Gas and star formation from HD and dust emission in a strongly lensed galaxy

The molecular gas content of high-redshift galaxies is a highly sought-after property. However, H$_2$ is not directly observable in most environments, so its mass is probed through other emission lines (e.g., CO, [CI], [CII]), or through a gas-to-dust ratio. Each of these methods depends on several assumptions, and are best used in parallel. In this work, we extend an additional molecular gas tracer to high-redshift studies by observing hydrogen deuteride (HD) emission in the strongly lensed $z=5.656$ galaxy SPT0346-52 with ALMA. While no HD(1-0) emission is detected, we are able to place an upper limit on the gas mass of $\rm M_{H_2}<6.4\times10^{11} M_{\odot}$. This is used to find a limit on the $\rm L'_{CO}$ conversion factor of $\rm\alpha_{CO}<5.8$ M$_{\odot}$(K km s$^{-1}$ pc$^2$)$^{-1}$. In addition, we construct the most complete spectral energy distribution (SED) of this source to date, and fit it with a single-temperature modified blackbody using the nested sampling code MultiNest, yielding a best-fit dust mass $\rm M_{dust}=10^{8.92\pm0.02}$ M$_{\odot}$, dust temperature $78.6\pm0.5$ K, dust emissivity spectral index $\beta=1.81\pm0.03$, and star formation rate $\rm SFR=3800\pm100$ M$_{\odot}$ year$^{-1}$. Using the continuum flux densities to estimate the total gas mass of the source, we find $\rm M_{H_2}<2.4\times10^{11}$ M$_{\odot}$, assuming sub-solar metallicity. This implies a CO conversion factor of $\rm \alpha_{CO}<2.2$, which is between the standard values for MW-like galaxies and starbursts. These properties confirm that SPT0346-52 is a heavily starbursting, gas rich galaxy.STFC ER

Detection of a high-redshift molecular outflow in a primeval hyperstarburst galaxy

We report the discovery of a high-redshift, massive molecular outflow in the starburst galaxy SPT0346-52 (z = 5:656) via the detected absorption of high-excitation water transitions (H2O 42;3 41;4 and H2O 33;0 32;1) with the Atacama Large Millimeter/ submillimeter Array (ALMA). The host galaxy is one of the most powerful starburst galaxies at high redshift (star formation rate; SFR ~ 3,600M $_{\odot}$ year{^{-}}1), with an extremely compact (~ 320 pc) star formation region and a star formation rate surface density ($\Sigma$SFR ~ 5; 500M$_{\odot}$ year{^{-}}1 kpc{^{-}}2) five times higher than ‘maximum’ (i.e. Eddington-limited) starbursts, implying a highly transient phase. The estimated outflow rate is ~ 500M$_{\odot}$ year{^{-}}1, which is much lower than the SFR, implying that in this extreme starburst the outflow capabilities saturate and the outflow is no longer capable of regulating star formation, resulting in a runaway process in which star formation will use up all available gas in less than 30 Myr. Finally, while previous kinematic investigations of this source revealed possible evidence for an ongoing major merger, the coincidence of the hyper-compact starburst and high-excitation water absorption indicates that this is a single starburst galaxy surrounded by a disc.Includes STFC and ERC

Path dependence in energy systems and economic development

Energy systems are subject to strong and long-lived path dependence, owing to technological, infrastructural, institutional and behavioural lock-ins. Yet, with the prospect of providing accessible cheap energy to stimulate economic development and reduce poverty, governments often invest in large engineering projects and subsidy policies. Here, I argue that while these may achieve their objectives, they risk locking their economies onto energy-intensive pathways. Thus, particularly when economies are industrializing, and their energy systems are being transformed and are not yet fully locked-in, policymakers should take care before directing their economies onto energy-intensive pathways that are likely to be detrimental to their long-run prosperity

Alzheimer's Disease susceptibility genes APOE and TOMM40, and hippocampal volumes in the Lothian birth cohort 1936

The APOE ε and TOMM40 rs10524523 (‘523’) variable length poly-T repeat gene loci have been significantly and independently associated with Alzheimer’s disease (AD) related phenotypes such as age of clinical onset. Hippocampal atrophy has been significantly associated with memory impairment, a characteristic of AD. The current study aimed to test for independent effects of APOE ε and TOMM40 ‘523’ genotypes on hippocampal volumes as assessed by brain structural MRI in a relatively large sample of community-dwelling older adults. As part of a longitudinal study of cognitive ageing, participants in the Lothian Birth Cohort 1936 underwent genotyping for APOE ε2/ε3/ε4 status and TOMM40 ‘523’ poly-T repeat length, and detailed structural brain MRI at a mean age of 72.7 years (standard deviation = 0.7, N range = 624 to 636). No significant effects of APOE ε or TOMM40 523 genotype were found on hippocampal volumes when analysed raw, or when adjusted for either intracranial or total brain tissue volumes. In summary, in a large community-dwelling sample of older adults, we found no effects of APOE ε or TOMM40 523 genotypes on hippocampal volumes. This is discrepant with some previous reports of significant association between APOE and left/right hippocampal volumes, and instead echoes other reports that found no association. Previous significant findings may partly reflect type 1 error. Future studies should carefully consider: 1) their specific techniques in adjusting for brain size; 2) assessing more detailed sub-divisions of the hippocampal formation; and 3) testing whether significant APOE-hippocampal associations are independent of generalised brain atrophy

Once versus twice daily administration of didanosine in children with symptomatic HIV-associated disease who were intolerant to or clinically deteriorated on zidovudine. The Italian Pediatric Collaborative Study Group on Didanosine.

The objective of this study was to compare the safety, tolerability and clinical response of once- versus twice-daily administration of didanosine given at a dosage of 270 mg/m2/day in children with symptomatic HIV-associated disease who were intolerant to or clinically deteriorated on zidovudine monotherapy. We carried out a randomized, open-label multicentre trial. Didanosine was supplied in buffered tablets, which could be chewed or dispersed in liquid. The children were recruited from 16 paediatric departments participating in the Italian Register for HIV Infection in Children. A total of 53 children (median age 5.5 years) started trial treatment; 26 were given didanosine twice daily and 27 once daily; 85% had AIDS and 98% had clinically deteriorated while on zidovudine therapy. Similar safety and tolerability results were demonstrated for the two schemes of therapy. A total of 11 children (20.7%) required discontinuation of didanosine for severe adverse events (five children (19.2%) in the twice-daily group; six children (22.2%) in the once-daily group, log-rank P = 0.81). Severe hepatic toxicity was uncommon (5.6%) while mild to moderate hepatic dysfunction was demonstrated in about 17% of the participants, without any difference between the two groups. Haematological toxicity was common (about 40% of the children, 11 in the twice- and 19 in the once-daily group) but never severe. Clinical pancreatitis and retinal lesions were never demonstrated. There was no significant difference in progression to death or to a new opportunistic infection between the two treatment regimens (log-rank P = 0.54). The modification of surrogate efficacy parameters during the study period was similar in the two groups. However, weight gain was poorer in children treated once daily. This study suggests that the safety and tolerability of 270 mg/m2/day of didanosine given once daily is substantially similar to that of the traditionally recommended schedule of two divided doses. Owing to the small sample and to the severity of the clinical condition of the children enrolled, no definite conclusions on the comparative efficacy of the two regimens can be drawn

Long-term administration of aerosolized pentamidine as primary prophylaxis against Pneumocystis carinii pneumonia in infants and children with symptomatic human immunodeficiency virus infection

We assessed the long-term feasibility, safety, and tolerability of two regimens of aerosolized pentamidine (AP) as primary prophylaxis of Pneumocystis carinii pneumonia (PCP) in a large sample of infants and children with symptomatic HIV infection in 21 pediatric departments. One hundred forty children were assigned to receive 60 mg every 2 weeks (n = 60) or 120 mg every 4 weeks (n = 80) of AP, delivered by the ultrasonic nebulizer Fisoneb under the supervision of trained personnel. Children underwent monthly clinical and laboratory controls for toxicity and/or development of PCP for an 18-month period. Baseline characteristics were similar in the two treatment groups. The median age was 5 years. The feasibility of administering AP was excellent in 84 (60%) and good in 38 (27%) children, All children aged <2 years showed excellent or good feasibility. Long-term compliance was good with both regimens. No child had severe adverse reactions requiring discontinuation of the treatment. Cough, sneezing, and bronchospasm were the most frequent side effects occurring, respectively, in 12, 3.7, and 0.7% of the 60-mg treatments and in 19.1, 6.1, and 2.8% of 120-mg treatments (p < 0.05). Their incidence was not different in children younger or older than 5 years. Two episodes of PCP were observed in the group receiving 120 mg monthly, whereas none of the 60 children in the biweekly schedule had PCP (p = 0.20), AP can be safely administered to very young children with few adverse effects

Long-term administration of aerosolized pentamidine as primary prophylaxis against Pneumocystis carinii pneumonia in infants and children with symptomatic human immunodeficiency virus infection. The Italian Pediatric Collaborative Study Group on Pentamidine.

SUMMARY: We assessed the long-term feasibility, safety, and tolerability of two regimens of aerosolized pentamidine (AP) as primary prophylaxis of Pneumocystis carinii pneumonia (PCP) in a large sample of infants and children with symptomatic HIV infection in 21 pediatric departments. One hundred forty children were assigned to receive 60 mg every 2 weeks (n = 60) or 120 mg every 4 weeks (n = 80) of AP, delivered by the ultrasonic nebulizer Fisoneb under the supervision of trained personnel. Children underwent monthly clinical and laboratory controls for toxicity and/or development of PCP for an 18-month period. Baseline characteristics were similar in the two treatment groups. The median age was 5 years. The feasibility of administering AP was excellent in 84 (60 percent) and good in 38 (27 percent) children. All children aged <2 years showed excellent or good feasibility. Long-term compliance was good with both regimens. No child had severe adverse reactions requiring discontinuation of the treatment. Cough, sneezing, and bronchospasm were the most frequent side effects occurring, respectively, in 12, 3.7, and 0.7 percent of the 60-mg treatments and in 19.1, 6. 1, and 2.8 percent of 120-mg treatments (p < 0.05). Their incidence was not different in children younger or older than 5 years. Two episodes of PCP were observed in the group receiving 120 mg monthly, whereas none of the 60 children in the biweekly schedule had PCP (p = 0.20). AP can be safely administered to very young children with few adverse side effects

ONSET OF CLINICAL SIGNS IN CHILDREN WITH HIV-1 PERINATAL INFECTION

Objective: To investigate the timing of onset of each clinical sign in infants and children with HIV-1 perinatal infection. Design and methods: A total of 200 HIV-l-infected children followed-up from birth were studied. Failure and conditional probabilities were estimated by the Kaplan-Meier product-limit method. Cox proportional hazard analysis was used to evaluate independently associated factors. Results of 934 seroreverters were used to calculate reference values of CD4+ cell counts and predictivity of early signs. Results: Median age at the onset of any sign was 5.2 months (range, 0.03-56 months). The probability of remaining asymptomatic was 19% [95% confidence interval (CI), 14-25.1] at 12 months and 6.1% (95% CI, 2.6-11.7) at 5 years. Lymphadenopathy (69.5%), splenomegaly (62.4%) and hepatomegaly (58.4%) were the most common signs in the first year of life. Peculiar to the first year of life (compared with subsequent ages) was the onset of primary HIV-1 hepatitis and diarrhoea (rate ratios, 23.3 and 15.2, respectively). When CD4+ cell counts in the asymptomatic stage (age, 2 months; range, 0.03-5.9 months) were below rather than above the fifth percentile in seroreverters, onset of signs was earlier [3 (range, 0.03-19) versus 5 (range, 0.03-56) months]. Children manifesting signs before the 5.2-month breakpoint had a lower survival rate [74% (range, 65.9-82%) at 12 months and 45% (range, 32.9-57%) at 5 years] than children manifesting signs later [98% (range, 92.2-100%) at 12 months and 74% (range, 60.3-87.7%) at 5 years]. Children whose birthweight was less than or equal to 2400 g had an earlier onset (24 months; range, 1-57 months) of severe conditions than children with higher birthweight (71 months; range, 1-71 months). Development of lymphadenopathy or hepatosplenomegaly within 3 months of life were reliable indicators of infection. Conclusions: This study describes the sequence of onset of signs in perinatal HIV-1 infection. Infection is shown to progress faster than in adults and in a different manner. Low birthweight, early decreased CD4+ cell counts, and early onset of signs are predictive of rapid progression