our objectives were to explore whether sTM (at concentrations found in patients after injury) plays an important role in TIC, and specifically to evaluate the effect of sTM and activated protein C (APC) on thrombin generation (TG) and clot lysis time (CLT). Plasma from healthy volunteers was spiked with rising concentrations of sTM and APC and the effects on TG and CLT were analysed. Plasma samples from a cohort of trauma patients were evaluated using TG and CLT, and results correlated to clinical parameters and FVIII, FV, APC, sTM and fibrinolytic measures. Increasing sTM concentrations in volunteer plasma led to reductions in ETP and prolongation of 50% CLT times, in a dose dependent manner. No effect on TG or CLT was seen with rising APC concentrations. In 91 trauma patients, higher sTM values were associated with greater, rather than reduced, ETP (median 1483 vs. 1681 nM/min) and longer 50% CLT times (41.9 vs. 54.0 mins). In conclusion, sTM concentrations, across trauma ranges, impact both TG and 50% CLT times, unlike APC. Despite increased circulating sTM levels, the overriding dynamic coagulation effects seen after injury are: (a) accelerated thrombin generation and (b) increased rates of fibrinolysis. We find no evidence for sTM as the major determinant of the coagulation changes seen in early TIC.

Arthroscopic anterior cruciate ligament (ACL) reconstruction has been the gold standard of care for ACL injuries for many years. Recently, there has been growing literature and interest in arthroscopic primary ACL repair in select patients with predominantly proximally based ACL tears. This Technical Note demonstrates a surgical technique that offers an efficient minimally invasive and physeal-sparing anatomic ACL repair with all-inside internal brace augmentation that in the short term has offered good results for our patients.

OBJECTIVES: The purpose of this literature review is to analyze the current body of literature regarding the use of microneedling with a therapeutic agent, to encourage tissue regeneration and gingival health in the periodontium. METHODS: The database used for this literature review was Google Scholar with Augusta University Library accessible articles. The keywords used to find these articles were micro-needling, tissue regeneration, periodontal tissue attachment, guided tissue regeneration, and therapeutic agents. The mesh terms used were needles, periodontitis, tissues, regeneration, and epithelial attachment with the word “AND” between. Articles that were older than five years were filtered out, leaving 428 articles. Then irrelevant articles were manually filtered out. Six articles were then selected, with one of the articles being a literature review used for background information. RESULTS: Each article reviewed showed how micro-needling with therapeutic adjuncts can have a positive effect on the gingiva. These effects range from increased interdental papilla height, increased gingival thickness and collagen formation, decreased inflammation, and decreased severity of the destruction of the periodontal tissues. Micro-needling initiates a natural wound-healing process in the gingiva, and with the help of different therapeutic agents, positive results can be observed. CONCLUSIONS: Each of the articles selected used a different agent and a different micro-needling procedure. The patient's needs and wants are determining factors in which therapeutic agent would be used to assist the micro-needling procedure. Future research is needed to compare additives and procedures, in addition to micro-needling. More long-term studies are necessary to determine the lasting effects on the periodontium and overall health of the patient. In conclusion, micro-needling seems to be a cost-effective, non-invasive treatment with noticeable improvement for tissue regeneration and gingival health, proving to show validity and worth in becoming an accepted practice and treatment option in dentistry. IMPLICATIONS: Micro-needling with a therapeutic adjunct is an efficient way for dental practices to incorporate a minimally invasive treatment into a wide variety of different treatment regimens.

Background: Little is known regarding the characteristics, treatment patterns, and outcomes in patients with adult congenital heart disease (ACHD) admitted to cardiac intensive care units (CICUs). Objectives: The authors sought to better define the contemporary epidemiology, treatment patterns, and outcomes of ACHD admissions in the CICU. Methods: The Critical Care Cardiology Trials Network is a multicenter network of CICUs in North America. Participating centers contributed prospective data from consecutive admissions during 2-month annual snapshots from 2017 to 2022. We analyzed characteristics and outcomes of admissions with ACHD compared with those without ACHD. Multivariable logistic regression was used to assess mortality in ACHD vs non-ACHD admissions. Results: Of 23,299 CICU admissions across 42 sites, there were 441 (1.9%) ACHD admissions. Shunt lesions were most common (46.1%), followed by right-sided lesions (29.5%) and complex lesions (28.7%). ACHD admissions were younger (median age 46 vs 67 years) than non-ACHD admissions. ACHD admissions were more commonly for heart failure (21.3% vs 15.7%, P

IntroductionDeletion or mutation of members of the spectrin gene family contributes to many neurologic and neuropsychiatric disorders. While each spectrinopathy may generate distinct neuropathology, the study of βΙ spectrin’s role (Sptb) in the brain has been hampered by the hematologic consequences of its loss.MethodsJaundiced mice (ja/ja) that lack βΙ spectrin suffer a rapidly fatal hemolytic anemia. We have used exchange transfusion of newborn ja/ja mice to blunt their hemolytic pathology, enabling an examination of βΙ spectrin deficiency in the mature mouse brain by ultrastructural and biochemical analysis.ResultsβΙ spectrin is widely utilized throughout the brain as the βΙΣ2 isoform; it appears by postnatal day 8, and concentrates in the CA1,3 region of the hippocampus, dentate gyrus, cerebellar granule layer, cortical layer 2, medial habenula, and ventral thalamus. It is present in a subset of dendrites and absent in white matter. Without βΙ spectrin there is a 20% reduction in postsynaptic density size in the granule layer of the cerebellum, a selective loss of ankyrinR in cerebellar granule neurons, and a reduction in the level of the postsynaptic adhesion molecule NCAM. While we find no substitution of another spectrin for βΙ at dendrites or synapses, there is curiously enhanced βΙV spectrin expression in the ja/ja brain.DiscussionβΙΣ2 spectrin appears to be essential for refining postsynaptic structures through interactions with ankyrinR and NCAM. We speculate that it may play additional roles yet to be discovered.

Simian immunodeficiency virus (SIV) vaccines based upon 68-1 Rhesus Cytomegalovirus (RhCMV) vectors show remarkable protection against pathogenic SIVmac239 challenge. Across multiple independent rhesus macaque (RM) challenge studies, nearly 60% of vaccinated RM show early, complete arrest of SIVmac239 replication after effective challenge, whereas the remainder show progressive infection similar to controls. Here, we performed viral sequencing to determine whether the failure to control viral replication in non-protected RMs is associated with the acquisition of viral escape mutations. While low level viral mutations accumulated in all animals by 28 days-post-challenge, which is after the establishment of viral control in protected animals, the dominant circulating virus in virtually all unprotected RMs was nearly identical to the challenge stock, and there was no difference in mutation patterns between this cohort and unvaccinated controls. These data definitively demonstrate that viral mutation does not explain lack of viral control in RMs not protected by RhCMV/SIV vaccination. We further demonstrate that during chronic infection RhCMV/SIV vaccinated RMs do not acquire escape mutation in epitopes targeted by RhCMV/SIV, but instead display mutation in canonical MHC-Ia epitopes similar to unvaccinated RMs. This suggests that after the initial failure of viral control, unconventional T cell responses induced by 68-1 RhCMV/SIV vaccination do not exert strong selective pressure on systemically replicating SIV.

Summary: Background: We evaluated the association of hepatitis B virus (HBV) treatment with all-cause, and liver-related mortality among individuals with HBV and cirrhosis in British Columbia (BC), Canada. Methods: This analysis included people diagnosed with HBV and had cirrhosis in the BC Hepatitis Testers Cohort, including data on all individuals diagnosed with HBV from 1990 to 2015 in BC and integrated with healthcare administrative data. We followed people with cirrhosis from the first cirrhosis diagnosis date until death or December 31, 2020. We compared all-cause and liver related mortality between those who received treatment and those who did not. HBV treatment was considered a time-varying variable. We performed multivariable Cox proportional hazards model and competing risk regression models to assess the association of HBV treatment with all causes, and liver-related mortality respectively using inverse probability of treatment weighted population. Findings: Among 4962 individuals with HBV and cirrhosis, 48.1% received HBV treatment. Treated individuals had a median follow-up of 2.97 years, compared to 2.87 years for untreated individuals. The treated group was older (median age 57 vs 54 years), had higher proportion of treated of males [1802 (75.50%) vs 1766 (68.8%)], from urban area [2318 (97.2%) vs 2355 (91.8%)], and from East and South Asian ethnicity [1506 (63.1%) vs 709 (27.5%)] compared to untreated group. Untreated people experienced higher all-cause mortality (115.47 vs. 35.72 per 1000 person-years) and liver-related mortality (49.86 vs. 11.39 per 1000 person-years). Multivariable models showed that HBV treatment significantly lowered the risk of all-cause mortality (adjusted hazard ratio (aHR) 0.74; 95% CI: 0.65, 0.84) and liver-related mortality (adjusted subdistribution hazard ratio (asHR) 0.72; 95% CI: 0.58, 0.89) compared to untreated individuals. Among untreated individuals with HBV, those with HCV coinfection had a higher risk of both all-cause and liver-related mortality (aHR 1.57; 95% CI: 1.22, 2.04, and asHR 1.60; 95% CI: 1.25, 2.05, respectively). Interpretation: HBV treatment was associated with a significant reduction in all-cause and liver-related mortality among individuals with cirrhosis. The findings highlight the need for treatment among individuals with HBV related cirrhosis especially those with coinfection with hepatitis C virus. Funding: This work was supported by the BC Centre for Disease Control and the Canadian Institutes of Health Research (CIHR) [Grant # NHC-142832, PJT-156066, and SC1 -178736]. JDM has received doctoral fellowship from the Canadian Network on Hepatitis C (CanHepC). DJ has received Doctoral Research Award (#201910DF1-435705-64343) from the Canadian Institutes of Health Research (CIHR) and doctoral fellowship from the CanHepC. CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (CIHR) (NHC-142832) and the Public Health Agency of Canada (PHAC).

Abstract Singlet‐to‐triplet intersystem crossing (ISC) in organic molecules is intimately connected with their geometries: by modifying the molecular shape, symmetry selection rules pertaining to spin‐orbit coupling can be partially relieved, leading to extra matrix elements for increased ISC. As an analog to this molecular design concept, the study finds that the lattice symmetry of supramolecular polymers also defines their triplet formation efficiencies. A supramolecular polymer self‐assembled from weakly interacting molecules is considered. Its 2D oblique unit cell effectively renders it as a coplanar array of 1D molecular columns weakly bound to each other. Using momentum‐resolved photoluminescence imaging in combination with Monte Carlo simulations, the study found that photogenerated charge carriers in the supramolecular polymer predominantly recombine as spin‐uncorrelated carrier pairs through inter‐column charge transfer states. This lattice‐defined recombination pathway leads to a substantial triplet formation efficiency (≈60%) in the supramolecular polymer. These findings suggest that lattice symmetry of micro‐/macroscopic structures relying on intermolecular interactions can be strategized for controlled triplet formation.

IntroductionAlzheimer’s disease and related dementias (ADRD) represent a substantial global public health challenge with multifaceted impacts on individuals, families, and healthcare systems. Brief cognitive screening tools such as the Mini-Cog© can help improve recognition of ADRD in clinical practice, but widespread adoption continues to lag. We compared the Digital Clock and Recall (DCR), a next-generation process-driven adaptation of the Mini-Cog, with the original paper-and-pencil version in a well-characterized clinical trial sample.MethodsDCR was administered to 828 participants in the Bio-Hermes-001 clinical trial (age median ± SD = 72 ± 6.7, IQR = 11; 58% female) independently classified as cognitively unimpaired (n = 364) or as having mild cognitive impairment (MCI, n = 274) or dementia likely due to AD (DLAD, n = 190). MCI and DLAD cohorts were combined into a single impaired group for analysis. Two experienced neuropsychologists rated verbal recall accuracy and digitally drawn clocks using the original Mini-Cog scoring rules. Inter-rater reliability of Mini-Cog scores was computed for a subset of the data (n = 508) and concordance between Mini-Cog rule-based and DCR scoring was calculated.ResultsInter-rater reliability of Mini-Cog scoring was good to excellent, but Rater 2’s scores were significantly higher than Rater 1’s due to variation in clock scores (p

Background: Progressive respiratory muscle weakness and ineffective cough contribute to morbidity and mortality in children with neuromuscular disorders (NMD). Inspiratory muscle training (IMT) aims to preserve or improve respiratory muscle strength and reduce respiratory morbidity. This study aimed to determine the safety and efficacy of IMT in children with NMD. Methods/design: A randomised cross-over study compared a 3-month intervention (IMT) with control periods (no IMT). Children diagnosed with NMD (5 years – 18 years) performed 30 breaths (at 30% of maximum inspiratory mouth pressure [Pimax]) with an electronic threshold device, twice daily. During the control period, participants did not perform any IMT. Discussion: Twenty three children (median [interquartile range {IQR}] age of 12.33 [10.03–14.17] years), mostly male (n = 20) and non-ambulant (n = 14) participated. No adverse events related to IMT were reported. No difference in median patient hospitalisation and respiratory tract infection (RTI) rates between non-training and intervention periods (p = 0.60; p = 0.21) was found. During IMT, Pimax and peak cough flow improved with a mean ± standard deviation (s.d.) of 14.57 ± 15.67 cmH2O and 32.27 ± 36.60 L/min, compared to 3.04 ± 11.93 cmH2O (p = 0.01) and −16.59 ± 48.29 L/min (p = 0.0005) during the non-training period. Similar to other studies, spirometry did not show a significant change. Conclusion: A 3-month IMT programme in children with NMD appears safe and well-tolerated, with significant improvement in respiratory muscle strength and cough efficacy. Clinical implications: Inspiratory muscle training could be considered a cost-effective adjunct to respiratory management in children with NMD. Trial Registration: Pan African Clinical Trial Registry, PACTR201506001171421, https://pactr.samrc.ac.za.

Abstract Earth is now experiencing declines in insect abundance and diversity unparalleled in human history. The drivers underlying those declines are many, complex, and incompletely known. Here, using a natural experiment, we report the first test of the hypothesis that forest defoliation by an invasive outbreak insect compromises the fitness of a native insect via damage‐induced increases in toxicity of the forest canopy. We demonstrate that defoliation by the invasive spongy moth (Lymantria dispar) elicits an average 8.4‐fold increase in foliar defense expression among aspen (Populus tremuloides) genotypes. In turn, elevated defense dramatically reduces survivorship, feeding, and growth of a charismatic mega moth (Anthereae polyphemus). This work suggests that changes to the phytochemical landscape of forests, mediated by invasive outbreak insects, are likely to negatively impact native insects, with potential repercussions for community diversity and ecosystem function across expansive scales.

To survive, animals must convert sensory information into appropriate behaviours1,2. Vision is a common sense for locating ethologically relevant stimuli and guiding motor responses3-5. How circuitry converts object location in retinal coordinates to movement direction in body coordinates remains largely unknown. Here we show through behaviour, physiology, anatomy and connectomics in Drosophila that visuomotor transformation occurs by conversion of topographic maps formed by the dendrites of feature-detecting visual projection neurons (VPNs)6,7 into synaptic weight gradients of VPN outputs onto central brain neurons. We demonstrate how this gradient motif transforms the anteroposterior location of a visual looming stimulus into the fly's directional escape. Specifically, we discover that two neurons postsynaptic to a looming-responsive VPN type promote opposite takeoff directions. Opposite synaptic weight gradients onto these neurons from looming VPNs in different visual field regions convert localized looming threats into correctly oriented escapes. For a second looming-responsive VPN type, we demonstrate graded responses along the dorsoventral axis. We show that this synaptic gradient motif generalizes across all 20 primary VPN cell types and most often arises without VPN axon topography. Synaptic gradients may thus be a general mechanism for conveying spatial features of sensory information into directed motor outputs.

BACKGROUND: Systemic sclerosis (SSc) is a rare, complex, connective tissue disorder. Interstitial lung disease (ILD) is common in SSc, occurring in 35-52% of patients and accounting for 20-40% of mortality. Evolution of therapeutic options has resulted in a lack of consensus on how to manage this condition. This Delphi study was initiated to develop consensus recommendations based on expert physician insights regarding screening, progression, treatment criteria, monitoring of response, and the role of recent therapeutic advances with antifibrotics and immunosuppressants in patients with SSc-ILD. METHODS: A modified Delphi process was completed by pulmonologists (n = 13) and rheumatologists (n = 12) with expertise in the management of patients with SSc-ILD. Panelists rated their agreement with each statement on a Likert scale from - 5 (complete disagreement) to + 5 (complete agreement). Consensus was predefined as a mean Likert scale score of ≤  - 2.5 or ≥  + 2.5 with a standard deviation not crossing zero. RESULTS: Panelists recommended that all patients with SSc be screened for ILD by chest auscultation, spirometry with diffusing capacity of the lungs for carbon monoxide, high-resolution computed tomography (HRCT), and/or autoantibody testing. Treatment decisions were influenced by baseline and changes in pulmonary function tests, extent of ILD on HRCT, duration and degree of dyspnea, presence of pulmonary hypertension, and potential contribution of reflux. Treatment success was defined as stabilization or improvement of signs or symptoms of ILD and functional status. Mycophenolate mofetil was identified as the initial treatment of choice. Experts considered nintedanib a therapeutic option in patients with progressive fibrotic ILD despite immunosuppressive therapy or patients contraindicated/unable to tolerate immunotherapy. Concomitant use of nintedanib with MMF/cyclophosphamide can be considered in patients with advanced disease at initial presentation, aggressive ILD, or significant disease progression. Although limited consensus was achieved on the use of tocilizumab, the experts considered it a therapeutic option for patients with early SSc and ILD with elevated acute-phase reactants. CONCLUSIONS: This modified Delphi study generated consensus recommendations for management of patients with SSc-ILD in a real-world setting. Findings from this study provide a management algorithm that will be helpful for treating patients with SSc-ILD and addresses a significant unmet need.

A large body of work has linked neural oscillations in the alpha-band (8-13 Hz) to visual perceptual outcomes. In particular, studies have found that alpha phase prior to stimulus onset predicts stimulus detection, and sensory responses and that the frequency of alpha can predict temporal properties of perception. These findings have bolstered the idea that alpha-band oscillations reflect rhythmic sampling of visual information, however the mechanisms of this are unclear. Recently two contrasting hypotheses have been proposed. According to the rhythmic perception account, alpha oscillations impose phasic inhibition on perceptual processing and primarily modulate the amplitude or strength of visual responses and thus the likelihood of stimulus detection. On the other hand, the discrete perception account proposes that alpha activity discretizes perceptual inputs thereby reorganizing the timing (not only the strength) of perceptual and neural processes. In this paper, we sought neural evidence for the discrete perception account by assessing the correlation between individual alpha frequencies (IAF) and the latency of early visual evoked event-related potential (ERP) components. If alpha cycles were responsible for shifting neural events in time, then we may expect higher alpha frequencies to be associated with earlier afferent visual ERPs. Participants viewed large checkerboard stimuli presented to either the upper or lower visual field that were designed to elicit a large C1 ERP response (thought to index feedforward primary visual cortex activation). We found no reliable correlation between IAF and the C1 latency, or subsequent ERP component latencies, suggesting that the timing of these visual-evoked potentials was not modulated by alpha frequency. Our results thus fail to find evidence for discrete perception at the level of early visual responses but leave open the possibility of rhythmic perception.

Animals raised in environments that prevent natural foraging opportunities may have difficulty adapting to novelty, such as feeding and management changes. Our objective was to evaluate how early provision and presentation of forage in dairy calves affected response to novel TMR (total mixed ration; grain and alfalfa) at weaning. Holstein heifer calves were housed individually in a covered outdoor hutch with an attached uncovered wire-fenced pen on sand bedding. Calves were fed a diet of starter grain and milk replacer (5.7-8.4L/d step-up) via a bottle (Control, n = 9) or given additional access to mountaingrass hay presented either in a bucket (Bucket, n = 9), or PVC pipe feeder (Pipe, n = 9). Treatments were applied from birth through 50 d of age, when step-down weaning began. All calves had 3 buckets and a pipe feeder provided in their uncovered pen area. On d 50, each calf was briefly blocked inside their hutch. TMR was put in the 3rd bucket that previously contained hay (Bucket) or was empty (Control, Pipe). The calf was released from the hutch and video-recorded for 30 min. Neophobia towards TMR was affected by prior experience with presentation: Bucket calves began eating TMR faster than Pipe and Control (P≤0.012) and showed the fewest number of startle responses (P = 0.004). Intake was similar across groups (P = 0.978), suggesting this apparent neophobia was transient, but Control calves took longer to eat than Bucket (P

BackgroundChronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are characterized by shared exposures and clinical features, but distinct genetic and pathologic features exist. These features have not been well-studied using large-scale gene expression datasets. We hypothesized that there are divergent gene, pathway, and cellular signatures between COPD and IPF.MethodsWe performed RNA-sequencing on lung tissues from individuals with IPF (n = 231) and COPD (n = 377) compared to control (n = 267), defined as individuals with normal spirometry. We grouped the overlapping differential expression gene sets based on direction of expression and examined the resultant sets for genes of interest, pathway enrichment, and cell composition. Using gene set variation analysis, we validated the overlap group gene sets in independent COPD and IPF data sets.ResultsWe found 5010 genes differentially expressed between COPD and control, and 11,454 genes differentially expressed between IPF and control (1% false discovery rate). 3846 genes overlapped between IPF and COPD. Several pathways were enriched for genes upregulated in COPD and downregulated in IPF; however, no pathways were enriched for genes downregulated in COPD and upregulated in IPF. There were many myeloid cell genes with increased expression in COPD but decreased in IPF. We found that the genes upregulated in COPD but downregulated in IPF were associated with lower lung function in the independent validation cohorts.ConclusionsWe identified a divergent gene expression signature between COPD and IPF, with increased expression in COPD and decreased in IPF. This signature is associated with worse lung function in both COPD and IPF.

Decarbonization of the industrial heat demand through electrification could contribute significantly to climate change mitigation efforts. In the US industry, thermal processes accounted for 75% of the total final energy demand in 2018, of which 17% is consumed by conventional industrial boilers (excluding cogeneration) for steam generation. Electric boilers have a small share in the US industrial steam generation due to several techno-economic reasons. This study employs a bottom-up approach to investigate the sector-level and state-level techno-enviro-economic potentials of deploying electric boilers in the US industry in different timeframes. The results show that the technical potential energy and CO2 savings by electrifying industrial boilers are 595 PJ and 200 MtCO2 per year in 2050, respectively; however, these incur additional costs in each sector. Although there may be individual cost-effective opportunities for electrifying boilers in specific industrial sites, the overall costs are high in all industrial sectors and states due to the large disparity between electricity and combustion fuel prices. To overcome the highlighted techno-economic barriers, a comprehensive action plan for different stakeholders is also formulated. This study provides novel insights that should inform policymakers’ and executives’ decisions about the electrification of the current and future US industrial boiler systems.

Background Access to care for children with kidney disease is limited in less well-resourced regions of the world and paediatric nephrology (PN) workforce development with good practical skills is critical. Methods Retrospective review of a PN training program and trainee feedback from 1999 to 2021, based at Red Cross War Memorial Children's Hospital (RCWMCH), University of Cape Town. Results A regionally appropriate 1-2-year training program enrolled 38 fellows with an initial 100% return rate to their country of origin. Program funding included fellowships from the International Pediatric Nephrology Association (IPNA), International Society of Nephrology (ISN), International Society of Peritoneal Dialysis (ISPD), and the African Paediatric Fellowship Program (APFP). Fellows were trained on both in- and out-patient management of infants and children with kidney disorders. 'Hands-on skills' training included examination, diagnosis and management skills, practical insertion of peritoneal dialysis catheters for management of acute kidney injury and kidney biopsies. Of 16 trainees who completed > 1 year of training, 14 (88%) successfully completed subspecialty exams and 9 (56%) completed a master's degree with a research component. PN fellows reported that their training was appropriate and enabled them to make a difference in their respective communities. Conclusions This training program has successfully equipped African physicians with the requisite knowledge and skills to provide PN services in resource-constrained areas for children with kidney disease. The provision of funding from multiple organizations committed to paediatric kidney disease has contributed to the success of the program, along with the fellows' commitment to build PN healthcare capacity in Africa. Graphical abstract, Author(s): Mignon I. McCulloch [sup.1] , Andrew C. Argent [sup.2] , Brenda Morrow [sup.2] , Peter Nourse [sup.1] , Ashton Coetzee [sup.1] , Christel Du Buisson [sup.3] , Deveshni Reddy [...]

Abstract Objective With potential therapies for many forms of Charcot‐Marie‐Tooth disease (CMT), responsive outcome measures are urgently needed for clinical trials. Quantitative lower limb MRI demonstrated progressive calf intramuscular fat accumulation in the commonest form, CMT1A with large responsiveness. In this study, we evaluated the responsiveness and validity in the three other common forms, due to variants in GJB1 (CMTX1), MPZ (CMT1B) and MFN2 (CMT2A). Methods 22 CMTX1, 21 CMT1B and 21 CMT2A patients and matched controls were assessed at a 1‐year interval. Intramuscular fat fraction (FF) was evaluated using three‐point Dixon MRI at thigh and calf level along with clinical measures including CMT examination score, clinical strength assessment, CMT‐HI and plasma neurofilament light chain. Results All patient groups had elevated muscle fat fraction at thigh and calf levels, with highest thigh FF and atrophy in CMT2A. There was moderate correlation between calf muscle FF and clinical measures (CMTESv2 rho = 0.405; p = 0.001, ankle MRC strength rho = −0.481; p