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In response to biodiversity loss and biotic community homogenization in urbanized landscapes, there are increasing efforts to conserve and increase biodiversity within urban areas. Accordingly, around the world, previously extirpated species are (re)colonizing and otherwise infiltrating urban landscapes, while other species are disappearing from these landscapes. Tracking the occurrence of traditionally urban intolerant species and loss of traditionally urban tolerant species should be a management goal of urban areas, but we generally lack tools to study this phenomenon. To address this gap, we first used species occurrences from iNaturalist, a large collaborative dataset of species observations, to calculate an urban association index (UAI) for 967 native animal species that occur in the city of Los Angeles. On average, the occurrence of native species was negatively associated with our composite measure of urban intensity, with the exception of snails and slugs, which instead occur more frequently in areas of increased urban intensity. Next, we assessed 8,348 0.25 x 0.25 mile grids across the City of Los Angeles to determine the average grid-level UAI scores (i.e., a summary of the UAIs present in a grid cell, which we term Community Urban Tolerance Index or CUTI). We found that areas of higher urban intensity host more urban tolerant species, but also that taxonomic groups differ in their aggregate tolerance of urban areas, and that spatial patterns of tolerance vary between groups. The framework established here has been designed to be iteratively reevaluated by city managers of Los Angeles in order to track the progress of initiatives to preserve and encourage urban biodiversity, but can be rescaled to sample different regions within the city or different cities altogether to provide a valuable tool for city managers globally.

This study determined whether initiation of pharmacologic treatment was delayed for newly diagnosed osteoporosis patients during the COVID-19 pandemic. 1,189 patients ≥50 years with newly diagnosed osteoporosis using dual-energy x-ray absorptiometry (DXA) screening at a single academic institution were included. Patients with previous osteoporosis were excluded. Patients diagnosed between March 1, 2018-January 31, 2020 (pre-pandemic cohort, n = 576) were compared to those diagnosed between March 1, 2020-January 31, 2022 (pandemic cohort, n = 613). Age, sex, race, ethnicity, ordering providers (primary vs specialty), and pharmacological agents were evaluated. Primary outcomes included proportion of patients prescribed therapy within 3 and 6-months of diagnosis, and mean time from diagnosis to treatment initiation. The pre-pandemic cohort had more White patients (74.3 vs 68.4%, p = .02) and no differences between remaining demographic variables. Only 40.5% of newly diagnosed patients initiated pharmacologic therapy within 6 months. Patients treated at 3-months (31.8 vs 35.4%, p = 0.19) and 6-months (37.8 vs 42.9, p = 0.08) were comparable between cohorts (47.2 vs 50.2% p = 0.30). Mean time from diagnosis to treatment initiation was similar (46 vs 45 days, p = 0.72). There were no treatment differences based on gender, race, or ethnicity or between ordering providers (65.1 vs 57.4% primary care, p = 0.08). Bisphosphonates were most often prescribed in both cohorts (89% vs 82.1%). This is the first study assessing COVID-19's impact on pharmacologic treatment of newly diagnosed osteoporosis. 40.5% of newly diagnosed patients were treated pharmacologically within six months of diagnosis, and the pandemic did not significantly affect treatment rates.

BackgroundIn recognition of the interconnected nature of complex challenges such as COVID-19, a collaborative, multisectoral, and transdisciplinary approach, referred to as One Health, has been employed to address sustainable development and strengthen global health security. Although significant investments have been made to build global health capacity, characterization of the One Health is absent from the literature.Methods and findingsWe collected and analyzed perspectives from students, graduates, workers, and employers in One Health through a multinational online survey across health disciplines and sectors. Respondents were recruited through professional networks. A total of 828 respondents from 66 countries participated, representing governmental and academic institutions and students, among others; 57% were female, and 56% had completed professional health degrees. Interpersonal communication, communication with non-scientific audiences, and the ability to work in transdisciplinary teams were valued in the workplace and were considered essential competencies to build an interdisciplinary health workforce. Employers indicated difficulty recruiting workers, while workers indicated limited availability of positions. Employers identified limited funding and ill-defined career pathways as prominent challenges for retaining One Health workers.ConclusionsSuccessful One Health workers use interpersonal skills and scientific knowledge to address complex health challenges. Aligning the definition of One Health will likely improve the matching of job seekers and employers. Encouraging the employment of the One Health approach for a diverse range of positions, even if they do not explicitly include "One Health" in the job title, and clarifying the expectations, roles and responsibilities within a transdisciplinary team will lead to building a stronger workforce. As One Health has evolved to address food insecurity, emerging diseases, and antimicrobial resistance, it holds promise for supporting an interdisciplinary global health workforce that can make substantial progress on Sustainable Development Goals and improve global health security for all.

ObjectivesLeft Ventricular Assist Devices (LVADs) for destination therapy (DT) are used in many countries but in some, like the UK, LVADs are not commissioned due to uncertainty around their cost-effectiveness. Existing economic evaluations of LVADs for these patients have limitations. This study aimed to estimate the cost-effectiveness of LVADs as destination therapy, compared to optimal medical therapy, in the UK.MethodsA cost-utility analysis from a UK healthcare perspective was conducted, using a Markov model. The model incorporated the impact of major events and complications. Sub-group analyses considered different severities of heart failure on cost-effectiveness. Uncertainty was measured in deterministic and probabilistic sensitivity analyses.ResultsLVAD produced additional 2.78 (95% CI 2.46-3.14) QALYs at an incremental cost of £152,329 (95% CI £125,665 - £181,812) compared to medical management, giving an incremental cost-effectiveness ratio (ICER) of £54,748 per QALY. The ICER remained above the accepted thresholds of cost-effectiveness in the UK if a small proportion of patients receiving LVAD becomes eligible for a heart transplant and for all subgroups based on heart failure severity. The deterministic sensitivity analysis showed that the ongoing outpatient costs had a significant impact on the results.ConclusionsOur analysis found that LVADs are not cost-effective as destination therapy in the UK if a willingness to pay threshold of £50,000 per QALY gained or disease severity modifiers, were applied. Robust data on ongoing costs for LVAD and medical management are needed.

A striking global health development over the past few decades has been the increasing prevalence of overweight and obesity. At the same time, depression has become increasingly common in almost all high-income countries. We investigated whether body weight, measured by body mass index (BMI), has a causal effect on depression symptoms in Finland. Using data drawn from the Cardiovascular Risk in Young Finns Study (N = 1,523, mean age 41.9, SD 5), we used linear regression to establish the relationship between BMI and depression symptoms measured by 21-item Beck's Depression Inventory. To identify causal relationships, we used the Mendelian randomization (MR) method with weighted sums of genetic markers (single nucleotide polymorphisms, SNPs) as instruments for BMI. We employ instruments (polygenic risk scores, PGSs) with varying number of SNPs that are associated with BMI to evaluate the sensitivity of our results to instrument strength. Based on linear regressions, higher BMI was associated with a higher prevalence of depression symptoms among females (b = 0.238, p = 0.000) and males (b = 0.117, p = 0.019). However, the MR results imply that the positive link applies only to females (b = 0.302, p = 0.007) but not to males (b = -0.070, p = 0.520). Poor instrument strength may explain why many previous studies that have utilized genetic instruments have been unable to identify a statistically significant link between BMI and depression-related traits. Although the number of genetic markers in the instrument had only a minor effect on the point estimates, the standard errors were much smaller when more powerful instruments were employed.

BackgroundAmyotrophic lateral sclerosis (ALS), also known as Lou Gehrig´s disease, is a rare neurological condition and is the most common motor neurone disease. It is a fatal disease with specific loss of motor neurons in the spinal cord, brain stem, and motor cortex leading to progressive paralysis and usually death within five years of diagnosis. There remains no cure for ALS, and management is focused on a combination of neuroprotective medication, respiratory support, and management by multidisciplinary clinics.Patients and methodsThis prospective, single-arm, open-label phase II clinical trial of sustained weekly administration of 2 mg/kg ILB® (a low-molecular weight dextran sulphate) was conducted in a single UK hospital. Eligible patients were at least 18 years and had a definite diagnosis of ALS according to El Escorial Criteria. The co-primary outcomes were safety, tolerability, and quantity of ILB® administered. EudraCT number. 2018-000668-28.FindingsBetween 18-Apr-2019 and 27-Mar-2020, 11 patients were recruited and treated for up to 38 weeks. There were no treatment terminations or withdrawals. One serious adverse event was reported, which was not related to ILB® and resolved without sequalae. 270 mild/moderate adverse events were reported with no intolerable events occurring during the trial. The total number of ILB® treatments administered per patient ranged from 4 to 38, with a cumulative dose ranging from 745 to 6668 mg. As a result of the COVID-19 pandemic and the high-risk status of study participants, recruitment and treatment was suspended early in Mar-2020. At the long-term follow-up, three patients had died after the trial was halted, between 53 and 62 weeks after their final ILB® injection.InterpretationLong-term weekly ILB® injections of 2 mg/kg was well tolerated and had an acceptable safety profile in patients with ALS.Trial registrationEudraCT: 2018-000668-28. clinicaltrials.gov: NCT03705390. This trial adheres to the principles of GCP in the design, conduct, recording and reporting of clinical trials as listed in part 2, "Conditions and Principles which apply to all Clinical Trials" under the header "Principles based on Articles 2 to 5 of the EU GCP Directive" in the Medicines for Human Use Clinical Trials Regulations (as amended in SI 2006/1928). For clarity, the study did not conform to all aspects of the International Conference on Harmonisation (ICH) E6 R2 Guidelines for GCP (also known as 'ICH GCP'). Of note, we did not use an external database, perform 100% source data verification, and only primary outcome data were analysed in parallel by a second, independent statistician.

BackgroundOsteoarthritis (OA) is a leading cause of musculoskeletal pain and disability among Americans. Physical therapy (PT) is recommended per the 2019 ACR /Arthritis Foundation Guideline for Treatment of OA of the Hand, Hip, and Knee. During COVID-19, access to healthcare has been altered in a variety of clinical settings, with the pandemic creating delays in healthcare, with an unknown impact on access to PT care for OA.ObjectivesWe sought to determine whether referrals to PT for OA were reduced in 2020 during the COVID-19 pandemic compared to 2019.MethodsA retrospective analysis was done of 3586 PT referrals placed by the University of California, Davis for 206 OA ICD-10 codes from January to November 2019 and from January to November 2020. The numbers of PT referrals per month of each year were compared using both descriptive statistics and Poisson Regression analysis.ResultsA total of 1972 PT referrals for OA were placed from January to November 2019. Only 1614 referrals for OA were placed from January to November 2020, representing a significant decrease (p = 0.001). Month-by-month analysis of 2020 compared to 2019 revealed statistically significant drops in PT referrals for OA in April (p = 0.001), May (p = 0.001), and August (p = 0.001).ConclusionsThese findings reveal a significant reduction in the number of referrals for PT for OA placed in 2020 during the first year of the COVID-19 pandemic. These reductions were particularly evident in the months following state-mandated actions and closures. Factors associated with this outcome may include decreased access to primary care providers, perceptions of PT availability by health care providers, decreased mobility limiting access to both clinic and PT appointments, and/or willingness to engage in PT by patients during the pandemic.

BackgroundFew cross-sectional studies report iron deficiency (ID) prevalence in women of different race/ethnicity and ages in US or Canada.Materials and methodsWe evaluated screening observations on women who participated between 2001-2003 in a cross-sectional, primary care-based sample of adults ages ≥25 y whose observations were complete: race/ethnicity; age; transferrin saturation; serum ferritin; and HFE p.C282Y and p.H63D alleles. We defined ID using a stringent criterion: combined transferrin saturation

Objectives: Left Ventricular Assist Devices (LVADs) for destination therapy (DT) are used in many countries but in some, like the UK, LVADs are not commissioned due to uncertainty around their cost-effectiveness. Existing economic evaluations of LVADs for these patients have limitations. This study aimed to estimate the cost-effectiveness of LVADs as destination therapy, compared to optimal medical therapy, in the UK. Methods: A cost-utility analysis from a UK healthcare perspective was conducted, using a Markov model. The model incorporated the impact of major events and complications. Sub-group analyses considered different severities of heart failure on cost-effectiveness. Uncertainty was measured in deterministic and probabilistic sensitivity analyses. Results: LVAD produced additional 2.78 (95% CI 2.46–3.14) QALYs at an incremental cost of £152,329 (95% CI £125,665 - £181,812) compared to medical management, giving an incremental cost-effectiveness ratio (ICER) of £54,748 per QALY. The ICER remained above the accepted thresholds of cost-effectiveness in the UK if a small proportion of patients receiving LVAD becomes eligible for a heart transplant and for all subgroups based on heart failure severity. The deterministic sensitivity analysis showed that the ongoing outpatient costs had a significant impact on the results. Conclusions: Our analysis found that LVADs are not cost-effective as destination therapy in the UK if a willingness to pay threshold of £50,000 per QALY gained or disease severity modifiers, were applied. Robust data on ongoing costs for LVAD and medical management are needed. [ABSTRACT FROM AUTHOR]

Sublethal effects of oil spills may dampen seabird rehabilitation success due to lingering negative impacts of contamination and stress on reproduction and long-term survival. These effects can be difficult to measure while birds are in care as well as once birds are released. Expression of sexually selected traits that are sensitive to condition can provide information on physiological status of birds. We evaluated plumage molt and gular pouch skin color of California brown pelicans (Pelecanus occidentalis californicus) following oil contamination and rehabilitation to test for differences between previously oiled and rehabilitated (post-spill) and presumably uncontaminated pelicans. Post-spill pelicans released with either color leg bands alone, or bands plus harness-mounted satellite GPS tags, were relocated and visually assessed in the field at non-breeding communal roosts and compared to surrounding unmarked pelicans in the general population. Non-oiled pelicans bearing GPS tags were also included in the study. Post-spill pelicans lagged the general population in molt of ornamental yellow crown feathers but hind neck transition into white plumage was not significantly different. Both post-spill and non-oiled pelicans wearing GPS tags had lower gular redness scores than the unmarked, non-oiled population. Pre-breeding gular pouch redness of post-spill pelicans was more strongly influenced by wearing of a GPS tag than a history of oil contamination and rehabilitation. Gular pouch redness of post-spill pelicans in the first 18 months after release was positively correlated with long term survivorship. If gular pouch color is a condition-dependent sexual signal and overall health influences plumage molt progression, our results indicate that many post-spill pelicans marked with bands alone were in relatively good condition going into the next breeding season, but those released with electronic tags experienced additional stress due to wearing the equipment, introducing a confounding variable to the post-release study.

Objective To identify individual characteristics associated with outcomes following combined first-line interventions for knee osteoarthritis. Methods MEDLINE, CINAHL, Scopus, Web of Science Core Collection and the Cochrane library were searched. Studies were included if they reported an association between baseline factors and change in pain or function following combined exercise therapy, osteoarthritis education, or weight management interventions for knee osteoarthritis. Risk of bias was assessed using Quality in Prognostic Factor Studies. Data was visualised and a narrative synthesis was conducted for key factors (age, sex, BMI, comorbidity, depression, and imaging severity). Results 32 studies were included. Being female compared to male was associated with 2–3 times the odds of a positive response. Older age was associated with reduced odds of a positive response. The effect size (less than 10% reduction) is unlikely to be clinically relevant. It was difficult to conclude whether BMI, comorbidity, depression and imaging severity were associated with pain and function outcomes following a combined first-line intervention for knee osteoarthritis. Low to very low certainty evidence was found for sex, BMI, depression, comorbidity and imaging severity and moderate certainty evidence for age. Varying study methods contributed to some difficulty in drawing clear conclusions. Conclusions This systematic review found no clear evidence to suggest factors such as age, sex, BMI, OA severity and presence of depression or comorbidities are associated with the response to first-line interventions for knee OA. Current evidence indicates that some groups of people may respond equally to first-line interventions, such as those with or without comorbidities. First-line interventions consisting of exercise therapy, education, and weight loss for people with knee OA should be recommended irrespective of sex, age, obesity, comorbidity, depression and imaging findings.

Acute exacerbations of COPD (AECOPDs) are one of the leading causes of preventable hospital admissions in Australia. Exacerbations are the strongest predictor for future exacerbations. The period immediately following an exacerbation is a high-risk period for recurrence and critical time to intervene. The aim of this study was to identify current general practice care for patients following an AECOPD in Australia and gain insights into knowledge of evidence-based care. A cross-sectional survey was created and disseminated electronically to Australian general practitioners (GPs). Data were analysed descriptively. Comparisons between groups were made using Chi squared tests. From 64 responses, 47% were familiar with the COPD-X Plan. Only 50% described reviewing patients within seven days of discharge mostly related to a lack of awareness of the hospital admission. 50% of surveyed GPs reported hospital discharge summaries did not provide the information they required. Smoking, immunisation and medications were regularly assessed by >90% respondents at follow-up visits, while referrals to pulmonary rehabilitation, and evaluation of spirometry and oxygen therapy were not prioritised. GPs appear to require support to increase their familiarity with COPD guidelines and inform evidence-based clinical practice. The handover/communication process from hospital to primary care appears an important area for future improvement.

BackgroundIn recognition of the interconnected nature of complex challenges such as COVID-19, a collaborative, multisectoral, and transdisciplinary approach, referred to as One Health, has been employed to address sustainable development and strengthen global health security. Although significant investments have been made to build global health capacity, characterization of the One Health is absent from the literature.Methods and findingsWe collected and analyzed perspectives from students, graduates, workers, and employers in One Health through a multinational online survey across health disciplines and sectors. Respondents were recruited through professional networks. A total of 828 respondents from 66 countries participated, representing governmental and academic institutions and students, among others; 57% were female, and 56% had completed professional health degrees. Interpersonal communication, communication with non-scientific audiences, and the ability to work in transdisciplinary teams were valued in the workplace and were considered essential competencies to build an interdisciplinary health workforce. Employers indicated difficulty recruiting workers, while workers indicated limited availability of positions. Employers identified limited funding and ill-defined career pathways as prominent challenges for retaining One Health workers.ConclusionsSuccessful One Health workers use interpersonal skills and scientific knowledge to address complex health challenges. Aligning the definition of One Health will likely improve the matching of job seekers and employers. Encouraging the employment of the One Health approach for a diverse range of positions, even if they do not explicitly include "One Health" in the job title, and clarifying the expectations, roles and responsibilities within a transdisciplinary team will lead to building a stronger workforce. As One Health has evolved to address food insecurity, emerging diseases, and antimicrobial resistance, it holds promise for supporting an interdisciplinary global health workforce that can make substantial progress on Sustainable Development Goals and improve global health security for all.

PurposeThis study determined whether initiation of pharmacologic treatment was delayed for newly diagnosed osteoporosis patients during the COVID-19 pandemic.Methods1,189 patients ≥50 years with newly diagnosed osteoporosis using dual-energy x-ray absorptiometry (DXA) screening at a single academic institution were included. Patients with previous osteoporosis were excluded. Patients diagnosed between March 1, 2018-January 31, 2020 (pre-pandemic cohort, n = 576) were compared to those diagnosed between March 1, 2020-January 31, 2022 (pandemic cohort, n = 613). Age, sex, race, ethnicity, ordering providers (primary vs specialty), and pharmacological agents were evaluated. Primary outcomes included proportion of patients prescribed therapy within 3 and 6-months of diagnosis, and mean time from diagnosis to treatment initiation.ResultsThe pre-pandemic cohort had more White patients (74.3 vs 68.4%, p = .02) and no differences between remaining demographic variables. Only 40.5% of newly diagnosed patients initiated pharmacologic therapy within 6 months. Patients treated at 3-months (31.8 vs 35.4%, p = 0.19) and 6-months (37.8 vs 42.9, p = 0.08) were comparable between cohorts (47.2 vs 50.2% p = 0.30). Mean time from diagnosis to treatment initiation was similar (46 vs 45 days, p = 0.72). There were no treatment differences based on gender, race, or ethnicity or between ordering providers (65.1 vs 57.4% primary care, p = 0.08). Bisphosphonates were most often prescribed in both cohorts (89% vs 82.1%).ConclusionsThis is the first study assessing COVID-19's impact on pharmacologic treatment of newly diagnosed osteoporosis. 40.5% of newly diagnosed patients were treated pharmacologically within six months of diagnosis, and the pandemic did not significantly affect treatment rates.

In a phase I dose escalation and safety study (NCT02555397), a replication-competent oncolytic adenovirus expressing yCD, TK and hIL-12 (Ad5-yCD/mutTKSR39rep-hIL-12) was administered in 15 subjects with localized recurrent prostate cancer (T1c-T2) at increasing doses (1 × 1010, to 1 × 1012 viral particles) followed by 7-day treatment of 5-fluorocytosine (5-FC) and valganciclovir (vGCV). The primary endpoint was toxicity through day 30 while the secondary and exploratory endpoints were quantitation of IL-12, IFNγ, CXCL10 and peripheral blood mononuclear cells (PBMC). The study maximum tolerated dose (MTD) was not reached indicating 1012 viral particles was safe. Total 115 adverse events were observed, most of which (92%) were grade 1/2 that did not require any treatment. Adenoviral DNA was detected only in two patients. Increase in IL-12, IFNγ, and CXCL10 was observed in 57%, 93%, and 79% patients, respectively. Serum cytokines demonstrated viral dose dependency, especially apparent in the highest-dose cohorts. PBMC analysis revealed immune system activation after gene therapy in cohort 5. The PSA doubling time (PSADT) pre and post treatment has a median of 1.55 years vs 1.18 years. This trial confirmed that replication-competent Ad5-IL-12 adenovirus (Ad5-yCD/mutTKSR39rep-hIL-12) was well tolerated when administered locally to prostate tumors.

BackgroundStudies of the lived experience of chronic obstructive pulmonary disease (COPD) reveal a number of challenges patients face when interacting with healthcare providers that may be exacerbated by unwillingness or inability to quit smoking. However, none have explored, in-depth, primary care experiences among patients with COPD in community healthcare settings.Aims/ objectiveThe study investigated healthcare experiences of patients living independently in the community with COPD who smoked or had recently quit (at most within the last 5 years), seeking care in primary care settings.MethodAn Interpretative Phenomenological Analysis (IPA) involving thirteen participants purposively recruited from social media posts in COPD and carer support groups, general community groups, community noticeboards and paid adverts on social media. In-depth interviews were held between February and April 2022 by phone or Zoom™ and explored patient experience of primary care, focusing on how smoking patterns, addiction and stigma impact upon and shape these experiences.ResultsParticipants were aged between 45 to 75 years. Nine were female and two thirds were current smokers. Problematic experiences including time-constrained consultations, having to self-advocate for care "…go digging myself and then go and see him and say, can we do this, can we do that type of thing?" and guilt about smoking were common. Positive care experiences described non-judgemental interpersonal interactions with doctors, timely referral, proactive care and trust "I have an actual great trust for my GP… they're awesome, they'll look after you". Participants described how their care experience shifted as primary care adapted care delivery during COVID-19.ConclusionsPro-active, empathetic care from general practitioners is desired from patients living with COPD. Stigma and fear of judgement was an important underlying driver of negative care experiences contributing to delayed help seeking from general practitioners.

Loneliness is a highly prevalent experience in schizophrenia. Theoretical models developed in the general population propose that loneliness is tantamount to a feeling of being unsafe, is accompanied by enhanced environmental threat perception, and leads to poor physical, emotional, and cognitive functioning. Previous research has reported that loneliness is associated with poorer physical and emotional health in schizophrenia; however, few studies have directly compared loneliness and its correlates in persons with schizophrenia and non-psychiatric comparison subjects. The purpose of the current study was to evaluate similarities and differences in the construct of loneliness, the equivalency of the measurement of this construct, and similarities and differences in the pattern of external correlates of loneliness between schizophrenia and non-psychiatric comparison groups. The third version of the University of California, Los Angeles Loneliness Scale (UCLA-3) was administered to 116 individuals with schizophrenia or schizoaffective disorder and 106 non-psychiatric comparison subjects. Additional clinical and positive psychological measures were collected, as well as demographic characteristics of the two groups. Multiple groups confirmatory factor analysis revealed that the UCLA-3 was best characterized by a bifactor model in which all items loaded on a general loneliness dimension as well as one of two orthogonal method factors reflecting item wording in both groups. Furthermore, the UCLA-3 exhibited invariant measurement of these latent constructs across groups. Mean levels of loneliness were nearly a standard deviation higher in the schizophrenia group. Nonetheless, the overall pattern and strength of correlates were largely similar across groups, with loneliness being positively associated with depression, anxiety, and perceived stress, and negatively correlated with mental well-being, happiness, and resilience. Subtle differences in correlates of age, optimism, and satisfaction with life were found. Overall, loneliness appears to be distinct from other schizophrenia-related deficits and operates similarly across schizophrenia and NC groups, suggesting that theoretical models of loneliness developed in the general population may generalize to schizophrenia.

Background Screening program participants with iron overload (IO) phenotypes without HFE p.C282Y/p.C282Y are incompletely characterized. Methods We studied white participants who had IO phenotypes without p.C282Y/p.C282Y in post-screening clinical examinations (CE). We defined IO phenotypes as a) elevated serum ferritin (SF) and transferrin saturation (TS) at screening and CE, and b) absence of IO treatment, anemia, transfusion >10 units, alcohol intake >30 g/d, hepatitis B or C, and pregnancy. We defined IO-related disease as elevated alanine or aspartate aminotransferase (ALT/AST) or swelling/tenderness of 2nd/3rd metacarpophalangeal (MCP) joints. All participants had HFE p.C282Y and p.H63D genotyping. Results There were 32 men and 26 women (mean age 54±16 y). Median food/supplemental iron intakes were 14.3/0.0 mg/d. Relative risks of HFE genotypes were 12.9 (p.C282Y/p.H63D), 3.0 (p.H63D/p.H63D), 1.9 (p.C282Y/wt), 0.9 (p.H63D/wt), and 0.5 (wt/wt) compared to 42,640 white screening participants without IO phenotypes or p.C282Y/p.C282Y. Regression on SF revealed positive associations: MCV (p = 0.0006; β coefficient = 0.4531); swelling/tenderness of MCP joints (p = 0.0033; β = 0.3455); and p.H63D/wt (p = 0.0015; β = 0.4146). IO-related disease (18 elevated ALT/AST, one swelling/tenderness of MCP joints) occurred in 19 participants (7 men, 12 women). Median MCV was higher in participants with IO-related disease (97 fL vs. 94 fL; p = 0.0007). Logistic regression on IO-related disease revealed a significant association with diabetes (p = 0.0416; odds ratio 18.9 (95% confidence interval 1.0, 341.1)). Conclusions In the present 58 screening program participants who had IO phenotypes without HFE p.C282Y/p.C282Y, relative risks of HFE genotypes p.C282Y/p.H63D, p.H63D/p.H63D, and p.C282Y/wt were significantly higher than in 42,640 white screening participants with neither IO phenotypes nor p.C282Y/p.C282Y. SF was significantly associated with MCV, swelling/tenderness of 2nd/3rd MCP joints, and p.H63D/wt. IO-related disease was significantly associated with MCV and diabetes.

This research presents a framework to enable computer-automated observation and monitoring of bottlenose dolphins (Tursiops truncatus) in a zoo environment. The resulting approach enables detailed persistent monitoring of the animals that is not possible using manual annotation methods. Fixed overhead cameras were used to opportunistically collect ∼100 hours of observations, recorded over multiple days, including time both during and outside of formal training sessions, to demonstrate the viability of the framework. Animal locations were estimated using convolutional neural network (CNN) object detectors and Kalman filter post-processing. The resulting animal tracks were used to quantify habitat use and animal kinematics. Additionally, Kolmogorov-Smirnov analyses of the swimming kinematics were used in high-level behavioral mode classification. The object detectors achieved a minimum Average Precision of 0.76, and the post-processed results yielded 1.24 × 107 estimated dolphin locations. Animal kinematic diversity was found to be lowest in the morning and peaked immediately before noon. Regions of the zoo habitat displaying the highest activity levels correlated to locations associated with animal care specialists, conspecifics, or enrichment. The work presented here demonstrates that CNN object detection is viable for large-scale marine mammal tracking, and results from the proposed framework will enable future research that will offer new insights into dolphin behavior, biomechanics, and how environmental context affects movement and activity.

Background Panton-Valentine Leukocidin (PVL) toxin in Staphylococcus aureus has been associated with both severe pneumonia and skin and soft tissue infections. However, there are only limited data on how this virulence factor may influence the clinical course or complications of bacteremic S. aureus infections. Methods Between September 2016 and March 2018, S. aureus isolates from clinical cultures from hospitals in an academic medical center underwent comprehensive genomic sequencing. Four hundred sixty-nine (29%) of 1681 S. aureus sequenced isolates were identified as containing the genes that encode for PVL. Case patients with one or more positive blood cultures for PVL were randomly matched with control patients having positive blood cultures with lukF/lukS-PV negative (PVL strains from a retrospective chart review). Results 51 case and 56 control patients were analyzed. Case patients were more likely to have a history of injection drug use, while controls more likely to undergo hemodialysis. Isolates from 78.4% of case patients were methicillin resistant as compared to 28.6% from control patients. Case patients had a higher incidence of pneumonia and skin and soft tissue infection and longer duration of fever without differences in length of bacteremia. Clinical cure or expiration was comparable. Conclusions These results are consistent with prior observations associating the PVL toxin with both community-acquired MRSA strains as well as severe staphylococcal pneumonia. The presence of the PVL toxin does not appear to otherwise influence the natural history of bacteremic S. aureus disease other than in prolonging the duration of fever.

Introduction Over recent decades, the abundance and geographic ranges of wild ungulate species have expanded in many parts of Europe, including the UK. Populations are managed to mitigate their ecological impacts using interventions, such as shooting, fencing and administering contraception. Predicting how target species will respond to interventions is critical for developing sustainable, effective and efficient management strategies. However, the quantity and quality of evidence of the effects of interventions on ungulate species is unclear. To address this, we systematically mapped research on the effects of population management on wild ungulate species resident in the UK. Methods We searched four bibliographic databases, Google Scholar and nine organisational websites using search terms tested with a library of 30 relevant articles. Worldwide published peer-reviewed articles were considered, supplemented by ‘grey’ literature from UK-based sources. Three reviewers identified and screened articles for eligibility at title, abstract and full-text levels, based on predefined criteria. Data and metadata were extracted and summarised in a narrative synthesis supported by structured graphical matrices. Results A total of 123 articles were included in the systematic map. Lethal interventions were better represented (85%, n = 105) than non-lethal interventions (25%, n = 25). Outcomes related to demography and behaviour were reported in 95% of articles (n = 117), whereas effects on health, physiology and morphology were studied in only 11% of articles (n = 14). Well-studied species included wild pigs (n = 58), red deer (n = 28) and roe deer (n = 23). Conclusions Evidence for the effects of population management on wild ungulate species is growing but currently limited and unevenly distributed across intervention types, outcomes and species. Priorities for primary research include: species responses to non-lethal interventions, the side-effects of shooting and studies on sika deer and Chinese muntjac. Shooting is the only intervention for which sufficient evidence exists for systematic review or meta-analysis.

BackgroundA subgroup of patients with Major Depressive Disorder shows signs of low-grade inflammation and metabolic abberances, while antidepressants can induce weight gain and subsequent metabolic disorders, and lacking antidepressant response is associated with inflammation.ObjectivesA comprehensive investigation of patient phenotypes and their predictive capability for weight gain and treatment response after psychotropic treatment will be performed. The following factors will be analyzed: inflammatory and metabolic markers, gut microbiome composition, lifestyle indicators (eating behavior, physical activity, chronotype, patient characteristics (childhood adversity among others), and polygenic risk scores.MethodsPsychiatric inpatients with at least moderate Major Depressive Disorder will be enrolled in a prospective, observational, naturalistic, monocentric study using stratified sampling. Ethical approval was obtained. Primary outcomes at 4 weeks will be percent weight change and symptom score change on the Montgomery Asberg Depression Rating Scale. Both outcomes will also be binarized into clinically relevant outcomes at 5% weight gain and 50% symptom score reduction. Predictors for weight gain and treatment response will be tested using multiple hierachical regression for continuous outcomes, and multiple binary logistic regression for binarized outcomes. Psychotropic premedication, current medication, eating behavior, baseline BMI, age, and sex will be included as covariates. Further, a comprehensive analysis will be carried out using machine learning. Polygenic risk scores will be added in a second step to estimate the additional variance explained by genetic markers. Sample size calculation yielded a total amount of N = 171 subjects.DiscussionPatient and physician expectancies regarding the primary outcomes and non-random sampling may affect internal validity and external validity, respectively. Through the prospective and naturalistic design, results will gain relevance to clinical practice. Examining the predictive value of patient profiles for weight gain and treatment response during pharmacotherapy will allow for targeted adjustments before and concomitantly to the start of treatment.

BackgroundTo identify 30-day rehospitalizations in patients discharged with heart failure (HF) based on clinical indications, physiologic measures and symptoms.MethodsFifty-six patients with heart failure participated. After discharge to home, clinical indicators of dyspnea, fatigue, orthopnea, dyspnea with exertion, daily weight, edema, heart rate, blood pressure, mental condition, medication adherence, and overall well-being were reported by participants daily for up to 30 days.ResultsJoint modeling of longitudinal and time-to-event approach was applied to assess the association of readmission with longitudinal measurements. There was no association between demographic, physiological, or laboratory variables and re-hospitalization within 30 days post discharge. Perceptions of dyspnea (p = .012) and feeling unwell (p < .001) were associated with rehospitalization. Patients struggling to breath were 10.7 times more likely to be readmitted than those not struggling to breath.ConclusionPerceived measures, particularly dyspnea and feeling unwell were more important factors than demographic, physiological, or laboratory parameters in predicting 30-day rehospitalizations in this racially diverse cohort. The symptomatic experience of heart failure is an important indicator of rehospitalization.

Dissolved black carbon (DBC) is the condensed aromatic portion of dissolved organic matter produced from the incomplete combustion of biomass and other thermogenic processes. DBC quantification facilitates the examination of the production, accumulation, cycling, transformation, and effects of biologically recalcitrant condensed aromatic carbon in aquatic environments. Due to the heterogeneous nature of DBC molecules, concentrations are difficult to measure directly. Here, the method for DBC quantification consists of oxidizing condensed aromatic carbon to benzenepolycarboxylic acids (BPCAs), which are used as proxies for the assessment of DBC in the original sample. The concentrations of oxidation products (BPCAs) are quantified using high-performance liquid chromatography. DBC concentrations are determined from the concentration of BPCAs using a previously established conversion factor. Details and full descriptions of the preparative and analytical procedures and techniques of the BPCA method are usually omitted for brevity in published method sections and method-specific papers. With this step-by-step protocol, we aim to clarify the steps of DBC analysis, especially for those adopting or conducting the BPCA method for the first time.

BackgroundIndividuals with respiratory conditions, such as asthma, are particularly susceptible to adverse health effects associated with higher levels of ambient air pollution and temperature. This study evaluates whether hourly levels of fine particulate matter (PM2.5) and dry bulb globe temperature (DBGT) are associated with the lung function of adult participants with asthma.Methods and findingsGlobal positioning system (GPS) location, respiratory function (measured as forced expiratory volume at 1 second (FEV1)), and self-reports of asthma medication usage and symptoms were collected as part of the Exposure, Location, and Lung Function (ELF) study. Hourly ambient PM2.5 and DBGT exposures were estimated by integrating air quality and temperature public records with time-activity patterns using GPS coordinates for each participant (n = 35). The relationships between acute PM2.5, DBGT, rescue bronchodilator use, and lung function collected in one week periods and over two seasons (summer/winter) were analyzed by multivariate regression, using different exposure time frames. In separate models, increasing levels in PM2.5, but not DBGT, were associated with rescue bronchodilator use. Conversely DBGT, but not PM2.5, had a significant association with FEV1. When DBGT and PM2.5 exposures were placed in the same model, the strongest association between cumulative PM2.5 exposures and the use of rescue bronchodilator was identified at the 0-24 hours (OR = 1.030; 95% CI = 1.012-1.049; p-value = 0.001) and 0-48 hours (OR = 1.030; 95% CI = 1.013-1.057; p-value = 0.001) prior to lung function measure. Conversely, DBGT exposure at 0 hours (β = 3.257; SE = 0.879; p-value>0.001) and 0-6 hours (β = 2.885; SE = 0.903; p-value = 0.001) hours before a reading were associated with FEV1. No significant interactions between DBGT and PM2.5 were observed for rescue bronchodilator use or FEV1.ConclusionsShort-term increases in PM2.5 were associated with increased rescue bronchodilator use, while DBGT was associated with higher lung function (i.e. FEV1). Further studies are needed to continue to elucidate the mechanisms of acute exposure to PM2.5 and DBGT on lung function in asthmatics.

Biologging tags are a key enabling tool for investigating cetacean behavior and locomotion in their natural habitat. Identifying and then parameterizing gait from movement sensor data is critical for these investigations, but how best to characterize gait from tag data remains an open question. Further, the location and orientation of a tag on an animal in the field are variable and can change multiple times during a deployment. As a result, the relative orientation of the tag with respect to (wrt) the animal must be determined for analysis. Currently, custom scripts that involve species-specific heuristics tend to be used in the literature. These methods require a level of knowledge and experience that can affect the reliability and repeatability of the analysis. Swimming gait is composed of a sequence of body poses that have a specific spatial pattern, and tag-based measurements of this pattern can be utilized to determine the relative orientation of the tag. This work presents an automated data processing pipeline (and software) that takes advantage of these patterns to 1) Identify relative motion between the tag and animal; 2) Estimate the relative orientation of the tag wrt the animal using a data-driven approach; and 3) Calculate gait parameters that are stable and invariant to animal pose. Validation results from bottlenose dolphin tag data show that the average relative orientation error (tag wrt the body) after processing was within 11 degrees in roll, pitch, and yaw directions. The average precision and recall for detecting instances of relative motion in the dolphin data were 0.87 and 0.89, respectively. Tag data from humpback and beluga whales were then used to demonstrate how the gait analysis can be used to enhance tag-based investigations of movement and behavior. The MATLAB source code and data presented in the paper are publicly available (https://github.com/ding-z/cetacean-pose-gait-analysis.git), along with suggested best practices.

Remdesivir (RDV) is the only antiviral drug approved for COVID-19 therapy by the FDA. Another drug LAGEVRIO™ (molnupiravir) though has not been approved yet by FDA but has been authorized on December 23, 2021, for emergency use to treat adults with mild-to moderate COVID-19 symptoms and for whom alternative COVID-19 treatment options are not clinically appropriate. The fact is that the efficacy of RDV is, however, limited in vivo though it is highly promising in vitro against SARS-CoV-2 virus. In this paper we are focusing on the action mechanism of RDV and how it can be improved in vivo. The stability of RDV alone and on encapsulation with our platform technology based polymer NV-387 (NV-CoV-2), were compared in presence of plasma in vitro and in vivo. Furthermore, a non-clinical pharmacology study of NV-CoV-2 (Polymer) and NV CoV-2 (Polymer encapsulated Remdesivir) in both NL-63 infected and uninfected rats was done. In addition, the antiviral activity of NV-CoV-2 and NV-CoV-2-R was compared with RDV in a cell culture study. The results are (i) NV-CoV-2 polymer encapsulation protects RDV from plasma-mediated catabolism in both in vitro and in vivo, studies; (ii) Body weight measurements of the normal (uninfected) rats after administration of the test materials (NV-CoV-2 and NV-CoV-2-R) showed no toxic effects. (iii) Body weight measurements and survival rates of the NL-63 infected rats were similar to the uninfected rats after treatment with NV-CoV-2 and NV-CoV-2-R. Overall, the efficacy as an antiviral regimens were found in this order as below; NV-CoV-2-R > NV-CoV-2 > RDV. Our platform technology based NV-387-encapsulated-RDV (NV-CoV-2-R) drug has a dual effect against different variants of the coronaviruses. First, NV-CoV-2 is an antiviral regimen. Secondly, RDV is protected from plasma-mediated degradation in transit. All together, NV-CoV-2-R is the safest and efficient regimen against COVID-19.

BackgroundIn hemochromatosis, causes of abdominal pain and its associations with cirrhosis are poorly understood.MethodsWe retrospectively compared characteristics of referred hemochromatosis probands with HFE p.C282Y homozygosity with/without biopsy-proven cirrhosis: sex, age, diabetes, heavy alcohol consumption, abdominal pain/tenderness, hepatomegaly, splenomegaly, non-alcoholic fatty liver disease, chronic viral hepatitis, ascites, transferrin saturation (TS), serum ferritin (SF), and iron removed by phlebotomy (QFe). We performed logistic regression on cirrhosis using characteristics identified in univariate comparisons. We performed computerized and manual searches to identify hemochromatosis case series and compiled prevalence data on cirrhosis and abdominal pain and causes of abdominal pain.ResultsOf 219 probands, 57.1% were men. Mean age was 48±13 y. In 22 probands with cirrhosis, proportions of men, mean age, prevalences of heavy alcohol consumption, abdominal pain, abdominal tenderness, hepatomegaly, splenomegaly, and chronic viral hepatitis, and median TS, SF, and QFe were significantly greater than in probands without cirrhosis. Regression analysis revealed three associations with cirrhosis: abdominal pain (p = 0.0292; odds ratio 9.8 (95% CI: 1.2, 76.9)); chronic viral hepatitis (p = 0.0153; 11.5 (95% CI: 1.6, 83.3)); and QFe (p = 0.0009; 1.2 (95% CI: 1.1, 1.3)). Of eight probands with abdominal pain, five had cirrhosis and four had diabetes. One proband each with abdominal pain had heavy alcohol consumption, chronic viral hepatitis B, hepatic sarcoidosis, hepatocellular carcinoma, and chronic cholecystitis, cholelithiasis, and sigmoid diverticulitis. Abdominal pain was alleviated after phlebotomy alone in four probands. In 12 previous reports (1935-2011), there was a negative correlation of cirrhosis prevalence and publication year (p = 0.0033). In 11 previous reports (1935-1996), a positive association of abdominal pain prevalence and publication year was not significant (p = 0.0802).ConclusionsAbdominal pain, chronic viral hepatitis, and QFe are significantly associated with cirrhosis in referred hemochromatosis probands with HFE p.C282Y homozygosity. Iron-related and non-iron-related factors contribute to the occurrence of abdominal pain.

Background: Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig´s disease, is a rare neurological condition and is the most common motor neurone disease. It is a fatal disease with specific loss of motor neurons in the spinal cord, brain stem, and motor cortex leading to progressive paralysis and usually death within five years of diagnosis. There remains no cure for ALS, and management is focused on a combination of neuroprotective medication, respiratory support, and management by multidisciplinary clinics. Patients and methods: This prospective, single-arm, open-label phase II clinical trial of sustained weekly administration of 2 mg/kg ILB® (a low-molecular weight dextran sulphate) was conducted in a single UK hospital. Eligible patients were at least 18 years and had a definite diagnosis of ALS according to El Escorial Criteria. The co-primary outcomes were safety, tolerability, and quantity of ILB® administered. EudraCT number. 2018-000668-28 Findings: Between 18-Apr-2019 and 27-Mar-2020, 11 patients were recruited and treated for up to 38 weeks. There were no treatment terminations or withdrawals. One serious adverse event was reported, which was not related to ILB® and resolved without sequalae. 270 mild/moderate adverse events were reported with no intolerable events occurring during the trial. The total number of ILB® treatments administered per patient ranged from 4 to 38, with a cumulative dose ranging from 745 to 6668 mg. As a result of the COVID-19 pandemic and the high-risk status of study participants, recruitment and treatment was suspended early in Mar-2020. At the long-term follow-up, three patients had died after the trial was halted, between 53 and 62 weeks after their final ILB® injection. Interpretation: Long-term weekly ILB® injections of 2 mg/kg was well tolerated and had an acceptable safety profile in patients with ALS. Trial registration: EudraCT: 2018-000668-28. clinicaltrials.gov: NCT03705390. This trial adheres to the principles of GCP in the design, conduct, recording and reporting of clinical trials as listed in part 2, "Conditions and Principles which apply to all Clinical Trials" under the header "Principles based on Articles 2 to 5 of the EU GCP Directive" in the Medicines for Human Use Clinical Trials Regulations (as amended in SI 2006/1928). For clarity, the study did not conform to all aspects of the International Conference on Harmonisation (ICH) E6 R2 Guidelines for GCP (also known as 'ICH GCP'). Of note, we did not use an external database, perform 100% source data verification, and only primary outcome data were analysed in parallel by a second, independent statistician. [ABSTRACT FROM AUTHOR]

BackgroundAdults with IgG subclass deficiency (IgGSD) with subnormal IgG2 are inadequately characterized.MethodsWe retrospectively analyzed observations in unrelated adults with IgGSD evaluated in a single hematology clinic (1991-2019) and selected those with subnormal serum IgG2 (ResultsThere were 18 patients (94.4% women) with subnormal IgG2. Mean age was 52 ± 11 y. Upper/lower respiratory infection occurred in 94.4%/74.8%, respectively. Autoimmune condition(s), atopy, other allergy, and frequent or severe respiratory infection in first-degree relatives occurred in 44.4%, 44.4%, 61.1%, and 22.2%, respectively. Median IgG2 was 105 mg/dL (83, 116). Subnormal IgG, IgG1, IgG3, IgG4, IgA, and IgM was observed in 66.7%, 50.0%, 100.0%, 5.6%, 33.3%, and 0%, respectively. Lymphocyte subpopulations were normal in most patients. HLA frequencies were similar in patients and controls. Three of 4 patients had no protective S. pneumoniae serotype-specific IgG levels before or after PPSV23. These 18 patients represent 7.6% of 236 adults with IgGSD. Prevalence of subnormal IgG, subnormal IgG3, and subnormal IgA was significantly greater in 18 adults with subnormal IgG2 than 218 adults without subnormal IgG2. Prevalence of subnormal IgM was significantly lower in patients with subnormal IgG2.ConclusionsCharacteristics of adults with IgGSD with subnormal IgG2 include female predominance, other immunologic abnormalities, subnormal IgG3 and/or IgG1, lack of HLA-A and -B association, and suboptimal PPSV23 response.

We describe a new single-streamline based approach to analyse diffusivity within chronic MS lesions. We used the proposed method to examine diffusivity profiles in 30 patients with relapsing multiple sclerosis and observed a significant increase of both RD and AD within the lesion core (0.38+/-0.09 μm2/ms and 0.30+/-0.12 μm2/ms respectively, p

Rickettsioses are neglected and emerging potentially fatal febrile diseases that are caused by obligate intracellular bacteria, rickettsiae. Rickettsia (R.) typhi and R. prowazekii constitute the typhus group (TG) of rickettsiae and are the causative agents of endemic and epidemic typhus, respectively. We recently generated a monoclonal antibody (BNI52) against R. typhi. Characterization of BNI52 revealed that it specifically recognizes TG rickettsiae but not the members of the spotted fever group (SFG) rickettsiae. We further show that BNI52 binds to protein fragments of ±30 kDa that are exposed on the bacterial surface and also present in the periplasmic space. These protein fragments apparently derive from the cytosolic GroEL protein of R. typhi and are also recognized by antibodies in the sera from patients and infected mice. Furthermore, BNI52 opsonizes the bacteria for the uptake by antigen presenting cells (APC), indicating a contribution of GroEL-specific antibodies to protective immunity. Finally, it is interesting that the GroEL protein belongs to 32 proteins that are differentially downregulated by R. typhi after passage through immunodeficient BALB/c CB17 SCID mice. This could be a hint that the rickettsia GroEL protein may have immunomodulatory properties as shown for the homologous protein from several other bacteria, too. Overall, the results of this study provide evidence that GroEL represents an immunodominant antigen of TG rickettsiae that is recognized by the humoral immune response against these pathogens and that may be interesting as a vaccine candidate. Apart from that, the BNI52 antibody represents a new tool for specific detection of TG rickettsiae in various diagnostic and experimental setups.

Background Osteoarthritis (OA) is a leading cause of musculoskeletal pain and disability among Americans. Physical therapy (PT) is recommended per the 2019 ACR /Arthritis Foundation Guideline for Treatment of OA of the Hand, Hip, and Knee. During COVID-19, access to healthcare has been altered in a variety of clinical settings, with the pandemic creating delays in healthcare, with an unknown impact on access to PT care for OA. Objectives We sought to determine whether referrals to PT for OA were reduced in 2020 during the COVID-19 pandemic compared to 2019. Methods A retrospective analysis was done of 3586 PT referrals placed by the University of California, Davis for 206 OA ICD-10 codes from January to November 2019 and from January to November 2020. The numbers of PT referrals per month of each year were compared using both descriptive statistics and Poisson Regression analysis. Results A total of 1972 PT referrals for OA were placed from January to November 2019. Only 1614 referrals for OA were placed from January to November 2020, representing a significant decrease (p = 0.001). Month-by-month analysis of 2020 compared to 2019 revealed statistically significant drops in PT referrals for OA in April (p = 0.001), May (p = 0.001), and August (p = 0.001). Conclusions These findings reveal a significant reduction in the number of referrals for PT for OA placed in 2020 during the first year of the COVID-19 pandemic. These reductions were particularly evident in the months following state-mandated actions and closures. Factors associated with this outcome may include decreased access to primary care providers, perceptions of PT availability by health care providers, decreased mobility limiting access to both clinic and PT appointments, and/or willingness to engage in PT by patients during the pandemic.

Parkinson's disease (PD) is a progressive neurological disorder of the central nervous system that deteriorates motor functions, while it is also accompanied by a large diversity of non-motor symptoms such as cognitive impairment and mood changes, hallucinations, and sleep disturbance. Parkinsonism is evaluated during clinical examinations and appropriate medical treatments are directed towards alleviating symptoms. Tri-axial accelerometers, gyroscopes, and magnetometers could be adopted to support clinicians in the decision-making process by objectively quantifying the patient's condition. In this context, at-home data collections aim to capture motor function during daily living and unobstructedly assess the patients' status and the disease's symptoms for prolonged time periods. This review aims to collate existing literature on PD monitoring using inertial sensors while it focuses on papers with at least one free-living data capture unsupervised either directly or via videotapes. Twenty-four papers were selected at the end of the process: fourteen investigated gait impairments, eight of which focused on walking, three on turning, two on falls, and one on physical activity; ten articles on the other hand examined symptoms, including bradykinesia, tremor, dyskinesia, and motor state fluctuations in the on/off phenomenon. In summary, inertial sensors are capable of gathering data over a long period of time and have the potential to facilitate the monitoring of people with Parkinson's, providing relevant information about their motor status. Concerning gait impairments, kinematic parameters (such as duration of gait cycle, step length, and velocity) were typically used to discern PD from healthy subjects, whereas for symptoms' assessment, researchers were capable of achieving accuracies of over 90% in a free-living environment. Further investigations should be focused on the development of ad-hoc hardware and software capable of providing real-time feedback to clinicians and patients. In addition, features such as the wearability of the system and user comfort, set-up process, and instructions for use, need to be strongly considered in the development of wearable sensors for PD monitoring.

There is an upsurge in the use of mobile phones among higher education students in Ghana, which may result in the nomophobia prevalence with the students. Therefore, the need to assess the influence of nomophobia within the student population in Ghana. This descriptive cross-sectional study investigated the prevalence of nomophobia and the sociodemographic variables, and the association with academic achievement of the understudied population. A self-reporting nomophobia questionnaire, composed of 20 dimensions, was answered by 670 university students to measure the nomophobia prevalence. Raw data were estimated using descriptive statistics, and one-way ANOVA and Independent T-test. While the findings showed diverse grades of nomophobia, statistical significance between academic achievement and the level of nomophobia was observed. This study concludes that there is a high nomophobia prevalence among university students in Ghana as the use of smartphones increases. However, follow-up studies should be conducted in Ghanaian universities to monitor nomophobia and its associates in order to reduce the adverse effects of habitual use of smartphones.

Background China is vulnerable to zoonotic disease transmission due to a large agricultural work force, sizable domestic livestock population, and a highly biodiverse ecology. To better address this threat, representatives from the human, animal, and environmental health sectors in China held a One Health Zoonotic Disease Prioritization (OHZDP) workshop in May 2019 to develop a list of priority zoonotic diseases for multisectoral, One Health collaboration. Methods Representatives used the OHZDP Process, developed by the US Centers for Disease Control and Prevention (US CDC), to prioritize zoonotic diseases for China. Representatives defined the criteria used for prioritization and determined questions and weights for each individual criterion. A review of English and Chinese literature was conducted prior to the workshop to collect disease specific information on prevalence, morbidity, mortality, and Disability-Adjusted Life Years (DALYs) from China and the Western Pacific Region for zoonotic diseases considered for prioritization. Results Thirty zoonotic diseases were evaluated for prioritization. Criteria selected included: 1) disease hazard/severity (case fatality rate) in humans, 2) epidemic scale and intensity (in humans and animals) in China, 3) economic impact, 4) prevention and control, and 5) social impact. Disease specific information was obtained from 792 articles (637 in English and 155 in Chinese) and subject matter experts for the prioritization process. Following discussion of the OHZDP Tool output among disease experts, five priority zoonotic diseases were identified for China: avian influenza, echinococcosis, rabies, plague, and brucellosis. Conclusion Representatives agreed on a list of five priority zoonotic diseases that can serve as a foundation to strengthen One Health collaboration for disease prevention and control in China; this list was developed prior to the emergence of SARS-CoV-2 and the COVID-19 pandemic. Next steps focused on establishing a multisectoral, One Health coordination mechanism, improving multisectoral linkages in laboratory testing and surveillance platforms, creating multisectoral preparedness and response plans, and increasing workforce capacity.

Here we report the complete genome sequence of Teredinibacter turnerae T7901. T. turnerae is a marine gamma proteobacterium that occurs as an intracellular endosymbiont in the gills of wood-boring marine bivalves of the family Teredinidae (shipworms). This species is the sole cultivated member of an endosymbiotic consortium thought to provide the host with enzymes, including cellulases and nitrogenase, critical for digestion of wood and supplementation of the host's nitrogen-deficient diet. T. turnerae is closely related to the free-living marine polysaccharide degrading bacterium Saccharophagus degradans str. 2-40 and to as yet uncultivated endosymbionts with which it coexists in shipworm cells. Like S. degradans, the T. turnerae genome encodes a large number of enzymes predicted to be involved in complex polysaccharide degradation (>100). However, unlike S. degradans, which degrades a broad spectrum (>10 classes) of complex plant, fungal and algal polysaccharides, T. turnerae primarily encodes enzymes associated with deconstruction of terrestrial woody plant material. Also unlike S. degradans and many other eubacteria, T. turnerae dedicates a large proportion of its genome to genes predicted to function in secondary metabolism. Despite its intracellular niche, the T. turnerae genome lacks many features associated with obligate intracellular existence (e.g. reduced genome size, reduced %G+C, loss of genes of core metabolism) and displays evidence of adaptations common to free-living bacteria (e.g. defense against bacteriophage infection). These results suggest that T. turnerae is likely a facultative intracellular ensosymbiont whose niche presently includes, or recently included, free-living existence. As such, the T. turnerae genome provides insights into the range of genomic adaptations associated with intracellular endosymbiosis as well as enzymatic mechanisms relevant to the recycling of plant materials in marine environments and the production of cellulose-derived biofuels.

Many adults with IgG subclass deficiency (IgGSD) experience long intervals of frequent/severe respiratory tract infection before IgGSD diagnosis, but reasons for delays in IgGSD diagnoses are incompletely understood. We performed a retrospective study of 300 white adults (ages ≥18 y) with IgGSD including frequency analyses of age at IgGSD diagnosis, duration of frequent/severe respiratory tract infection before IgGSD diagnosis, and age at onset of frequent/severe infection (calculated). We performed multivariable regressions on age at diagnosis, infection duration, and age at infection onset using these variables, as appropriate: sex; age at diagnosis; diabetes; autoimmune condition(s); atopy; allergy; corticosteroid use; body mass index; serum immunoglobulin isotype levels; blood lymphocyte subsets; three IgGSD-associated human leukocyte antigen-A and -B haplotypes; and referring physician specialties. Mean age at diagnosis was 50 ± 12 (standard deviation) y (median 50 y (range 19-79)). There were 247 women (82.3%). Mean infection duration at IgGSD diagnosis was 12 ± 13 y (median 7 y (range 1-66)). Mean age at infection onset was 38 ± 16 y (median 38 y (range 4, 76)). Age at infection onset was ≥18 y in 95.7% of subjects. Regressions on age at diagnosis and infection duration revealed no significant associations. Regression on age at infection onset revealed one positive association: age at diagnosis (p

BackgroundThere are variations in recommendations from different guidelines regarding the indications for repeat lumbar puncture (LP) in young infants with the diagnosis of bacterial meningitis.ObjectiveTo evaluate the frequency of repeat LPs and the characteristics of cerebrospinal fluid (CSF) parameters in repeated sampling and their predictive values for adverse outcomes in a national cohort.MethodsThis cohort study included infants born January 1, 2013 through December 31, 2014, who had proven or suspected bacterial meningitis within the first 90 days of life at seven paediatric tertiary care hospitals across Canada, and who underwent a repeat LP at the discretion of the treating physicians.ResultsForty-nine of 111 infants (44%) underwent repeat LP at a median of 5 (IQR: 3, 13) days after the LP that led to the diagnosis of bacterial meningitis. Those who had meningitis caused by gram negative bacilli were more likely to have repeat LP than those with gram positive bacteria (77% versus 57%; p = 0.012). White blood cell (WBC) count on the second spinal tap yielded an area under the curve of 0.88 for predicting sequelae of meningitis at discharge from the hospital, with a cut-off value of 366 × 106/L, providing a sensitivity of 91% and specificity of 88%.ConclusionIn this multi-centre retrospective cohort study, infants with gram negative meningitis were more likely to have repeated LP. A high WBC on the second CSF sample was predictive of adverse outcome at the time of discharge from the hospital.

Urban biodiversity offers important benefits to residents and may be crucial to reaching global biodiversity conservation targets, but little research has been conducted on how cities actually plan for biodiversity. In this study, we conducted a mixed methods content analysis of biodiversity plans by 39 cities around the world to determine whether they measured their actions, how they did so (via quantitative indicators and qualitative outputs), and what topics these actions and measures covered. We based our analytical framework on the Singapore Index on Cities' Biodiversity (also known as the City Biodiversity Index), a widely applied 23-indicator index that helps cities track their progress in biodiversity planning. The Singapore Index groups its indicators into the following three core components: native biodiversity, ecosystem services, and governance and management. For actions and measures not classifiable by the Singapore Index, we inductively derived additional categories. Across all plans, we identified 2,231 actions, 346 indicators, and 444 outputs. We found that all of the plans included actions, while 82% included measures (67% included indicators and 72% included outputs). Only 29% of actions were associated with a measure. Overall, the plans covered all of the categories in the Singapore Index, particularly within the core components of native biodiversity and governance and management, though some plans had a narrower focus. The 20 additional urban biodiversity topics that were not covered by the Singapore Index framework included socioeconomic considerations, data collection, genetic diversity, urban agriculture and forestry, green infrastructure, human-wildlife conflicts, indigenous concerns, and citizen science. Indicators were the most common measures for native biodiversity and ecosystem service topics, while outputs were the most common measures for governance and management. Our results may inform the revision and development of urban biodiversity indicators in the post-2020 framework and of other initiatives that guide cities in contributing to local and global biodiversity goals.

The active cervical range of motion (aROM) is assessed by clinicians to inform their decision-making. Even with the ability of neck motion to discriminate injured from non-injured subjects, the mechanisms to explain recovery or persistence of WAD remain unclear. There are few studies of ROM examinations with precision tools using kinematics as predictive factors of recovery rate. The present paper will evaluate the performance of an artificial neural network (ANN) using kinematic variables to predict the overall change of aROM after a period of rehabilitation in WAD patients. To achieve this goal the neck kinematics of a cohort of 1082 WAD patients (55.1% females), with mean age 37.68 (SD 12.88) years old, from across Spain were used. Prediction variables were the kinematics recorded by the EBI® 5 in routine biomechanical assessments of these patients. These include normalized ROM, speed to peak and ROM coefficient of variation. The improvement of aROM was represented by the Neck Functional Holistic Analysis Score (NFHAS). A supervised multi-layer feed-forward ANN was created to predict the change in NFHAS. The selected architecture of the ANN showed a mean squared error of 308.07-272.75 confidence interval for a 95% in the Monte Carlo cross validation. The performance of the ANN was tested with a subsample of patients not used in the training. This comparison resulted in a medium correlation with R = 0.5. The trained neural network to predict the expected difference in NFHAS between baseline and follow up showed modest results. While the overall performance is moderately correlated, the error of this prediction is still too large to use the method in clinical practice. The addition of other clinically relevant factors could further improve prediction performance.

IntroductionAs total health and dental care expenditures in the United States continue to rise, healthcare disparities for low to middle-income Americans creates an imperative to analyze existing expenditures. This study examined health and dental care expenditures in the United States from 1996 to 2016 and explored trends in spending across various population subgroups.MethodsUsing data collected by the Medical Expenditure Panel Survey, this study examined health and dental care expenditures in the United States from 1996 to 2016. Trends in spending were displayed graphically and spending across subgroups examined. All expenditures were adjusted for inflation or deflation to the 2016 dollar.ResultsBoth total health and dental expenditures increased between 1996 and 2016 with total healthcare expenditures increasing from $838.33 billion in 1996 to $1.62 trillion in 2016, a 1.9-fold increase. Despite an overall increase, total expenditures slowed between 2004 and 2012 with the exception of the older adult population. Over the study period, expenditures increased across all groups with the greatest increases seen in older adult health and dental care. The per capita geriatric dental care expenditure increased 59% while the per capita geriatric healthcare expenditure increased 50% across the two decades. For the overall US population, the per capita dental care expenditure increased 27% while the per capita healthcare expenditure increased 60% over the two decades. All groups except the uninsured experienced increased dental care expenditure over the study period.ConclusionsHealthcare spending is not inherently bad since it brings benefits while exacting costs. Our findings indicate that while there were increases in both health and dental care expenditures from 1996 to 2016, these increases were non-uniform both across population subgroups and time. Further research to understand these trends in detail will be helpful to develop strategies to address health and dental care disparities and to maximize resource utilization.