What factors influence physical activity participation in people with rheumatoid arthritis?

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by periods of inflammation and remission. Physical activity can reduce disease activity and lower the risks of associated co-morbidities such as cardiovascular disease. Despite the benefits, a high percentage of people with RA do not participate in regular physical activity.Objective: The purpose of this qualitative literature review was to explore and synthesize the experiences of people with RA to develop better insight of the factors that influence physical activity participation.Method: A systematic search was conducted across five online databases; MEDLINE, CINAHL, ScienceDirect, PsycINFO, Web of Science. Studies were assessed for quality, data were extracted and analyzed using thematic synthesis.Results: A total of 186 articles were identified and screened against inclusion/exclusion criteria. Seven studies met the criteria and were included in this review. Five key themes were identified as the most significant factors to physical activity participation: professional knowledge and guidance; part of a community; knowing me, knowing RA; what’s in it for me; and where, when, how much? Professional knowledge and guidance was the underpinning factor influencing physical activity participation.Conclusion: The results identify several internal and external factors that affect physical activity participation. To engage, facilitate and motivate patients to participate in physical activity, ongoing education and support from health care professionals is required. This will promote better symptom management and maintain functional independence. Additionally, health care professionals need to consider individual preferences and abilities when recommending physical activity

Thin ice, deep snow and surface flooding in Kotzebue Sound: landfast ice mass balance during two anomalously warm winters and implications for marine mammals and subsistence hunting

The inaugural data from the first systematic program of sea ice observations in Kotzebue Sound, Alaska, in 2018 coincided with the first winter in living memory when the Sound was not choked with ice. The following winter of 2018-19 was even warmer and characterized by even less ice. Here we discuss the mass balance of landfast ice near Kotzebue (Qikiktagruk) during these two anomalously warm winters. We use in-situ observations and a 1-D thermodynamic model to address three research questions developed in partnership with an Indigenous Advisory Council. In doing so, we improve our understanding of connections between landfast ice mass balance, marine mammals, and subsistence hunting. Specifically, we show: i) Ice growth stopped unusually early due to strong vertical ocean heat flux, which also likely contributed to early start to bearded seal hunting; ii) Unusually thin ice contributed to widespread surface flooding. The associated snow ice formation partly offset the reduced ice growth, but the flooding likely had a negative impact on ringed seal habitat; iii) Sea ice near Kotzebue during the winters of 2017-18 and 2018-19 was likely the thinnest since at least 1945, driven by a combination of warm air temperatures and a persistent ocean heat flux.

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

A discovery study of daunorubicin induced cardiotoxicity in a sample of acute myeloid leukemia patients prioritizes P450 oxidoreductase polymorphisms as potential risk factor.

Anthracyclines are very effective chemotherapeutic agents; however, their use is hampered by the treatment-induced cardiotoxicity. Genetic variants that help define patient’s sensitivity to anthracyclines will greatly improve the design of optimal chemotherapeutic regimens. However, identification of such variants is hampered by the lack of analytical approaches that address the complex, multi-genic character of anthracycline induced cardiotoxicity. Here, using a multi-SNP based approach, we examined 60 genes coding for proteins involved in drug metabolism and efflux and identified the P450 oxidoreductase (POR) gene to be most strongly associated with daunorubicin induced cardiotoxicity in a population of acute myeloid leukemia patients (FDR adjusted p-value of 0.15). In this sample of cancer patients, variation in the POR gene is estimated to account for some 11.6% of the variability in the drop of left ventricular ejection fraction after daunorubicin treatment, compared to the estimated 13.2% accounted for by the cumulative dose and ethnicity. In post-hoc analysis, this association was driven by 3 SNPs – the rs2868177, rs13240755, and rs4732513 – through their linear interaction with cumulative daunorubicin dose. The unadjusted odds ratios (ORs) and confidence intervals (CIs) for rs2868177 and rs13240755 were estimated to be 1.89 (95% CI: 0.7435 - 4.819; p=0.1756) and 3.18 (95% CI: 1.223 - 8.27; p=0.01376), respectively. Although the contribution of POR variants is expected to be overestimated due to the multiple testing performed in this small pilot study, given that cumulative anthracycline dose is virtually the only factor used clinically to predict the risk of cardiotoxicity, the contribution that genetic analyses of POR can make to the assessment of this risk is worthy of follow up in future investigations

Co-production of knowledge reveals loss of Indigenous hunting opportunities in the face of accelerating Arctic climate change

Profound sea ice loss is rapidly transforming coupled social-ecological Arctic marine systems. However, explicit impacts to harvesting of traditional resources for coastal Indigenous communities remain largely unquantified, particularly where the primary research questions are posed by the Indigenous community as a result of emerging approaches such as knowledge co-production. Here, we directly link reduced sea ice coverage to decreasing harvesting opportunities for ugruk (bearded seal, Erignathus barbatus) as a component of a partnership among a multidisciplinary team of scientists, Indigenous Elder Advisory Council, and sovereign Indigenous Tribe in northwest Alaska. We collaboratively established research questions, coordinated data collection, and interpreted results to understand the causes and consequences of changing ugruk harvests for the community of Qikiqtaġruk (Kotzebue). The duration of spring ugruk hunts by the Qikiqtaġruŋmiut declined significantly during 2003-2019 due to a shift (~3 weeks earlier) in the timing of regional sea ice breakup. Harvests now cease ~26 days earlier than in the past decade. Using historical sea ice records, we further demonstrate that ice coverage in May now resembles conditions that were common in July during the mid-20th century. Overall, we show that climate change is constraining hunting opportunities for this traditional marine resource, although Qikiqtaġruŋmiut hunters have so far been able to offset a shortened season with changes in effort. Notwithstanding recent hunting success in unprecedentedly sparse ice conditions, accessibility to traditional resources remains a prominent concern for many Arctic communities. Management and policy decisions related to Arctic marine mammal resources, such as ugruk, are therefore also interwoven with food security, well-being, and culture of Indigenous communities. Hence, research that originates with Indigenous sovereignty over the entire research process, such as demonstrated here, has the potential to also lead to more inclusive, sustainable, and equitable outcomes in the face of rapid and accelerating Arctic change

The Winter Heat Budget of Sea Ice in Kotzebue Sound: Residual Ocean Heat and the Seasonal Roles of River Outflow

The winters of 2017/18 and 2018/19 saw unprecedented sea ice minima in the Bering and Chukchi Seas. Kotzebue Sound, located in the southeastern corner of the Chukchi Sea, remained largely ice-free throughout the winter in a stark departure from both recorded history and Indigenous oral history. The only sea ice that persisted throughout the winter was landfast ice and most of this occupied a small corner of the Sound near the outflow of the Noatak and Kobuk Rivers. We present oceanographic and atmospheric time series from a heavily instrumented “ice-tethered observatory” located on this landfast ice above the river outflow channel. This observing station was deployed as part of the Ikaaġvik Sikukun (Iñupiaq for “Ice Bridges”) project, in which hypotheses and subsequent observational programs were co-produced in partnership with an Indigenous Elder advisory council in Kotzebue. The measurements allow us to quantify the heat budget of the ice above the outflow channel, and identify the ocean as the primary source of heat contributing to thinning of the ice, which began in early February and accelerated rapidly before recovery of the station in April of 2019. In concert with the ice-tethered observations, we use two years of oceanographic measurements from the mouth of Kotzebue Sound to characterize the influence of river outflow on the heat budget of the landfast ice, revealing a seasonal pattern in which the rivers promote ice formation and growth in the fall/winter, but help to drive melting of the ice in spring and early summer

Characteristics of ringed seal Pusa hispida (‘natchiq’) denning habitat in Kotzebue Sound, Alaska, during a year of limited sea ice and snow

Sea ice and snow are essential to Arctic ecosystems, playing key roles in the lives of Arctic marine mammals and the Indigenous Peoples who rely on them. Ringed seals Pusa hispida (‘natchiq’ in Iñupiaq) use snow-covered dens on sea ice for pupping, but quantitative information on denning habitat requirements is limited, and it is unknown how changes in snow depth and sea-ice extent will impact ringed seals. Here, an Indigenous Elder Advisory used knowledge co-production to quantify fine-scale ringed seal habitat selection patterns in Kotzebue Sound, Alaska (USA), during a year of unprecedentedly limited snow and sea-ice availability. Together, we conducted unoccupied aerial vehicle-based surveys during spring 2019 and related seal counts to survey date, bathymetry, and novel proxies for snow depth and surface roughness that we derived from Landsat 8 surface reflectance and validated with on-ice measurements. Generalized additive models showed that counts of seal groups (all age classes) and pups were associated with later survey dates, deeper water, and habitat with bright Landsat 8 pixel values and intermediate pixel variability, which in turn were correlated with deep snow and surface roughness. We observed shallow snow depths, early sea-ice breakup, and high seal densities consistent with the extreme lack of ice available in 2019. Indigenous Knowledge, intentionally woven with scientific data, provided novel and more nuanced understandings of snow and sea-ice conditions for seals. Our results may give a glimpse at future ringed seal habitat and selection in a warming Arctic

An Evaluation of Neurocognitive Status and Markers of Immune Activation as Predictors of Time to Death in Advanced HIV Infection

Background: Several markers of immune activation have been identified as potential prognostic markers for human immunodeficiency virus (HIV)–associated morbidity and mortality, but the results from studies are conflicting. Objective: To evaluate whether neurocognitive status and baseline levels of plasma and cerebrospinal fluid tumor necrosis factor α (TNF-α), macrophage chemoattractant protein 1 (MCP-1), matrix metalloproteinase 2 (MMP-2), or macrophage colony-stimulating factor (M-CSF) are associated with time to death in a cohort with advanced HIV infection. Design: Cohort study. Setting: Enrollees in the Northeast AIDS Dementia Study. Participants: Three hundred twenty-nine subjects who were positive for HIV-1 and had a CD4 cell count of less than 200/μL (or <300/μL but with cognitive impairment at baseline) were assessed for CD4 cell count, neurocognitive status, pertinent demographic and clinical variables, and plasma and cerebrospinal fluid HIV RNA, TNF-α, MCP-1, MMP-2, and M-CSF levels. Main Outcome Measures: Cox proportional hazards regression models were used to examine the associations between the variables of interest (using time-dependent covariates, where applicable) and time to death, adjusting for possible confounders. Results: There were 50 deaths in the cohort after a median of 25.2 months of follow-up. The cumulative incidences of death were 7% at 1 year and 16% at 2 years. In Cox proportional hazards regression analyses adjusting for demographic, clinical, and immunological variables, HIV-associated dementia (hazard rate, 6.10; P = .001) was significantly associated with time to death; (log) plasma MCP-1 level (hazard rate, 3.38; P = .08) trended toward significance. Conclusion: In patients with advanced HIV infection, HIV-associated dementia is an independent predictor of time to death. Before the widespread use of highly active antiretroviral therapy (HAART), plasma human immunodeficiency virus (HIV) RNA level and CD4 cell count were considered the best biological prognostic markers of morbidity and survival for patients with HIV infection.1 The use of HAART has resulted in a significant and sustained decrease in HIV-associated morbidity and mortality, 2 presumably mediated through superior virological control enabling a more robust and durable immune reconstitution. Consequently, the predictive value of plasma HIV RNA level seems to have been attenuated by the potency of the new antiretroviral (ARV) therapies.3 Several other markers of immune activation, including neopterin,4 β2-microglobulin,5 and plasma tumor necrosis factor α (TNF-α),6 have been identified as potential prognostic markers for HIV-associated morbidity and mortality, but the results from these studies are conflicting. Possible associations were recently reported between plasma TNF-α and cerebrospinal fluid macrophage chemoattractant protein 1 (MCP-1) levels and the development of HIV-associated dementia (HIVD) in a HAART-experienced cohort with advanced HIV infection.7 Clinical and demographic criteria have been correlated with HIV-associated morbidity and mortality. Pre–HAART era studies8-11 identified cognitive impairment and psychomotor slowing as predictors of mortality. These publications did not describe the relationship between the syndromic diagnosis of HIVD and mortality, but another pre–HAART era study12 failed to find a significant association between onset of dementia and mortality. The objective of this study was to determine whether neurocognitive status and baseline levels of plasma and cerebrospinal fluid TNF-α, MCP-1, matrix metalloproteinase 2 (MMP-2), or macrophage colony-stimulating factor (M-CSF) are associated with time to death in a well-characterized cohort of HAART-experienced subjects with advanced HIV. Methods: Participants in this study were enrolled in the Northeast AIDS Dementia Study cohort.7 From April 14, 1998, through July 22, 2002, we recruited ambulatory subjects who were seropositive for HIV and had a CD4+ cell count of less than 200/μL (or <300/μL but with cognitive impairment) at Columbia University, New York, NY; University of Rochester, Rochester, NY; The Johns Hopkins University, Baltimore, Md; and (beginning in 1999) Northwestern University, Chicago, Ill. Subjects with concurrent or past schizophrenia, severe affective disorder, central nervous system infection, or other chronic neurological disorders were excluded; subjects were not evaluated if they were under the influence of alcohol or illicit drugs, as judged by the examining physician. Subjects underwent semiannual evaluations. Institutional review board and ethics committee approval was obtained at each institution, and informed consent was obtained from each participant. Clinical and demographic assessments: The clinical and demographic data collected included the following: age, sex, race/ethnicity, years of education, use of illicit drugs, date of HIV diagnosis, history of AIDS-defining illness (clinical category C), and type of ARV use. The type of ARV use was classified as none, 1 to 2 ARVs, or 3 ARVs or more (HAART). Age, years of education, and duration of HIV were treated as continuous variables and sex, race/ethnicity, use of illicit drugs, history of AIDS-defining illness, and type of ARV use were treated as categorical variables in the analyses. Neurocognitive assessments: The clinical evaluations focused on the signs and symptoms associated with HIVD and included a neurological examination, neuropsychological battery, functional assessment, and psychiatric assessment, as previously described.7 The neuropsychological battery included 8 tests covering the following 6 cognitive domains: verbal memory (Rey Auditory Verbal Learning Test), visual memory (Rey-Osterrieth Complex Figure Delayed Recall Test), construction (Rey-Osterrieth Complex Figure Copy), psychomotor (Digit Symbol Test), motor speed (Grooved Pegboard and Timed Gait), and frontal systems (Verbal Fluency and Odd-Man-Out Test).7 Performance on each test was referenced to age- and education-appropriate norms where available.13,14 Based on the results from these clinical assessments, subjects were categorized as nonimpaired, as having minor cognitive and motor disorder (MCMD), or as demented (having HIVD) using the American Academy of Neurology criteria.15 Neurocognitive status was treated as a categorical variable in the analyses. For purposes of enrollment, cognitive impairment was defined as performing at least 1 SD below the mean on 2 separate neuropsychological tests (or 2 SDs below the mean on 1 test). However, if Timed Gait was the only test for which a score was 2 SDs below the mean, then criteria for cognitive impairment were not met. Laboratory assessments: Baseline assessments of CD4 cell count, hemoglobin level, and levels of HIV RNA, MCP-1, TNF-α, M-CSF, and MMP-2 in plasma and cerebrospinal fluid were performed. In addition, CD4 cell count, hemoglobin level, and plasma and cerebrospinal fluid HIV RNA levels were measured at follow-up visits (cerebrospinal fluid was measured only annually). The HIV RNA levels were determined using the NucliSens QT assay (logarithm of odds, 80 copies/mL; bioMerieux, Inc, Durham, NC); the TNF-α, MCP-1, M-CSF, and MMP-2 levels were determined using Quantikine ELISA kits (R&D Systems, Minneapolis, Minn). Values were log-transformed in base 10, except for CD4 cell count, for which the natural logarithm (ln) was used. All biological markers were treated as continuous variables in the analyses. Data analyses: The primary outcome for this study was time from study enrollment to death. Only subjects with at least 1 follow-up were included in the analyses. A subject was classified as deceased based on information from a friend, family member, medical record, or death certificate. Subjects not completing the study were classified as withdrawals. For subjects who withdrew or survived until the end of scheduled follow-up, follow-up time was censored at the last available visit. Baseline variables were compared among the deceased, those who completed follow-up, and those who withdrew from the study using t and χ2 tests. A Kaplan-Meier curve was constructed to estimate the cumulative incidence of death for subjects with at least 1 follow-up assessment. Associations between the independent variables and time to death were examined using Cox proportional hazards regression models. Independent variables with values that could change over time were treated as time-dependent covariates, except for plasma and cerebrospinal fluid immune markers, for which only baseline values were examined. Univariate analyses were performed on the independent variables. Next, Cox proportional hazards regression models were created to examine whether (in separate analyses) CD4 cell count, neurocognitive status (MCMD or HIVD), and plasma and cerebrospinal fluid levels of HIV RNA, MCP-1, TNF-α, MMP-2, and M-CSF were independent predictors of time to death, adjusting for the following core group of variables considered to be potential confounders: age, sex, hemoglobin level, HAART use (yes or no), race/ethnicity (nonwhite vs white), history of HIV-related illness, and National Adult Reading Test score (a measure of IQ). Finally, Cox proportional hazards regression models containing the core variables and various combinations of the immune markers, CD4 cell count, and neurocognitive status (nonimpaired, MCMD, or HIVD) were examined. All of the Cox regression models included site of enrollment as a stratification factor. Results: Of 396 subjects enrolled into the study, 329 (83%) had at least 1 follow-up visit. The median total duration of follow-up for the cohort was 25.2 months (interquartile range, 14.3-41.7 months). One hundred seventy-four subjects (53%) completed all scheduled follow-up visits, 50 subjects (15%) died, and 105 subjects (32%) withdrew prematurely. The chief reason (90%) for withdrawal was loss to follow-up (eg, unavailability or chose not to continue among other reasons). Those who withdrew had a shorter median total duration of follow-up (19.5 months [interquartile range, 12.0-29.5 months]). The baseline characteristics of the cohort, overall and stratified by follow-up status (completed, died, or withdrew), are summarized in Table 1. The estimated cumulative incidences of death were 7% at 1 year and 16% at 2 years (Figure). Compared with subjects who completed follow-up, those who died were more likely at baseline to have had an AIDS-defining illness, a lower hemoglobin level, a lower (ln) CD4 cell count, an abnormal neurocognitive status (MCMD or HIVD), a higher (log) plasma HIV RNA level, and higher (log) plasma and cerebrospinal fluid MCP-1 levels. In univariate analyses, significant associations were found between time to death and HAART use, HIVD, hemoglobin level, (ln) CD4 cell count, history of AIDS-defining illness, (log) plasma MCP-1 level, (log) plasma HIV RNA level, and (log) cerebrospinal fluid MCP-1 level. These results are summarized in Table 2. In the Cox proportional hazards regression analyses adjusting for the 7 core variables, the following were significantly associated with time to death: HIVD (Table 3, model A), (log) plasma MCP-1 level (Table 4, model A), and (ln) CD4 cell count (hazard rate [HR], 0.64; 95% confidence interval [CI], 0.51-0.81; P<.001). Not significant were MCMD (Table 3, model A), (log) cerebrospinal fluid MCP-1 level (Table 4, model A), (log) plasma HIV RNA level (HR, 1.17; 95% CI, 0.92-1.48; P = .19), and (log) cerebrospinal fluid HIV RNA level (HR, 0.89; 95% CI, 0.60-1.33; P = .58). In models adjusting for the 7 core variables and (ln) CD4 cell count, HIVD (Table 3, model B) was significantly associated with time to death. Not significant were MCMD (Table 3, model B), (log) plasma MCP-1 level (Table 4, model B), and (log) cerebrospinal fluid MCP-1 level (Table 4, model B). In a model containing the 7 core variables, neurocognitive status (MCMD or HIVD), (1n) CD4 cell count, and (log) MCP-1 (plasma or CSF), the following were significantly associated with time to death: HIVD (Table 3A, model C) and (1n) CD4 (HR, 0.73; 95% CI, 0.56-0.96; P = .02). Not significant were MCMD (Table 3, model C), (log) plasma MCP-1 (Table 4, model D), and (log) CSF MCP-1 (Table 4, model D). Of the 1517 subject-visits that occurred, there were 427 subject-visits (28%) by 196 subjects (60%) at which the subject met criteria for HIVD. The most common neuropsychological test abnormalities found in subjects with HIVD at these visits were in the domains of verbal memory (Rey Auditory Verbal Learning Test: 72% ≥1 SD below age- and education-appropriate norms and 38% ≥2 SDs below norms), construction (Rey-Osterrieth Complex Figure Copy: 66% ≥1 SD below norms and 48% ≥2 SDs below norms), and motor speed (Grooved Pegboard: 63% ≥1 SD below norms and 38% ≥2 SDs below norms; Timed Gait: 59% ≥1.5 SDs below norms and 41% ≥2.5 SDs below norms)