The identification of high-redshift, massive galaxies with old stellar populations may pose challenges to some models of galaxy formation. However, to securely classify a galaxy as quiescent, it is ...necessary to exclude significant ongoing star formation, something that can be challenging to achieve at high redshifts. In this Letter, we analyze deep ALMA/870 m and SCUBA-2/450 m imaging of the claimed "post-starburst" galaxy ZF 20115 at z = 3.717 that exhibits a strong Balmer break and absorption lines. The rest-frame far-infrared imaging identifies a luminous starburst 0 4 0 1 (∼3 kpc in projection) from the position of the ultraviolet/optical emission and is consistent with lying at the redshift of ZF 20115. The star-forming component, with an obscured star formation rate of , is undetected in the rest-frame ultraviolet but contributes significantly to the lower angular resolution photometry at rest-frame wavelengths 3500 . This contribution from the obscured starburst, especially in the Spitzer/IRAC wavebands, significantly complicates the determination of a reliable stellar mass for the ZF 20015 system, and we conclude that this source does not pose a challenge to current models of galaxy formation. The multi-wavelength observations of ZF 20115 unveil a complex system with an intricate and spatially varying star formation history. ZF 20115 demonstrates that understanding high-redshift obscured starbursts will only be possible with multi-wavelength studies that include high-resolution observations, available with the James Webb Space Telescope, at mid-infrared wavelengths.
In this study, we undertook a randomized phase III trial of 105 NSCLC patients with oligo (one to four) -brain metastases. Patients were randomly assigned (1:1) to receive either stereotactic ...radiosurgery (SRS) followed by chemotherapy or upfront chemotherapy alone. The results demonstrated that SRS followed by chemotherapy did not improve overall survival compared with upfront chemotherapy only.
It is unclear whether treating brain metastasis before starting systemic chemotherapy can improve survival compared with upfront chemotherapy in non-small-cell lung cancer (NSCLC) with asymptomatic cerebral oligo-metastases.
We undertook a randomized, controlled trial of 105 patients with one to four brain metastases, admitted to Samsung Medical Center between 2008 and 2013. Patients were randomly assigned to receive stereotactic radiosurgery (SRS) (49 patients) followed by chemotherapy or upfront chemotherapy (49 patients). The primary end point was overall survival (OS) and secondary end points included central nervous system (CNS) progression-free survival, progression to symptomatic brain metastasis and brain functional outcome.
The median age was 58 years (range, 29–85) with ECOG 0–1 performance status, and 40% of patients were never smokers. Most patients had adenocarcinoma, and about half of patients had only one brain metastasis, while the rest had multiple cerebral metastases. The median OS time was 14.6 months 95% confidence interval (CI), 9.2–20.0 in the SRS group and 15.3 months (95% CI, 7.2–23.4) for the upfront chemotherapy group (P = 0.418). There was no significant difference in time to CNS disease progression median, 9.4 months (SRS) versus 6.6 months (upfront chemotherapy),P = 0.248. Symptomatic progression of brain metastases was observed more frequently in the upfront chemotherapy group (26.5%) than the SRS group (18.4%) but without statistical significance.
Although this study included smaller sample size than initially anticipated due to early termination, SRS followed by chemotherapy did not improve OS in oligo-brain metastases NSCLC patients compared with upfront chemotherapy. Further study with large number of patients should be needed to confirm the use of upfront chemotherapy alone in this subgroup of patients.
NCT01301560.
Background
Microbial colonization of the airway plays a role in the pathogenesis of asthma; however, the effect of the upper airway microbiome on childhood asthma is not fully understood. We analyzed ...the metagenome of airway microbiome to understand the associated role of upper airway microbiome with the natural course of childhood asthma.
Methods
Nasopharyngeal swabs were collected from children with asthma, those in asthma remission, and control groups. High‐throughput sequencing was used to examine the structure and functional dynamics of the airway microbiome with respect to asthma phenotypes.
Results
The composition of microbiota differed among healthy control, asthma, and remission groups. The relative abundance of Streptococcus was negatively associated with FEV1% predicted (P = .023) and that of Staphylococcus was negatively associated with methacholine PC20 (P = .013). Genes related to arachidonic acid metabolites, lysine residues, and glycosaminoglycans in the microbiome could be associated with airway inflammation. In particular, genes related to synthesis of anti‐inflammatory prostaglandin E2 (PGE2) were not detected from the airway microbiome in the asthma group.
Conclusions
These data suggest that alterations in the composition and function of the upper airway microbiome could be related with the natural course of asthma in children.
The antiferroelectricity in HfZrO 2 (HZO) annealed at 600 °C with an abrupt turn ON of FET characteristics with SSmin = 23 mV/dec and SSavg = 50 mV/dec over 4 decades of IDS is demonstrated. The near ...non-hysteresis is achieved with an antiferroelectric-like HZO due to a small remanent polarization and a coercive field. A feasible concept of coupling the antiferroelectric and ferroelectric type HZO are used for low-power electronics and the memory applications, respectively.
Summary
Background
Little is known about factors affecting the quality of life (QoL) of patients with vitiligo, and previous studies have shown conflicting results.
Objectives
To explore the QoL of ...patients with vitiligo and to identify factors affecting QoL.
Methods
A nationwide questionnaire‐based study was conducted with 1123 patients with vitiligo recruited from 21 hospitals in Korea from July 2015 to June 2016. Data were collected using a structured questionnaire for demographic information and the Skindex‐29 instrument. Mild or severely impaired QoL in patients with vitiligo was assessed according to each domain (symptoms, functioning and emotions) of Skindex‐29. Multivariate logistic regression analyses were performed to determine the factors associated with QoL.
Results
Of the enrolled participants, 609 were male and 514 female, with a mean age of 49·8 years (range 20–84). The median duration of disease was 3·0 years (range 0–60). Using multivariate logistic regression modelling, the involvement of visible body parts and a larger affected body surface area were consistently associated with QoL impairment in all three domains of Skindex‐29. Additionally, the QoL of patients aged 20–59 years, who potentially had a more active social life than older patients, was associated with functional impairment. Furthermore, a higher educational background was associated with emotional impairment.
Conclusions
A multitude of factors significantly influence the QoL of patients with vitiligo. A better appreciation of these factors would help the management of these patients.
What's already known about this topic?
Quality of life is highly impaired in patients with vitiligo.
What does this study add?
The involvement of visible body parts and a larger affected body surface area were consistently associated with impaired symptoms, functioning and emotions.
Vitiligo with nonvisible lesions also considerably compromises quality of life; vitiligo should not be regarded as a cosmetic problem.
Patients aged 20–59 years experienced significant functional impairment, and those with a higher educational background had more impairment in their emotions.
Linked Comment: Ezzedine and Eleftheriadou. Br J Dermatol 2018; 178:28–29.
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There is emerging literature demonstrating a relationship between the timing of feeding and weight regulation in animals. However, whether the timing of food intake influences the success of a ...weight-loss diet in humans is unknown.
To evaluate the role of food timing in weight-loss effectiveness in a sample of 420 individuals who followed a 20-week weight-loss treatment.
Participants (49.5% female subjects; age (mean ± s.d.): 42 ± 11 years; BMI: 31.4 ± 5.4 kg m(-2)) were grouped in early eaters and late eaters, according to the timing of the main meal (lunch in this Mediterranean population). 51% of the subjects were early eaters and 49% were late eaters (lunch time before and after 1500 hours, respectively), energy intake and expenditure, appetite hormones, CLOCK genotype, sleep duration and chronotype were studied.
Late lunch eaters lost less weight and displayed a slower weight-loss rate during the 20 weeks of treatment than early eaters (P=0.002). Surprisingly, energy intake, dietary composition, estimated energy expenditure, appetite hormones and sleep duration was similar between both groups. Nevertheless, late eaters were more evening types, had less energetic breakfasts and skipped breakfast more frequently that early eaters (all; P<0.05). CLOCK rs4580704 single nucleotide polymorphism (SNP) associated with the timing of the main meal (P=0.015) with a higher frequency of minor allele (C) carriers among the late eaters (P=0.041). Neither sleep duration, nor CLOCK SNPs or morning/evening chronotype was independently associated with weight loss (all; P>0.05).
Eating late may influence the success of weight-loss therapy. Novel therapeutic strategies should incorporate not only the caloric intake and macronutrient distribution - as is classically done - but also the timing of food.
For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, ...an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin “burn propagation” into surrounding cold fuel, enabling the possibility of high energy gain. While “scientific breakeven” (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this work reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion.
Tooth enamel is the most highly mineralized tissue in vertebrates. Enamel crystal formation and elongation should be well controlled to achieve an exceptional hardness and a compact microstructure. ...Enamel matrix calcification occurs with several matrix proteins, such as amelogenin, enamelin, and ameloblastin. Among them, amelogenin is the most abundant enamel matrix protein, and multiple isoforms resulting from extensive but well-conserved alternative splicing and postsecretional processing have been identified. In this report, we recruited a family with a unique enamel defect and identified a silent mutation in exon 4 of the AMELX gene. We show that the mutation caused the inclusion of exon 4, which is almost always skipped, in the mRNA transcript. We further show, by generating and characterizing a transgenic animal model, that the alteration of the ratio and quantity of the developmentally conserved alternative splicing repertoire of AMELX caused defects in enamel matrix mineralization.
Summary Background The effects of malaria and its treatment in the first trimester of pregnancy remain an area of concern. We aimed to assess the outcome of malaria-exposed and malaria-unexposed ...first-trimester pregnancies of women from the Thai–Burmese border and compare outcomes after chloroquine-based, quinine-based, or artemisinin-based treatments. Methods We analysed all antenatal records of women in the first trimester of pregnancy attending Shoklo Malaria Research Unit antenatal clinics from May 12, 1986, to Oct 31, 2010. Women without malaria in pregnancy were compared with those who had a single episode of malaria in the first trimester. The association between malaria and miscarriage was estimated using multivariable logistic regression. Findings Of 48 426 pregnant women, 17 613 (36%) met the inclusion criteria: 16 668 (95%) had no malaria during the pregnancy and 945 (5%) had a single episode in the first trimester. The odds of miscarriage increased in women with asymptomatic malaria (adjusted odds ratio 2·70, 95% CI 2·04–3·59) and symptomatic malaria (3·99, 3·10–5·13), and were similar for Plasmodium falciparum and Plasmodium vivax . Other risk factors for miscarriage included smoking, maternal age, previous miscarriage, and non-malaria febrile illness. In women with malaria, additional risk factors for miscarriage included severe or hyperparasitaemic malaria (adjusted odds ratio 3·63, 95% CI 1·15–11·46) and parasitaemia (1·49, 1·25–1·78 for each ten-fold increase in parasitaemia). Higher gestational age at the time of infection was protective (adjusted odds ratio 0·86, 95% CI 0·81–0·91). The risk of miscarriage was similar for women treated with chloroquine (92 26% of 354), quinine (95 27%) of 355), or artesunate (20 31% of 64; p=0·71). Adverse effects related to antimalarial treatment were not observed. Interpretation A single episode of falciparum or vivax malaria in the first trimester of pregnancy can cause miscarriage. No additional toxic effects associated with artesunate treatment occurred in early pregnancy. Prospective studies should now be done to assess the safety and efficacy of artemisinin combination treatments in early pregnancy. Funding Wellcome Trust and Bill & Melinda Gates Foundation.
Immune checkpoint inhibitors (ICIs) have been shown to be beneficial for some patients with advanced non-small-cell lung cancer (NSCLC). However, the underlying mechanisms mediating the limited ...response to ICIs remain unclear.
We carried out whole-exome sequencing on 198 advanced NSCLC tumors that had been sampled before anti-programmed cell death 1 (anti-PD-1)/programmed death-ligand 1 (PD-L1) therapy. Detailed clinical characteristics were collected on these patients. We designed a new method to estimate human leukocyte antigen (HLA)-corrected tumor mutation burden (TMB), a modification which considers the loss of heterozygosity of HLA from conventional TMB. We carried out external validation of our findings utilizing 89 NSCLC samples and 110 melanoma samples from two independent cohorts of immunotherapy-treated patients.
Homology-dependent recombination deficiency was identified in 37 patients (18.7%) and was associated with longer progression-free survival (PFS; P = 0.049). Using the HLA-corrected TMB, non-responders to ICIs were identified, despite having a high TMB (top 25%). Ten patients (21.3% of the high TMB group) were reclassified from the high TMB group into the low TMB group. The objective response rate (ORR), PFS, and overall survival (OS) were all lower in these patients compared with those of the high TMB group (ORR: 20% versus 59%, P = 0.0363; PFS: hazard ratio = 2.91, P = 0.007; OS: hazard ratio = 3.43, P = 0.004). Multivariate analyses showed that high HLA-corrected TMB was associated with a significant survival advantage (hazard ratio = 0.44, P = 0.015), whereas high conventional TMB was not associated with a survival advantage (hazard ratio = 0.63, P = 0.118). Applying this approach to the independent cohorts of 89 NSCLC patients and 110 melanoma patients, TMB-based survival prediction was significantly improved.
HLA-corrected TMB can reconcile the observed disparity in relationships between TMB and ICI responses, and is of predictive and prognostic value for ICI therapies.
•TMB alone is not sufficiently reliable or accurate as a biomarker of response to ICIs in NSCLC.•TMB-based survival prediction is improved by using the HLA-corrected TMB algorithm (TMB in combination with loss of heterozygosity of HLA).•Notably, additional predictive and prognostic value of the HLA-corrected TMB is not limited to certain types of cancer.•The HLA-corrected TMB could be a new strategy for selecting patients who may benefit from immunotherapy.
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