Personal protective equipment (PPE) can potentiate heat stress, which may have a negative impact on the wearer's performance, safety and well-being. In view of this, a survey was distributed to ...healthcare workers (HCWs) required to wear PPE during the coronavirus disease 2019 pandemic in the UK to evaluate perceived levels of heat stress and its consequences. Respondents reported experiencing several heat-related illness symptoms, and heat stress impaired both cognitive and physical performance. The majority of respondents stated that wearing PPE made their job more difficult. These, and additional, responses suggest that modification to current working practices is required urgently to improve the resilience of HCWs to wearing PPE during pandemics.
Our understanding of the natural history of idiopathic Parkinson's disease (PD) remains limited. In the era of potential disease modifying therapies, there is an urgent need for studies assessing the ...natural evolution of treated PD from onset so that relevant outcome measures can be identified for clinical trials. No previous studies have charted progression in unselected patients followed from the point of diagnosis.
A representative cohort of 132 PD patients was followed from diagnosis for up to 7.9 years (mean 5.2 years). Comprehensive clinical and neuropsychological evaluations were performed every 18 months. Disease progression was evaluated using well validated clinical measures (motor progression and development of dyskinesia on the Unified PD Rating Scale and Hoehn-Yahr scale, dementia onset according to DSM-IV criteria). Multi-level linear modelling was used to chart the nature and rate of progression in parkinsonian symptoms and signs over time. The prognostic importance of baseline demogr‘aphic, clinical and genetic variables was evaluated using survival analysis.
Axial (gait and postural) symptoms evolve more rapidly than other motor features of PD and appear to be the best index of disease progression. Conversely, conventional outcome measures are relatively insensitive to change over time. Earlier onset of postural instability (Hoehn-Yahr stage 3) is strongly associated with increased age at disease onset and has a significant impact on quality of life.
Dementia risk is associated with increased age, impaired baseline semantic fluency and the MAPT H1/H1 genotype. The efficacy of disease modifying therapies may be more meaningfully assessed in terms of their effects in delaying the major milestones of PD, such as postural instability and dementia, since it is these that have the greatest impact on patients.
The power of forecasts to advance ecological theory Lewis, Abigail S. L.; Rollinson, Christine R.; Allyn, Andrew J. ...
Methods in ecology and evolution,
March 2023, 2023-03-00, 20230301, 2023-03-01, Letnik:
14, Številka:
3
Journal Article
Recenzirano
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Ecological forecasting provides a powerful set of methods for predicting short‐ and long‐term change in living systems. Forecasts are now widely produced, enabling proactive management for many ...applied ecological problems. However, despite numerous calls for an increased emphasis on prediction in ecology, the potential for forecasting to accelerate ecological theory development remains underrealized.
Here, we provide a conceptual framework describing how ecological forecasts can energize and advance ecological theory. We emphasize the many opportunities for future progress in this area through increased forecast development, comparison and synthesis.
Our framework describes how a forecasting approach can shed new light on existing ecological theories while also allowing researchers to address novel questions. Through rigorous and repeated testing of hypotheses, forecasting can help to refine theories and understand their generality across systems. Meanwhile, synthesizing across forecasts allows for the development of novel theory about the relative predictability of ecological variables across forecast horizons and scales.
We envision a future where forecasting is integrated as part of the toolset used in fundamental ecology. By outlining the relevance of forecasting methods to ecological theory, we aim to decrease barriers to entry and broaden the community of researchers using forecasting for fundamental ecological insight.
Background. Non-dialysis-dependent chronic kidney disease (CKD) is related to cognitive impairment. Previous studies have not explored the extent of impairment across multiple cognitive domains. We ...examined the range of specific cognitive abilities affected by CKD and whether the associations of CKD with cognition were eliminated by statistical control for cardiovascular disease correlates of CKD. Methods. We performed a community-based cross-sectional study with 923 individuals free from dementia and end-stage renal disease. Two groups were defined based on estimated glomerular filtration rate (eGFR): eGFR<60 mL/min/1.73 m2 versus eGFR ≥ 60 mL/min/1.73 m2. Outcome measures were scores from multiple clinical tests of specific cognitive abilities. The GFR classifications and serum creatinine levels were related to measures of cognitive performance using logistic and linear regression analyses with three sets of covariates: (1) basic (age, education, gender and race); (2) basic+risk factors for cardiovascular disease (CVD) and (3) basic+risk factors for CVD+stroke. Results. An eGFR <60 mL/min/1.73 m2 was present in 142 (15.4%) individuals; the mean (SD) eGFR in this subgroup was 49.7 (10.7). CKD was related to lower cognitive performance despite adjustment for CVD risk factors (CVD-RF). Adjusting for CVD-RF and stroke, odds ratios and 95% confidence intervals associated with performing in the lowest quartile of the distribution of the Global, Visual–Spatial Organization/Memory and Scanning and Tracking scores for the eGFR < 60 group were 1.97 (1.25, 3.10); 1.88 (1.21, 2.93) and 1.83 (1.56, 2.87), P < 0.01 with eGFR ≥ 60 group as the reference group. Conclusions. Global performance and specific cognitive functions are negatively affected early in CKD. Targeted screening for cognitive deficits in kidney disease patients early in their disease course may be warranted.
Immunotherapy using either checkpoint blockade or the adoptive transfer of antitumor lymphocytes has shown effectiveness in treating cancers with high levels of somatic mutations-such as melanoma, ...smoking-induced lung cancers and bladder cancer-with little effect in other common epithelial cancers that have lower mutation rates, such as those arising in the gastrointestinal tract, breast and ovary
. Adoptive transfer of autologous lymphocytes that specifically target proteins encoded by somatically mutated genes has mediated substantial objective clinical regressions in patients with metastatic bile duct, colon and cervical cancers
. We present a patient with chemorefractory hormone receptor (HR)-positive metastatic breast cancer who was treated with tumor-infiltrating lymphocytes (TILs) reactive against mutant versions of four proteins-SLC3A2, KIAA0368, CADPS2 and CTSB. Adoptive transfer of these mutant-protein-specific TILs in conjunction with interleukin (IL)-2 and checkpoint blockade mediated the complete durable regression of metastatic breast cancer, which is now ongoing for >22 months, and it represents a new immunotherapy approach for the treatment of these patients.
We report here the adoptive transfer, to patients with metastatic melanoma, of highly selected tumor-reactive T cells directed against overexpressed self-derived differentiation antigens after a ...nonmyeloablative conditioning regimen. This approach resulted in the persistent clonal repopulation of T cells in those cancer patients, with the transferred cells proliferating in vivo, displaying functional activity, and trafficking to tumor sites. This led to regression of the patients' metastatic melanoma as well as to the onset of autoimmune melanocyte destruction. This approach presents new possibilities for the treatment of patients with cancer as well as patients with human immunodeficiency virus-related acquired immunodeficiency syndrome and other infectious diseases.
Our decisions are based on parallel and competing systems of goal-directed and habitual learning, systems which can be impaired in pathological behaviours. Here we focus on the influence of ...motivation and compare reward and loss outcomes in subjects with obsessive-compulsive disorder (OCD) on model-based goal-directed and model-free habitual behaviours using the two-step task. We further investigate the relationship with acquisition learning using a one-step probabilistic learning task. Forty-eight OCD subjects and 96 healthy volunteers were tested on a reward and 30 OCD subjects and 53 healthy volunteers on the loss version of the two-step task. Thirty-six OCD subjects and 72 healthy volunteers were also tested on a one-step reversal task. OCD subjects compared with healthy volunteers were less goal oriented (model-based) and more habitual (model-free) to reward outcomes with a shift towards greater model-based and lower habitual choices to loss outcomes. OCD subjects also had enhanced acquisition learning to loss outcomes on the one-step task, which correlated with goal-directed learning in the two-step task. OCD subjects had greater stay behaviours or perseveration in the one-step task irrespective of outcome. Compulsion severity was correlated with habitual learning in the reward condition. Obsession severity was correlated with greater switching after loss outcomes. In healthy volunteers, we further show that greater reward magnitudes are associated with a shift towards greater goal-directed learning further emphasizing the role of outcome salience. Our results highlight an important influence of motivation on learning processes in OCD and suggest that distinct clinical strategies based on valence may be warranted.
Streptococcus gallolyticus (SG) is a Gram-positive cocci found as commensal gut flora in animals and humans. SG has emerged as a cause of disease in young poults between 1 and 3 wk of age. SG is ...associated with septicemia resulting in acute mortality with no premonitory signs in turkeys. Three SG isolates were obtained from clinical field cases of acute septicemia of commercial turkeys and used in three independent experiments. In Experiment 1, embryos were inoculated 25 d of embryogenesis with varying concentrations of SG1, SG2, or SG3. In Experiment 2, day of hatch, poults were inoculated with varying concentrations using different routes of administration of SG1, SG2, or SG3. In Experiment 3, day of hatch, poults were inoculated with only isolate SG1 using different paths. Poults were randomly selected for necropsy on d 8 and d 15 and sampled to collect spleen, heart, and liver for SG on d 21, the remaining poults were necropsied and cultured. Samples were plated on Columbia nalidixic acid and colistin agar (CNA) (40°C, 18–24 h). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) confirmed suspect colonies. Data were analyzed using the chi-square test of independence, testing all possible combinations to determine significance (P < 0.05). Weight data were subjected to ANOVA using JMP with significance (P < 0.05). No differences were found in BW or BWG on d 0, 8, 15, or 22. Splenomegaly, focal heart necrosis, and pericarditis were observed in all groups in experiments 1 through 3. In Experiment 3, only airsacculitis was observed in a negative control in separate isolation (P > 0.05). On d 21 of Experiment 3, increased (P < 0.05) recovery of SG from spleens were observed in co-housed negative controls, as well as poults challenged by oral gavage (P > 0.05 for d 7 and d 14). These results confirm numerous previous studies indicating that SG subsp. pasteurianus is a primary infectious microorganism that causes septicemia in young poults.
Diabetic kidney disease (DKD) is one of the most frequent complications in diabetes associated with substantial morbidity and mortality. To accelerate DKD risk factor discovery, we present an ...ensemble feature selection approach to identify a robust set of discriminant factors using electronic medical records (EMRs).
We identified a retrospective cohort of 15 645 adult patients with type 2 diabetes, excluding those with pre-existing kidney disease, and utilized all available clinical data types in modeling. We compared 3 machine-learning-based embedded feature selection methods in conjunction with 6 feature ensemble techniques for selecting top-ranked features in terms of robustness to data perturbations and predictability for DKD onset.
The gradient boosting machine (GBM) with weighted mean rank feature ensemble technique achieved the best performance with an AUC of 0.82 95%-CI, 0.81-0.83 on internal validation and 0.71 95%-CI, 0.68-0.73 on external temporal validation. The ensemble model identified a set of 440 features from 84 872 unique clinical features that are both predicative of DKD onset and robust against data perturbations, including 191 labs, 51 visit details (mainly vital signs), 39 medications, 34 orders, 30 diagnoses, and 95 other clinical features.
Many of the top-ranked features have not been included in the state-of-art DKD prediction models, but their relationships with kidney function have been suggested in existing literature.
Our ensemble feature selection framework provides an option for identifying a robust and parsimonious feature set unbiasedly from EMR data, which effectively aids in knowledge discovery for DKD risk factors.
Summary
Background:
Adoption of a common data model across health systems is a key infrastructure requirement to allow large scale distributed comparative effectiveness analyses. There are a growing ...number of common data models (CDM), such as Mini-Sentinel, and the Observational Medical Outcomes Partnership (OMOP) CDMs.
Objective:
In this case study, we describe the challenges and opportunities of a study specific use of the OMOP CDM by two health systems and describe three comparative effectiveness use cases developed from the CDM.
Methods:
The project transformed two health system databases (using crosswalks provided) into the OMOP CDM. Cohorts were developed from the transformed CDMs for three comparative effectiveness use case examples. Administrative/billing, demographic, order history, medication, and laboratory were included in the CDM transformation and cohort development rules.
Results:
Record counts per person month are presented for the eligible cohorts, highlighting differences between the civilian and federal datasets, e.g. the federal data set had more outpatient visits per person month (6.44 vs. 2.05 per person month). The count of medications per person month reflected the fact that one system‘s medications were extracted from orders while the other system had pharmacy fills and medication administration records. The federal system also had a higher prevalence of the conditions in all three use cases. Both systems required manual coding of some types of data to convert to the CDM.
Conclusion:
The data transformation to the CDM was time consuming and resources required were substantial, beyond requirements for collecting native source data. The need to manually code subsets of data limited the conversion. However, once the native data was converted to the CDM, both systems were then able to use the same queries to identify cohorts. Thus, the CDM minimized the effort to develop cohorts and analyze the results across the sites.
FitzHenry F, Resnic FS, Robbins SL, Denton J, Nookala L, Meeker D, Ohno-Machado L, Matheny ME. A Case Report on Creating a Common Data Model for Comparative Effectiveness with the Observational Medical Outcomes Partnership. Appl Clin Inform 2015; 6: 536–547
http://dx.doi.org/10.4338/ACI-2014-12-CR-0121
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