Starch safety in resuscitation

This correspondence is in response to the article: Parrish A, Blockman M, Starch safety in resuscitation − when will we ever learn? S Afr Med J 2013;103(6):365-367. [http://dx.doi.org/10.7196/samj.6969] in three parts:1. Starch safety in resuscitation: Withdrawal of hydroxyethyl starch solutions − a plea for evidence. R E Hodgson, G A Richards, A C Lundgren, M G L Spruyt, J P Pretorius, L R Mathiva, R Dickerson, P D Gopalan 2. Starch safety in resuscitation: Plea for evidence. M F M James, I A Joubert, J L Piercy3. Starch safety in resuscitation: Response from A Parrish and M Blockma

Human Nasal Challenge with Streptococcus pneumoniae Is Immunising in the Absence of Carriage

Infectious challenge of the human nasal mucosa elicits immune responses that determine the fate of the host-bacterial interaction; leading either to clearance, colonisation and/or disease. Persistent antigenic exposure from pneumococcal colonisation can induce both humoral and cellular defences that are protective against carriage and disease. We challenged healthy adults intra-nasally with live 23F or 6B Streptococcus pneumoniae in two sequential cohorts and collected nasal wash, bronchoalveolar lavage (BAL) and blood before and 6 weeks after challenge. We hypothesised that both cohorts would successfully become colonised but this did not occur except for one volunteer. The effect of bacterial challenge without colonisation in healthy adults has not been previously assessed. We measured the antigen-specific humoral and cellular immune responses in challenged but not colonised volunteers by ELISA and Flow Cytometry. Antigen-specific responses were seen in each compartment both before and after bacterial challenge for both cohorts. Antigen-specific IgG and IgA levels were significantly elevated in nasal wash 6 weeks after challenge compared to baseline. Immunoglobulin responses to pneumococci were directed towards various protein targets but not capsular polysaccharide. 23F but not 6B challenge elevated IgG anti-PspA in BAL. Serum immunoglobulins did not increase in response to challenge. In neither challenge cohort was there any alteration in the frequencies of TNF, IL-17 or IFNγ producing CD4 T cells before or after challenge in BAL or blood. We show that simple, low dose mucosal exposure with pneumococci may immunise mucosal surfaces by augmenting anti-protein immunoglobulin responses; but not capsular or cellular responses. We hypothesise that mucosal exposure alone may not replicate the systemic immunising effect of experimental or natural carriage in humans

Improving outcomes for women aged 70 years or above with early breast cancer: research programme including a cluster RCT

Background In breast cancer management, age-related practice variation is widespread, with older women having lower rates of surgery and chemotherapy than younger women, based on the premise of reduced treatment tolerance and benefit. This may contribute to inferior outcomes. There are currently no age- and fitness-stratified guidelines on which to base treatment recommendations. Aim We aimed to optimise treatment choice and outcomes for older women (aged ≥ 70 years) with operable breast cancer. Objectives Our objectives were to (1) determine the age, comorbidity, frailty, disease stage and biology thresholds for endocrine therapy alone versus surgery plus adjuvant endocrine therapy, or adjuvant chemotherapy versus no chemotherapy, for older women with breast cancer; (2) optimise survival outcomes for older women by improving the quality of treatment decision-making; (3) develop and evaluate a decision support intervention to enhance shared decision-making; and (4) determine the degree and causes of treatment variation between UK breast units. Design A prospective cohort study was used to determine age and fitness thresholds for treatment allocation. Mixed-methods research was used to determine the information needs of older women to develop a decision support intervention. A cluster-randomised trial was used to evaluate the impact of this decision support intervention on treatment choices and outcomes. Health economic analysis was used to evaluate the cost–benefit ratio of different treatment strategies according to age and fitness criteria. A mixed-methods study was used to determine the degree and causes of variation in treatment allocation. Main outcome measures The main outcome measures were enhanced age- and fitness-specific decision support leading to improved quality-of-life outcomes in older women (aged ≥ 70 years) with early breast cancer

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

A call for a digital Community Psychology

Community Psychology has seemingly been left behind on the digital front. For one reason or another, the connections between Community Psychology, digital technologies and social media remain unplugged. We are calling for a new “Digital Community Psychology”. In this chapter, we apply a digital autoethnographic method to generate knowledge about Community Psychology, social media and digital technologies. We reflect on what “Digital Community Psychology” might entail in email “call and response” exchanges. We use our emails to one another as data to explore and outline the disconnect between Community Psychology, digital technologies and social media. Second, we examine Community Psychology’s existence against “mainstream psychology” to make the case for critical forms of psychology to interrogate and render accountable the powerful advances in the digitalisation and datafication of society, institutions and social practices. To push community psychological work around human–technology relations further, we draw upon ideas and concepts from transdisciplinary fields of knowledge, mainly from the scholarly work that is being badged together as feminist new materialism and posthumanism. Then we theorise social media communities: what are they becoming and what new subjectivities reflect our networked lives? Lastly, we include a case study that highlights how making social media for social activism falls within the remit of practicing Digital Community Psychology

A Conceptual Framework for Assessment Literacy: Opportunities for Physical Education Teacher Education

Although more nuanced understandings of assessment have been proposed in the physical education literature, assessment practices remain relatively underdeveloped, and when used, tend to focus on traditional, summative evaluations of learning. However, physical education teacher education programs can be used as an intervention to help pre-service teachers develop assessment knowledge and skill. Toward this end, the purpose of this article is to propose an evidence-based framework for helping pre-service teachers develop assessment literacy that is rooted in occupational socialization theory. The framework provides a four-phase approach to integrating assessment into teacher education, and includes suggestions for how physical education teacher educators can progressively help build pre-service teachers’ assessment knowledge in line with the focus given to instruction and planning. These suggestions acknowledge the technical and sociocultural aspects of learning to use assessment. Implications are discussed along with the need to help graduating pre-service teachers transfer lessons learned into the workplace

ADAMTSL2 protein and a soluble biomarker signature identify significant and advanced fibrosis in adults with NAFLD

Abstract Aims and background: Identifying fibrosis in non-alcoholic fatty liver disease (NAFLD) is essential to predict liver-related outcomes and inform treatment decisions. A protein-based signature of fibrosis could serve as a valuable, non-invasive diagnostic tool. This study sought to identify circulating proteins associated with fibrosis in NAFLD. Methods: We used aptamer-based proteomics to measure 4783 proteins in two cohorts (Cohort A and B). Targeted, quantitative assays coupling aptamer-based protein pull down and mass spectrometry (SPMS) validated the profiling results in a bariatric and NAFLD cohort (Cohort C and D, respectively). Generalized linear modelling-logistic regression assessed the candidate proteins to classify fibrosis. Results: From the multiplex profiling, 16 proteins differed significantly by fibrosis in cohorts A (n=62) and B (n=98). Quantitative and robust SPMS assays were developed for 8 proteins and validated in Cohorts C (n=71) and D (n=84). The protein A disintegrin and metalloproteinase with thrombospondin motifs like 2 (ADAMTSL2) accurately distinguished NAFL/NASH with fibrosis stage 0-1 (F0-1) from at-risk NASH with fibrosis stage 2-4 with an AUROC of 0.83 and 0.86 in Cohorts C and D, respectively, and from NASH with significant fibrosis (F2-3) with an AUROC of 0.80 and 0.83 in Cohorts C and D, respectively. An 8-protein panel distinguished NAFL/NASH F0-1 from at-risk NASH (AUROC 0.90 and 0.87 in Cohort C and D, respectively) and NASH F2-3 (AUROC 0.89 and 0.83 in Cohorts C and D, respectively). The 8-protein panel and ADAMTSL2 protein had superior performance to the NAFLD fibrosis score and Fibrosis-4 score. Conclusion: The ADAMTSL2 protein and an 8-protein soluble biomarker panel are highly associated with at-risk NASH and significant fibrosis with superior performance to standard of care fibrosis scores. Lay summary: Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of liver disease worldwide. Diagnosing NAFLD and identifying fibrosis (scarring of the liver) currently requires a liver biopsy. Our study identified novel proteins found in blood which may identify fibrosis without the need for a liver biopsy

Differentiation of Subjective Cognitive Decline, Mild Cognitive Impairment, and Dementia Using qEEG/ERP-Based Cognitive Testing and Volumetric MRI in an Outpatient Specialty Memory Clinic.

BACKGROUND: Distinguishing between subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia in a scalable, accessible way is important to promote earlier detection and intervention. OBJECTIVE: We investigated diagnostic categorization using an FDA-cleared quantitative electroencephalographic/event-related potential (qEEG/ERP)-based cognitive testing system (eVox® by Evoke Neuroscience) combined with an automated volumetric magnetic resonance imaging (vMRI) tool (Neuroreader® by Brainreader). METHODS: Patients who self-presented with memory complaints were assigned to a diagnostic category by dementia specialists based on clinical history, neurologic exam, neuropsychological testing, and laboratory results. In addition, qEEG/ERP (n = 161) and quantitative vMRI (n = 111) data were obtained. A multinomial logistic regression model was used to determine significant predictors of cognitive diagnostic category (SCD, MCI, or dementia) using all available qEEG/ERP features and MRI volumes as the independent variables and controlling for demographic variables. Area under the Receiver Operating Characteristic curve (AUC) was used to evaluate the diagnostic accuracy of the prediction models. RESULTS: The qEEG/ERP measures of Reaction Time, Commission Errors, and P300b Amplitude were significant predictors (AUC = 0.79) of cognitive category. Diagnostic accuracy increased when volumetric MRI measures, specifically left temporal lobe volume, were added to the model (AUC = 0.87). CONCLUSION: This study demonstrates the potential of a primarily physiological diagnostic model for differentiating SCD, MCI, and dementia using qEEG/ERP-based cognitive testing, especially when combined with volumetric brain MRI. The accessibility of qEEG/ERP and vMRI means that these tools can be used as adjuncts to clinical assessments to help increase the diagnostic certainty of SCD, MCI, and dementia