Health outcomes of only children across the life course : an investigation using Swedish register data

The proportion of only children – children with no full biological siblings – is growing in high-income settings, but we know little about their life course outcomes and how this is related to long-term health. Previous studies of only children have tended to focus on short-term, developmental and intellectual outcomes in early life or adolescence, and provide mixed evidence. Using Swedish population register data on children born between 1940 and 1975, we compare only children with children from multi-child sibling groups, taking into account birth order, family size and half-siblings to account for family complexity. We consider physical health outcomes measured at late adolescence (height, body mass index and physical fitness), and mortality. Only children with and without half-siblings had lower height and fitness scores, were more likely to be overweight or obese, and had higher mortality, than those with 1 or 2 biological siblings. Only children without half-siblings generally did better than only children with half-siblings, suggesting that only children experiencing parental disruption experience additional disadvantages. With the exception of height, the patterns persist after adjustment for parental characteristics and after employing within-family cousin comparison designs. In mortality models, some of the excess risk for only children was explained by adjustment for fertility, marriage and educational history. We discuss the extent to which the patterns we observe are explained by selection processes and contextual differences in the prevalence of one-child sibling groups.Publisher PD

Emulating the Wright State Model for Engineering Mathematics Education: Improving First-Year Engineering Student Retention

In 2004, Wright State University developed an innovative mathematics course for first-year engineering undergraduates in order to increase student retention, motivation and academic success. To date, the Wright State model has had a positive impact on student retention, motivation and academic success by increasing graduation rates and GPAs among participants. During the fall of 2014 and 2015, one large public university in the Midwest with more selective admission criteria decided to pilot a course based on the Wright State Model for Engineering Mathematics Education. Using the Wright State model, a mathematics for engineering course was offered to prospective students so they could subsequently begin engineering classes without a traditional calculus prerequisite. Each semester, a cohort of 31 first-year engineering students enrolled in the course. Instructors distributed surveys to students at the beginning and end of each term. In addition, university administrators tracked student grades in subsequent math and engineering courses. This paper will outline the details of the course as well as the academic performance and retention of these students. Preliminary findings suggest first to second year retention is higher with students who have taken the mathematics for engineering course. First-year students who take the course also earn higher grades in algebra, trigonometry, and introductory engineering courses, but not in Calculus I

A Traffic Analysis on Serverless Computing Based on the Example of a File Upload Stream on AWS Lambda

The shift towards microservisation which can be observed in recent developments of the cloud landscape for applications has led towards the emergence of the Function as a Service (FaaS) concept, also called Serverless. This term describes the event-driven, reactive programming paradigm of functional components in container instances, which are scaled, deployed, executed and billed by the cloud provider on demand. However, increasing reports of issues of Serverless services have shown significant obscurity regarding its reliability. In particular, developers and especially system administrators struggle with latency compliance. In this paper, following a systematic literature review, the performance indicators influencing traffic and the effective delivery of the provider’s underlying infrastructure are determined by carrying out empirical measurements based on the example of a File Upload Stream on Amazon’s Web Service Cloud. This popular example was used as an experimental baseline in this study, based on different incoming request rates. Different parameters were used to monitor and evaluate changes through the function’s logs. It has been found that the so-called Cold-Start, meaning the time to provide a new instance, can increase the Round-Trip-Time by 15%, on average. Cold-Start happens after an instance has not been called for around 15 min, or after around 2 h have passed, which marks the end of the instance’s lifetime. The research shows how the numbers have changed in comparison to earlier related work, as Serverless is a fast-growing field of development. Furthermore, emphasis is given towards future research to improve the technology, algorithms, and support for developers

OX133, a monoclonal antibody recognizing protein-bound N-ethylmaleimide for the identification of reduced disulfide bonds in proteins

In vivo, enzymatic reduction of some protein disulfide bonds, allosteric disulfide bonds, provides an important level of structural and functional regulation. The free cysteine residues generated can be labeled by maleimide reagents, including biotin derivatives, allowing the reduced protein to be detected or purified. During the screening of monoclonal antibodies for those specific for the reduced forms of proteins, we isolated OX133, a unique antibody that recognizes polypeptide resident, N-ethylmaleimide (NEM)-modified cysteine residues in a sequence-independent manner. OX133 offers an alternative to biotin-maleimide reagents for labeling reduced/alkylated antigens and capturing reduced/alkylated proteins with the advantage that NEM-modified proteins are more easily detected in mass spectrometry, and may be more easily recovered than is the case following capture with biotin based reagents

Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD): Exome sequencing of trios, monozygotic twins and tumours

BACKGROUND: Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is thought to be a genetic disease caused by de novo mutations, though causative mutations have yet to be identified. We searched for de novo coding mutations among a carefully-diagnosed and clinically homogeneous cohort of 35 ROHHAD patients. METHODS: We sequenced the exomes of seven ROHHAD trios, plus tumours from four of these patients and the unaffected monozygotic (MZ) twin of one (discovery cohort), to identify constitutional and somatic de novo sequence variants. We further analyzed this exome data to search for candidate genes under autosomal dominant and recessive models, and to identify structural variations. Candidate genes were tested by exome or Sanger sequencing in a replication cohort of 28 ROHHAD singletons. RESULTS: The analysis of the trio-based exomes found 13 de novo variants. However, no two patients had de novo variants in the same gene, and additional patient exomes and mutation analysis in the replication cohort did not provide strong genetic evidence to implicate any of these sequence variants in ROHHAD. Somatic comparisons revealed no coding differences between any blood and tumour samples, or between the two discordant MZ twins. Neither autosomal dominant nor recessive analysis yielded candidate genes for ROHHAD, and we did not identify any potentially causative structural variations. CONCLUSIONS: Clinical exome sequencing is highly unlikely to be a useful diagnostic test in patients with true ROHHAD. As ROHHAD has a high risk for fatality if not properly managed, it remains imperative to expand the search for non-exomic genetic risk factors, as well as to investigate other possible mechanisms of disease. In so doing, we will be able to confirm objectively the ROHHAD diagnosis and to contribute to our understanding of obesity, respiratory control, hypothalamic function, and autonomic regulation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13023-015-0314-x) contains supplementary material, which is available to authorized users

An Adequately Robust Early TNF-α Response Is a Hallmark of Survival Following Trauma/Hemorrhage

Background: Trauma/hemorrhagic shock (T/HS) results in cytokine-mediated acute inflammation that is generally considered detrimental. Methodology/Principal Findings: Paradoxically, plasma levels of the early inflammatory cytokine TNF-α (but not IL-6, IL-10, or NO2-/NO3-) were significantly elevated within 6 h post-admission in 19 human trauma survivors vs. 4 non-survivors. Moreover, plasma TNF-α was inversely correlated with Marshall Score, an index of organ dysfunction, both in the 23 patients taken together and in the survivor cohort. Accordingly, we hypothesized that if an early, robust pro-inflammatory response were to be a marker of an appropriate response to injury, then individuals exhibiting such a response would be predisposed to survive. We tested this hypothesis in swine subjected to various experimental paradigms of T/HS. Twenty-three anesthetized pigs were subjected to T/HS (12 HS-only and 11 HS + Thoracotomy; mean arterial pressure of 30 mmHg for 45-90 min) along with surgery-only controls. Plasma obtained at pre-surgery, baseline post-surgery, beginning of HS, and every 15 min thereafter until 75 min (in the HS only group) or 90 min (in the HS + Thoracotomy group) was assayed for TNF-α, IL-6, IL-10, and NO2-/NO3-. Mean post-surgery±HS TNF-α levels were significantly higher in the survivors vs. non-survivors, while non-survivors exhibited no measurable change in TNF-α levels over the same interval. Conclusions/Significance: Contrary to the current dogma, survival in the setting of severe, acute T/HS appears to be associated with an immediate increase in serum TNF-α. It is currently unclear if this response was the cause of this protection, a marker of survival, or both. This abstract won a Young Investigator Travel Award at the SHOCK 2008 meeting in Cologne, Germany. © 2009 Namas et al

Genomic screening of 16 UK native bat species through conservationist networks uncovers coronaviruses with zoonotic potential

There has been limited characterisation of bat-borne coronaviruses in Europe. Here, we screened for coronaviruses in 48 faecal samples from 16 of the 17 bat species breeding in the UK, collected through a bat rehabilitation and conservationist network. We recovered nine complete genomes, including two novel coronavirus species, across six bat species: four alphacoronaviruses, a MERS-related betacoronavirus, and four closely related sarbecoviruses. We demonstrate that at least one of these sarbecoviruses can bind and use the human ACE2 receptor for infecting human cells, albeit suboptimally. Additionally, the spike proteins of these sarbecoviruses possess an R-A-K-Q motif, which lies only one nucleotide mutation away from a furin cleavage site (FCS) that enhances infectivity in other coronaviruses, including SARS-CoV-2. However, mutating this motif to an FCS does not enable spike cleavage. Overall, while UK sarbecoviruses would require further molecular adaptations to infect humans, their zoonotic risk warrants closer surveillance

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology