Measurement batch differences and between-batch conversion of Alzheimer's disease cerebrospinal fluid biomarker values

Introduction: Batch differences in cerebrospinal fluid (CSF) biomarker measurement can introduce bias into analyses for Alzheimer's disease studies. We evaluated and adjusted for batch differences using statistical methods. Methods: A total of 792 CSF samples from 528 participants were assayed in three batches for 12 biomarkers and 3 biomarker ratios. Batch differences were assessed using Bland-Altman plot, paired t test, Pitman-Morgan test, and linear regression. Generalized linear models were applied to convert CSF values between batches. Results: We found statistically significant batch differences for all biomarkers and ratios, except that neurofilament light was comparable between batches 1 and 2. The conversion models generally had high R2 except for converting P-tau between batches 1 and 3. Discussion: Between-batch conversion allows harmonized CSF values to be used in the same analysis. Such method may be applied to adjust for other sources of variability in measuring CSF or other types of biomarkers

Prostate cancer in male BRCA1 and BRCA2 mutation carriers has a more aggressive phenotype

There is a high and rising prevalence of prostate cancer (PRCA) within the male population of the United Kingdom. Although the relative risk of PRCA is higher in male BRCA2 and BRCA1 mutation carriers, the histological characteristics of this malignancy in these groups have not been clearly defined. We present the histopathological findings in the first UK series of BRCA1 and BRCA2 mutation carriers with PRCA. The archived histopathological tissue sections of 20 BRCA1/2 mutation carriers with PRCA were collected from histopathology laboratories in England, Ireland and Scotland. The cases were matched to a control group by age, stage and serum PSA level of PRCA cases diagnosed in the general population. Following histopathological evaluation and re-grading according to current conventional criteria, Gleason scores of PRCA developed by BRCA1/2 mutation carriers were identified to be significantly higher (Gleason scores 8, 9 or 10, P=0.012) than those in the control group. Since BRCA1/2 mutation carrier status is associated with more aggressive disease, it is a prognostic factor for PRCA outcome. Targeting screening to this population may detect disease at an earlier clinical stage which may therefore be beneficial

Outcome of paediatric intensive care survivors

The development of paediatric intensive care has contributed to the improved survival of critically ill children. Physical and psychological sequelae and consequences for quality of life (QoL) in survivors might be significant, as has been determined in adult intensive care unit (ICU) survivors. Awareness of sequelae due to the original illness and its treatment may result in changes in treatment and support during and after the acute phase. To determine the current knowledge on physical and psychological sequelae and the quality of life in survivors of paediatric intensive care, we undertook a computerised comprehensive search of online databases for studies reporting sequelae in survivors of paediatric intensive care. Studies reporting sequelae in paediatric survivors of cardiothoracic surgery and trauma were excluded, as were studies reporting only mortality. All other studies reporting aspects of physical and psychological sequelae were analysed. Twenty-seven studies consisting of 3,444 survivors met the selection criteria. Distinct physical and psychological sequelae in patients have been determined and seemed to interfere with quality of life. Psychological sequelae in parents seem to be common. Small numbers, methodological limitations and quantitative and qualitative heterogeneity hamper the interpretation of data. We conclude that paediatric intensive care survivors and their parents have physical and psychological sequelae affecting quality of life. Further well-designed prospective studies evaluating sequelae of the original illness and its treatment are warranted

Early Treatment with Basal Insulin Glargine in People with Type 2 Diabetes: Lessons from ORIGIN and Other Cardiovascular Trials

Dysglycemia results from a deficit in first-phase insulin secretion compounded by increased insulin insensitivity, exposing beta cells to chronic hyperglycemia and excessive glycemic variability. Initiation of intensive insulin therapy at diagnosis of type 2 diabetes mellitus (T2DM) to achieve normoglycemia has been shown to reverse glucotoxicity, resulting in recovery of residual beta-cell function. The United Kingdom Prospective Diabetes Study (UKPDS) 10-year post-trial follow-up reported reductions in cardiovascular outcomes and all-cause mortality in persons with T2DM who initially received intensive glucose control compared with standard therapy. In the cardiovascular outcome trial, outcome reduction with an initial glargine intervention (ORIGIN), a neutral effect on cardiovascular disease was observed in the population comprising prediabetes and T2DM. Worsening of glycemic control was prevented over the 6.7 year treatment period, with few serious hypoglycemic episodes and only moderate weight gain, with a lesser need for dual or triple oral treatment versus standard care. Several other studies have also highlighted the benefits of early insulin initiation as first-line or add-on therapy to metformin. The decision to introduce basal insulin to metformin must, however be individualized based on a risk-benefit analysis. The landmark ORIGIN trial provides many lessons relating to the concept and application of early insulin therapy for the prevention and safe and effective induction and maintenance of glycemic control in type 2 diabetes

Outcomes research in the development and evaluation of practice guidelines

BACKGROUND: Practice guidelines have been developed in response to the observation that variations exist in clinical medicine that are not related to variations in the clinical presentation and severity of the disease. Despite their widespread use, however, practice guideline evaluation lacks a rigorous scientific methodology to support its development and application. DISCUSSION: Firstly, we review the major epidemiological foundations of practice guideline development. Secondly, we propose a chronic disease epidemiological model in which practice patterns are viewed as the exposure and outcomes of interest such as quality or cost are viewed as the disease. Sources of selection, information, confounding and temporal trend bias are identified and discussed. SUMMARY: The proposed methodological framework for outcomes research to evaluate practice guidelines reflects the selection, information and confounding biases inherent in its observational nature which must be accounted for in both the design and the analysis phases of any outcomes research study

Climate Change, Coral Reef Ecosystems, and Management Options for Marine Protected Areas

Marine protected areas (MPAs) provide place-based management of marine ecosystems through various degrees and types of protective actions. Habitats such as coral reefs are especially susceptible to degradation resulting from climate change, as evidenced by mass bleaching events over the past two decades. Marine ecosystems are being altered by direct effects of climate change including ocean warming, ocean acidification, rising sea level, changing circulation patterns, increasing severity of storms, and changing freshwater influxes. As impacts of climate change strengthen they may exacerbate effects of existing stressors and require new or modified management approaches; MPA networks are generally accepted as an improvement over individual MPAs to address multiple threats to the marine environment. While MPA networks are considered a potentially effective management approach for conserving marine biodiversity, they should be established in conjunction with other management strategies, such as fisheries regulations and reductions of nutrients and other forms of land-based pollution. Information about interactions between climate change and more “traditional” stressors is limited. MPA managers are faced with high levels of uncertainty about likely outcomes of management actions because climate change impacts have strong interactions with existing stressors, such as land-based sources of pollution, overfishing and destructive fishing practices, invasive species, and diseases. Management options include ameliorating existing stressors, protecting potentially resilient areas, developing networks of MPAs, and integrating climate change into MPA planning, management, and evaluation

Texture and nanostructural engineering of conjugated conducting and semiconducting polymers

© 2020 The Author(s) Conducting polymers have attracted tremendous attention because of their unique characteristics, such as metal-like conductivity, ionic conductivity, optical transparency, and mechanical flexibility. Texture and nanostructural engineering of conjugated conducting polymers provide an outstanding pathway to facilitate their adoption in a variety of technological applications, including energy storage and harvesting devices, flexible optoelectronic devices, and wearable electronic devices. Generally, obtaining high carrier mobility in the presence of high carrier density is challenging and requires precise control of the texture and nanostructure of conducting polymers to avoid the charge localization. Preferential semicrystalline orientation, π–π stacking distances, crystallite size, intra- and interchain couplings, intra- and intercrystallite connections, and grain boundaries are the key parameters that influence the charge carrier mobility and needs to be controlled by the synthesis parameters. This article provides a comprehensive overview of the recent texture and nanostructural engineering development of conducting polymers. In addition, this work describes the fundamental of charge carrier transport mechanisms in conducting polymers; and the latest progress on the optoelectronic characteristics of flexible transparent conductive electrodes based on conducting polymers is reported