Glycolaldehyde formation via the dimerization of the formyl radical

Glycolaldehyde, the simplest monosaccharide sugar, has recently been detected in low- and high-mass star-forming cores. Following our previous investigation into glycolaldehyde formation, we now consider a further mechanism for the formation of glycolaldehyde that involves the dimerization of the formyl radical, HCO. Quantum mechanical investigation of the HCO dimerization process upon an ice surface is predicted to be barrierless and therefore fast. In an astrophysical context, we show that this mechanism can be very efficient in star-forming cores. It is limited by the availability of the formyl radical, but models suggest that only very small amounts of CO are required to be converted to HCO to meet the observational constraints

The cost-effectiveness of prophylaxis strategies for individuals with advanced HIV starting treatment in Africa

Introduction: Many HIV-positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced-prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4<100 cells/mm3. We investigated the cost-effectiveness of this enhanced-prophylaxis package versus other strategies, including using cryptococcal antigen (CrAg) testing, in individuals with CD4<200 cells/mm3 or <100 cells/mm3 at ART initiation and all individuals regardless of CD4 count. Methods: The REALITY trial enrolled from June 2013 to April 2015. A decision-analytic model was developed to estimate the cost-effectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standard-prophylaxis, enhanced-prophylaxis, standard-prophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhanced-prophylaxis (CrAg-positive) or standard-prophylaxis (CrAg-negative), the second to enhanced-prophylaxis (CrAg-positive) or enhanced-prophylaxis without fluconazole (CrAg-negative) and the third to standard-prophylaxis with fluconazole (CrAg-positive) or without fluconazole (CrAg-negative). The model estimated costs, life-years and quality-adjusted life-years (QALY) over 48 weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause. Results: Enhanced-prophylaxis was cost-effective at cost-effectiveness thresholds of US$300 and US$500 per QALY with an incremental cost-effectiveness ratio (ICER) of US$157 per QALY in the CD4<200 cells/mm3 population providing enhanced-prophylaxis components are sourced at lowest available prices. The ICER reduced in more severely immunosuppressed individuals (US$113 per QALY in the CD4<100 cells/mm3 population) and increased in all individuals regardless of CD4 count (US$722 per QALY). Results were sensitive to prices of the enhanced-prophylaxis components. Enhanced-prophylaxis was more effective and less costly than all CrAg testing strategies as enhanced-prophylaxis still conveyed health gains in CrAg-negative patients and savings from targeting prophylaxis based on CrAg status did not compensate for costs of CrAg testing. CrAg testing strategies did not become cost-effective unless the price of CrAg testing fell below US$2.30. Conclusions: The REALITY enhanced-prophylaxis package in individuals with advanced HIV starting ART reduces morbidity and mortality, is practical to administer and is cost-effective. Efforts should continue to ensure that components are accessed at lowest available prices. Funding REALITY was funded by the Joint Global Health Trials Scheme (JGHTS) of the UK Department for International Development (DFID), the Wellcome Trust and Medical Research Council (MRC)

Ice chemistry in massive Young Stellar Objects: the role of metallicity

We present the comparison of the three most important ice constituents (water, CO and CO2) in the envelopes of massive Young Stellar Objects (YSOs), in environments of different metallicities: the Galaxy, the Large Magellanic Cloud (LMC) and, for the first time, the Small Magellanic Cloud (SMC). We present observations of water, CO and CO2 ice in 4 SMC and 3 LMC YSOs (obtained with Spitzer-IRS and VLT/ISAAC). While water and CO2 ice are detected in all Magellanic YSOs, CO ice is not detected in the SMC objects. Both CO and CO2 ice abundances are enhanced in the LMC when compared to high-luminosity Galactic YSOs. Based on the fact that both species appear to be enhanced in a consistent way, this effect is unlikely to be the result of enhanced CO2 production in hotter YSO envelopes as previously thought. Instead we propose that this results from a reduced water column density in the envelopes of LMC YSOs, a direct consequence of both the stronger UV radiation field and the reduced dust-to-gas ratio at lower metallicity. In the SMC the environmental conditions are harsher, and we observe a reduction in CO2 column density. Furthermore, the low gas-phase CO density and higher dust temperature in YSO envelopes in the SMC seem to inhibit CO freeze-out. The scenario we propose can be tested with further observations.Comment: accepted by MNRAS Letters; 5 pages, 3 figures, 1 tabl

Neuroimaging young children and associations with neurocognitive development in a South African birth cohort study.

Magnetic resonance imaging (MRI) is an indispensable tool for investigating brain development in young children and the neurobiological mechanisms underlying developmental risk and resilience. Sub-Saharan Africa has the highest proportion of children at risk of developmental delay worldwide, yet in this region there is very limited neuroimaging research focusing on the neurobiology of such impairment. Furthermore, paediatric MRI imaging is challenging in any setting due to motion sensitivity. Although sedation and anesthesia are routinely used in clinical practice to minimise movement in young children, this may not be ethical in the context of research. Our study aimed to investigate the feasibility of paediatric multimodal MRI at age 2-3 years without sedation, and to explore the relationship between cortical structure and neurocognitive development at this understudied age in a sub-Saharan African setting. A total of 239 children from the Drakenstein Child Health Study, a large observational South African birth cohort, were recruited for neuroimaging at 2-3 years of age. Scans were conducted during natural sleep utilising locally developed techniques. T1-MEMPRAGE and T2-weighted structural imaging, resting state functional MRI, diffusion tensor imaging and magnetic resonance spectroscopy sequences were included. Child neurodevelopment was assessed using the Bayley-III Scales of Infant and Toddler Development. Following 23 pilot scans, 216 children underwent scanning and T1-weighted images were obtained from 167/216 (77%) of children (median age 34.8 months). Furthermore, we found cortical surface area and thickness within frontal regions were associated with cognitive development, and in temporal and frontal regions with language development (beta coefficient ?0.20). Overall, we demonstrate the feasibility of carrying out a neuroimaging study of young children during natural sleep in sub-Saharan Africa. Our findings indicate that dynamic morphological changes in heteromodal association regions are associated with cognitive and language development at this young age. These proof-of-concept analyses suggest similar links between the brain and cognition as prior literature from high income countries, enhancing understanding of the interplay between cortical structure and function during brain maturation

Sustaining entrepreneurial business: a complexity perspective on processes that produce emergent practice

This article examines the management practices in an entrepreneurial small firm which sustain the business. Using a longitudinal qualitative case study, four general processes are identified (experimentation, reflexivity, organising and sensing), that together provide a mechanism to sustain the enterprise. The analysis draws on concepts from entrepreneurship and complexity science. We suggest that an entrepreneur’s awareness of the role of these parallel processes will facilitate their approaches to sustaining and developing enterprises. We also suggest that these processes operate in parallel at multiple levels, including the self, the business and inter-firm networks. This finding contributes to a general theory of entrepreneurship. A number of areas for further research are discussed arising from this result

Phase II trial of standard versus increased transfusion volume in Ugandan children with acute severe anemia.

BACKGROUND: Severe anemia (SA, hemoglobin 6 g/dl: primary outcome) and 28-day survival. RESULTS: Median admission hemoglobin was 4.2 g/dl (IQR 3.1 to 4.9). Initial volume received followed the randomization strategy in 155 (97%) patients. By 24-hours, 70 (90%) children in the Tx30 arm had corrected SA compared to 61 (74%) in the Tx20 arm; cause-specific hazard ratio = 1.54 (95% confidence interval 1.09 to 2.18, P = 0.01). From admission to day 28 there was a greater hemoglobin increase from enrollment in Tx30 (global P <0.0001). Serious adverse events included one non-fatal allergic reaction and one death in the Tx30 arm. There were six deaths in the Tx20 arm (P = 0.12); three deaths were adjudicated as possibly related to transfusion, but none secondary to volume overload. CONCLUSION: A higher initial transfusion volume prescribed at hospital admission was safe and resulted in an accelerated hematological recovery in Ugandan children with SA. Future testing in a large, pragmatic clinical trial to establish the effect on short and longer-term survival is warranted. TRIAL REGISTRATION: ClinicalTrials.Gov identifier: NCT01461590 registered 26 October 2011

Flash monitor initiation is associated with improvements in HbA1c levels and DKA rates among people with Type 1 Diabetes in Scotland:a retrospective nationwide observational study

Funding Information: This study was supported by funding from the Diabetes UK (17/0005627) and the Chief Scientist Office (Ref. ETM/47).Peer reviewedPublisher PD

Marked improvements in glycaemic outcomes following insulin pump therapy initiation in people with type 1 diabetes:a nationwide observational study in Scotland

This study was supported by funding from Diabetes UK (17/0005627) and the Chief Scientist Office (ref. ETM/47).Aims/hypothesis Our aim was to assess the use of continuous subcutaneous insulin infusion (CSII) in people with type 1 diabetes in Scotland and its association with glycaemic control, as measured by HbA1c levels, frequency of diabetic ketoacidosis (DKA) and severe hospitalised hypoglycaemia (SHH), overall and stratified by baseline HbA1c. Methods We included 4684 individuals with type 1 diabetes from the national Scottish register, who commenced CSII between 2004 and 2019. We presented crude within-person differences from baseline HbA1c over time since initiation, crude DKA and SHH event-rates pre-/post-CSII exposure. We then used mixed models to assess the significance of CSII exposure, taking into account: (1) the diffuse nature of the intervention (i.e. structured education often precedes initiation); (2) repeated within-person measurements; and (3) background time-trends occurring pre-intervention. Results HbA1c decreased after CSII initiation, with a median within-person change of −5.5 mmol/mol (IQR −12.0, 0.0) (−0.5% [IQR −1.1, 0.0]). Within-person changes were most substantial in those with the highest baseline HbA1c, with median −21.0 mmol/mol (−30.0, −11.0) (−1.9% [−2.7, −1.0]) change in those with a baseline >84 mmol/mol (9.8%) within a year of exposure, that was sustained: −19.0 mmol/mol (−27.6, −6.5) (−1.7% [−2.5, −0.6]) at ≥5 years. Statistical significance and magnitude of change were supported by the mixed models results. The crude DKA event-rate was significantly lower in post-CSII person-time compared with pre-CSII person-time: 49.6 events (95% CI 46.3, 53.1) per 1000 person-years vs 67.9 (64.1, 71.9); rate ratio from Bayesian mixed models adjusting for pre-exposure trend: 0.61 (95% credible interval [CrI] 0.47, 0.77; posterior probability of reduction pp = 1.00). The crude overall SHH event-rate in post-CSII vs pre-CSII person-time was also lower: 17.8 events (95% CI 15.8, 19.9) per 1000 person-years post-exposure vs 25.8 (23.5, 28.3) pre-exposure; rate ratio from Bayesian mixed models adjusting for pre-exposure trend: 0.67 (95% CrI 0.45, 1.01; pp = 0.97). Conclusions/interpretation CSII therapy was associated with marked falls in HbA1c especially in those with high baseline HbA1c. CSII was independently associated with reduced DKA and SHH rates. CSII appears to be an effective option for intensive insulin therapy in people with diabetes for improving suboptimal glycaemic control.Publisher PDFPeer reviewe

Disentangling a group of lensed submm galaxies at z∼ 2.9

MS0451.6−0305 is a rich galaxy cluster whose strong lensing is particularly prominent at submm wavelengths. We combine new Submillimetre Common-User Bolometer Array (SCUBA)-2 data with imaging from Herschel Spectral and Photometric Imaging Receiver (SPIRE) and PACS and Hubble Space Telescope in order to try to understand the nature of the sources being lensed. In the region of the ‘giant submm arc', we uncover seven multiply imaged galaxies (up from the previously known four), of which six are found to be at a redshift of z∼2.9, and possibly constitute an interacting system. Using a novel forward-modelling approach, we are able to simultaneously deblend and fit spectral energy distributions to the individual galaxies that contribute to the giant submm arc, constraining their dust temperatures, far-infrared luminosities, and star formation rates (SFRs). The submm arc first identified by SCUBA can now be seen to be composed of at least five distinct sources, four of these within a galaxy group at z∼2.9. Only a handful of lensed galaxy groups at this redshift are expected on the sky, and thus this is a unique opportunity for studying such systems in detail. The total unlensed luminosity for this galaxy group is (3.1±0.3)×1012 L⊙, which gives an unlensed SFR of (450±50) M⊙yr−1. This finding suggests that submm source multiplicity, due to physically associated groupings as opposed to chance alignment, extends to fainter flux densities than previously discovered. Many of these systems may also host optical companions undetected in the submm, as is the case her

Rising Rates And Widening Socio-economic Disparities In Diabetic Ketoacidosis In Type 1 Diabetes In Scotland:A Nationwide Retrospective Cohort Observational Study

OBJECTIVE: Whether advances in the management of type 1 diabetes are reducing rates of diabetic ketoacidosis (DKA) is unclear. We investigated time trends in DKA rates in a national cohort of individuals with type 1 diabetes monitored for 14 years, overall and by socioeconomic characteristics. RESEARCH DESIGN AND METHODS: All individuals in Scotland with type 1 diabetes who were alive and at least 1 year old between 1 January 2004 and 31 December 2018 were identified using the national register (N 5 37,939). DKA deaths and hospital admissions were obtained through linkage to Scottish national death and morbidity records. Bayesian regression was used to test for DKA time trends and association with risk markers, including socioeconomic deprivation. RESULTS: There were 30,427 DKA admissions and 472 DKA deaths observed over 393,223 person-years at risk. DKA event rates increased over the study period (incidence rate ratio [IRR] per year 1.058 [95% credibility interval 1.054–1.061]). Males had lower rates than females (IRR male-to-female 0.814 [0.776–0.855]). DKA incidence rose in all age-groups other than 10- to 19-year-olds, in whom rates were the highest, but fell over the study. There was a large socioeconomic differential (IRR least-to-most deprived quintile 0.446 [0.406–0.490]), which increased during follow-up. Insulin pump use or completion of structured education were associated with lower DKA rates, and antidepressant and methadone prescription were associated with higher DKA rates. CONCLUSIONS: DKA incidence has risen since 2004, except in 10- to 19-year-olds. Of particular concern are the strong and widening socioeconomic disparities in DKA outcomes. Efforts to prevent DKA, especially in vulnerable groups, require strengthening