Paternal and maternal influences on differences in birth weight between Europeans and Indians born in the UK.

BACKGROUND: Ethnic groups differ significantly in adult physique and birth weight. We aimed to improve understanding of maternal versus paternal contributions to ethnic differences in birth weight, by comparing the offspring of same-ethnic versus mixed-ethnic unions amongst Europeans and South Asian Indians in the UK. METHODOLOGY AND PRINCIPAL FINDINGS: We used data from the UK Office for National Statistics Longitudinal Study (LS) and the Chelsea and Westminster Hospital (CWH), London. In the combined sample at all gestational ages, average birth weight of offspring with two European parents was significantly greater than that of offspring with two Indian parents [Δ = 344 (95% CI 329, 360) g]. Compared to offspring of European mothers, the offspring of Indian mothers had lower birth weight, whether the father was European [Δ = -152 (95% CI -92, -212) g] or Indian [Δ = -254 (95% -315, -192) g]. After adjustment for various confounding factors, average birth weight of offspring with European father and Indian mother was greater than that of offspring with two Indian parents [LS: Δ = 249 (95% CI 143, 354) g; CWH: Δ = 236 (95% CI 62, 411) g]. Average birth weight of offspring with Indian father and European mother was significantly less than that of offspring with two European parents [LS: Δ = -117 (95% CI -207, -26) g; CWH: Δ = -83 (-206, 40) g]. CONCLUSIONS/SIGNIFICANCE: Birth weight of offspring with mixed-ethnic parentage was intermediate between that of offspring with two European or two Indian parents, demonstrating a paternal as well as a maternal contribution to ethnic differences in fetal growth. This can be interpreted as demonstrating paternal modulation of maternal investment in offspring. We suggest long-term nutritional experience over generations may drive such ethnic differences through parental co-adaptation

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy

The thymus is a central lymphoid organ with crucial role in generating T cells and maintaining homeostasis of the immune system. More than 30 peptides, initially referred to as “thymic hormones,” are produced by this gland. Although the majority of them have not been proven to be thymus-speciWc, thymic peptides comprise an eVective group of regulators, mediating important immune functions. Thymosin fraction Wve (TFV) was the Wrst thymic extract shown to stimulate lymphocyte proliferation and diVerentiation. Subsequent fractionation of TFV led to the isolation and characterization of a series of immunoactive peptides/polypeptides, members of the thymosin family. Extensive research on prothymosin (proT) and thymosin 1 (T1) showed that they are of clinical signiWcance and potential medical use. They may serve as molecular markers for cancer prognosis and/or as therapeutic agents for treating immunodeWciencies, autoimmune diseases and malignancies. Although the molecular mechanisms underlying their eVect are yet not fully elucidated proT and T1 could be considered as candidates for cancer immunotherapy. In this review, we will focus in principle on the eventual clinical utility of proT, both as a tumor biomarker and in triggering anticancer immune responses. Considering the experience acquired via the use of T1 to treat cancer patients, we will also discuss potential approaches for the future introduction of proT into the clinical setting

Epigenetics provides a new generation of oncogenes and tumour-suppressor genes

Cancer is nowadays recognised as a genetic and epigenetic disease. Much effort has been devoted in the last 30 years to the elucidation of the ‘classical' oncogenes and tumour-suppressor genes involved in malignant cell transformation. However, since the acceptance that major disruption of DNA methylation, histone modification and chromatin compartments are a common hallmark of human cancer, epigenetics has come to the fore in cancer research. One piece is still missing from the story: are the epigenetic genes themselves driving forces on the road to tumorigenesis? We are in the early stages of finding the answer, and the data are beginning to appear: knockout mice defective in DNA methyltransferases, methyl-CpG-binding proteins and histone methyltransferases strongly affect the risk of cancer onset; somatic mutations, homozygous deletions and methylation-associated silencing of histone acetyltransferases, histone methyltransferases and chromatin remodelling factors are being found in human tumours; and the first cancer-prone families arising from germline mutations in epigenetic genes, such as hSNF5/INI1, have been described. Even more importantly, all these ‘new' oncogenes and tumour-suppressor genes provide novel molecular targets for designed therapies, and the first DNA-demethylating agents and inhibitors of histone deacetylases are reaching the bedside of patients with haematological malignancies

Parapneumonic pleural effusion: early versus late thoracoscopy

ABSTRACT Objective: To evaluate the best time to perform thoracoscopy for the treatment of complicated parapneumonic pleural effusion in the fibrinopurulent phase in patients ≤ 14 years of age, regarding the postoperative evolution and occurrence of complications. Methods: This was a retrospective comparative study involving patients with parapneumonic pleural effusion presenting with septations or loculations on chest ultrasound who underwent thoracoscopy between January of 2000 and January of 2013. The patients were divided into two groups: early thoracoscopy (ET), performed by day 5 of hospitalization; and late thoracoscopy (LT), performed after day 5 of hospitalization. Results: We included 60 patients, 30 in each group. The mean age was 3.4 years; 28 patients (46.7%) were male; and 47 (78.3%) underwent primary thoracoscopy (no previous simple drainage). The two groups were similar regarding gender, age, weight, and type of thoracoscopy (p > 0.05 for all). There was a significant difference between the ET and the LT groups regarding the length of the hospital stay (14.5 days vs. 21.7 days; p < 0.001). There were also significant differences between the groups regarding the duration of fever in days; the total number of days from admission to the initiation of drainage; and the total number of days with the drain in place. Eight patients (13.6%) had at least one post-thoracoscopy complication, there being no difference between the groups. There were no deaths. Conclusions: Performing ET by day 5 of hospitalization was associated with shorter hospital stays, shorter duration of drainage, and shorter duration of fever, although not with a higher frequency of complications, requiring ICU admission, or requiring blood transfusion

Distinct cytokine profiles of circulating mononuclear cells stimulated with Staphylococcus aureus enterotoxin A in vitro during early and late episodes of chronic osteomyelitis

We investigated the cytokine profile of peripheral mononuclear cells from chronic osteomyelitis (OST) patients following in vitro stimulation with staphylococcal enterotoxin A (SEA). We demonstrate that stimulation with SEA induced prominent lymphocyte proliferation and high levels of tumour necrosis factor (TNF)-α, interleukin (IL)-4 and IL-10 secretion in both OST and non-infected individuals (NI). Even though stimulation with SEA had no impact on IL-6 production in either patient group, the baseline level of IL-6 production by cells from OST patients was always significantly less than that produced by cells from NI. After classifying the osteomyelitic episodes based on the time after the last reactivation event as "early" (1-4 months) or "late" osteomyelitis (5-12 months), we found that increased levels of TNF-α and IL-4 in combination with decreased levels of IL-6 were observed in the early episodes. By contrast, increased levels of IL-10, IL-2 and IL-6 were hallmarks of late episodes. Our data demonstrate that early osteomyelitic episodes are accompanied by an increased frequency of "high producers" of TNF-α and IL-4, whereas late events are characterised by increased frequencies of "high producers" of IL-10, IL-6 and IL-2. These findings demonstrate the distinct cytokine profiles in chronic osteomyelitis, with a distinct regulation of IL-6 production during early and late episodes

Designing an Optimal Kilonova Search Using DECam for Gravitational-wave Events

We address the problem of optimally identifying all kilonovae detected via gravitational-wave emission in the upcoming LIGO/Virgo/KAGRA observing run, O4, which is expected to be sensitive to a factor of ∼7 more binary neutron star (BNS) alerts than previously. Electromagnetic follow-up of all but the brightest of these new events will require >1 m telescopes, for which limited time is available. We present an optimized observing strategy for the DECam during O4. We base our study on simulations of gravitational-wave events expected for O4 and wide-prior kilonova simulations. We derive the detectabilities of events for realistic observing conditions. We optimize our strategy for confirming a kilonova while minimizing telescope time. For a wide range of kilonova parameters, corresponding to a fainter kilonova compared to GW170817/AT 2017gfo, we find that, with this optimal strategy, the discovery probability for electromagnetic counterparts with the DECam is ∼80% at the nominal BNS gravitational-wave detection limit for O4 (190 Mpc), which corresponds to an ∼30% improvement compared to the strategy adopted during the previous observing run. For more distant events (∼330 Mpc), we reach an ∼60% probability of detection, a factor of ∼2 increase. For a brighter kilonova model dominated by the blue component that reproduces the observations of GW170817/AT 2017gfo, we find that we can reach ∼90% probability of detection out to 330 Mpc, representing an increase of ∼20%, while also reducing the total telescope time required to follow up events by ∼20%