From words to action

At the end of the Brussels Symposium on Sexual Violence inConflict and Beyond in June 2006, delegates drew up a Callto Action.1 We urge everyone to respond to this challenge

Hypoglycaemia Among Insulin-Treated Patients with Diabetes: Evaluation of the United Arab Emirates cohort of the International Operations-Hypoglycaemia Assessment Tool study

Objectives: This study aimed to evaluate the incidence of hypoglycaemia among insulin-treated patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) from the United Arab Emirates (UAE) cohort of the non-interventional International Operations-Hypoglycaemia Assessment Tool study. Methods: This cross-sectional observational study took place at 25 patient care centres in the UAE from October 2014 to May 2015. All adult patients with T1DM or T2DM who had been treated with insulin for >12 months were included. Self-assessment questionnaires and patient diaries were used to determine the incidence of documented hypoglycaemia both prospectively (four weeks after baseline) and retrospectively (six months and four weeks before baseline for severe and non-severe hypoglycaemic events, respectively). Results: A total of 325 patients were enrolled in the study, of which 82 (25.2%) had T1DM and 243 (74.8%) had T2DM. Among patients with T1DM, 71.4% reported hypoglycaemic events retrospectively, with an incidence rate (IR) of 102.8 events per patient-year (PY), while 95% reported hypoglycaemic events prospectively, with an IR of 63.1 events per PY. Additionally, 56.3% of patients with T2DM reported hypoglycaemic events retrospectively, with an IR of 42.2 events per PY, while 91.9% reported hypoglycaemic events prospectively, with an IR of 33.3 events per PY. Conclusion: The prevalence and incidence of hypoglycaemia were high among insulin-treated patients with T1DM and T2DM in the UAE. Individualised glycaemic goals, patient education and blood glucose monitoring may help to reduce the incidence of hypoglycaemia in this population. Keywords: Hypoglycemia; Insulin; Type 1 Diabetes Mellitus; Type 2 Diabetes Mellitus; United Arab Emirates

Phylogenomics and species delimitation for effective conservation of manta and devil rays

Practical biodiversity conservation relies on delineation of biologically meaningful units. Manta and devil rays (Mobulidae) are threatened worldwide, yet morphological similarities and a succession of recent taxonomic changes impede the development of an effective conservation strategy. Here, we generate genome‐wide single nucleotide polymorphism (SNP) data from a geographically and taxonomically representative set of manta and devil ray samples to reconstruct phylogenetic relationships and evaluate species boundaries under the general lineage concept. We show that nominal species units supported by alternative data sources constitute independently evolving lineages, and find robust evidence for a putative new species of manta ray in the Gulf of Mexico. Additionally, we uncover substantial incomplete lineage sorting indicating that rapid speciation together with standing variation in ancestral populations has driven phylogenetic uncertainty within Mobulidae. Finally, we detect cryptic diversity in geographically distinct populations, demonstrating that management below the species level may be warranted in certain species. Overall, our study provides a framework for molecular genetic species delimitation that is relevant to wide‐ranging taxa of conservation concern, and highlights the potential for genomic data to support effective management, conservation and law enforcement strategies

Pathways to a more peaceful and sustainable world:The transformative power of children in families

This article provides an overview of selected ongoing international efforts that have been inspired by Edward Zigler’s vision to improve programs and policies for young children and families in the United States. The efforts presented are in close alignment with three strategies articulated by Edward Zigler: (a) conduct research that will inform policy advocacy; (b) design, implement, and revise quality early child- hood development (ECD) programs; and (c) invest in building the next generation of scholars and advocates in child development. The intergenerational legacy left by Edward Zigler has had an impact on young children not only in the United States, but also across the globe. More needs to be done. We need to work together with a full commitment to ensure the optimal development of each child

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

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

De las palabras a la acción

Al final del Simposio sobre la Violencia Sexual durante y con posterioridad a los Conflictos, celebrado en Bruselas en junio de 2006, los delegados redactaron un Llamamiento a la Acción. Exhortamos a todos a que respondan a este desafío

Performance of chemically modified Tripoli in catalytic pyrolysis of date kernels

The use of natural minerals as catalysts in pyrolysis enhances the products’ yield and quality. However, natural minerals may lack the proper active sites to effectively catalyze the pyrolytic reactions. This paper addresses the performance of iron-chemically modified Jordanian Tripoli catalysts in the catalytic pyrolysis of date kernels. The Fe-chemically modified Tripoli catalyst was prepared by impregnation method at three different loadings (0.046, 1.788, 3.530 wt %). The effect of three different process variables, namely: pyrolysis temperature, heating rate and iron-loading on the performance of date kernels pyrolysis were investigated. Full factorial design methodology is employed to study the main effects of process variables and possible interaction effects among the process variables on the yields of the catalytic pyrolysis products. The maximum gas yield (197.8 ml/g-feed) was obtained at a pyrolysis temperature of 600 °C, heating rate of 20 °C/min and 3.530 wt% Fe-loading. The maximum bio-oil yield (42.88 wt%) was obtained at a pyrolysis temperature of 500 °C, heating rate of 60 °C/min and 1.788 wt% Fe-loading. The maximum bio-char yield (38.72 wt%) was obtained at a pyrolysis temperature of 400 °C, heating rate of 20 °C/min and catalytic pyrolysis using natural Tripoli. First order egression models are proposed to predict the product yields. The main implication of this study is that Fe-loaded Tripoli has effectively enhanced the quality of bio-oil

Process Optimization of Phytoantioxidant and Photoprotective Compounds from Carob Pods (Ceratonia siliqua L.) Using Ultrasonic Assisted Extraction Method

The current study first describes the extraction of phytoantioxidant polyphenols from Carob byproducts (pods) using maceration and heating-assisted extraction as traditional methods and ultrasonic-assisted extraction (UAE) as an innovative method to determine the most efficient extraction process in terms of four targeted responses: total phenolic content (TPC), antioxidant activities (TAC and DPPH), and photoprotective properties as measured by the sun protection factor (SPF). Second, we used response surface methodology (RSM) with a central composite rotatable design (CCDR) approach to investigate the influence of process variables (extraction time, extraction temperature, and solvent concentration) on UAE, which was found to be the most effective extraction technique in our study. Carob byproduct extracts had a TPC ranging from 6.21 to 21.92 mg GAE/g dw, a TAC ranging from 22.00 to 49.30 mg AAE/g dw, DPPH scavenging activity ranging from 56.35 to 90.50%, and SPF values ranging from 8.62 to 22.37. The optimal UAE conditions for maximum TPC, TAC, DPPH, and SPF responses were determined to be 38.90% ethanol, 53.90 °C, and 50.92 min. Using Carob as a source for sustainable and bioactive products in conjunction with optimized UAE is a promising contribution to the cosmetic industry that will help to strengthen the concept of environmentally-friendly “green chemistry”. Given that Carob pulp or seeds are considered food byproducts, the research presented here encourages the use of these agri-food waste materials in cosmetics