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Background Metastatic RCC with sarcomatoid and/or rhabdoid (S/R) dedifferentiation is an aggressive disease associated with improved response to immune checkpoint therapy (ICT). The outcomes of patients treated with VEGFR-targeted therapies (TT) following ICT progression have not been investigated. Patients and Methods Retrospective review of 57 patients with sarcomatoid (S), rhabdoid (R), or sarcomatoid plus rhabdoid (S + R) dedifferentiation who received any TT after progression on ICT at an academic cancer center. Clinical endpoints of interest included time on TT, overall survival (OS) from initiation of TT, and objective response rate (ORR) by RECIST version 1.1. Multivariable models adjusted for epithelial histology, IMDC risk, prior VEGFR TT, and inclusion of cabozantinib in the post-ICT TT regimen. Results 29/57 patients had S dedifferentiation and 19 had R dedifferentiation. The most frequently used TT was cabozantinib (43.9%) followed by selective VEGFR TT (22.8%). The median time on TT was 6.4 months for all, 6.1 months for those with S dedifferentiation, 15.6 months for R dedifferentiation, and 6.1 months for S + R dedifferentiation. Median OS from initiation of TT was 24.9 months for the entire cohort, and the ORR was 20.0%. Patients with R dedifferentiation had significantly longer time on TT than those with S dedifferentiation (HR 0.44, 95% CI, 0.21-0.94). IMDC risk was associated with OS. Conclusions A subset of patients with S/R dedifferentiation derive clinical benefit from TT after they have progressive disease on ICT. Patients with R dedifferentiation appeared to derive more benefit from TT than those with S dedifferentiation. [ABSTRACT FROM AUTHOR]

Screwworm flies are mass-reared and released along the Panama-Colombia border to prevent reinfestation of Central and North America. The cost of the production facility, labor, and diet materials makes mass-rearing the most expensive component of the program. The mass-rearing diet has a large impact on the quality and quantity of insects produced, both of which are necessary for the successful implementation of the sterile insect technique. The diet currently used to rear screwworm flies in Panama contains dried bovine red blood cells, dried bovine plasma, egg powder, milk replacement powder, cellulose (thickening agent), formaldehyde (antimicrobial), and water. Here, we tested an alternative diet containing 2 chicken by-products, which cost less and are locally available, to replace the egg powder and milk replacement powder currently used in the diet. We used 2 screwworm colony strains in our test, the current production strain (Jamaica) and an early female-lethal strain. The chicken diet performed similarly to the production diet with the Jamaica strain, while further optimization will likely be needed for transgenic strain. Finally, nutritional analysis conducted on 7 diet ingredients will assist with diet optimization and the identification of alternative diet ingredients. [ABSTRACT FROM AUTHOR]

Background Intradermal (ID) vaccination may alleviate COVID-19 vaccine shortages and vaccine hesitancy. Methods Persons aged ≥65 years who were vaccinated with 2-dose ChAdOx1 12–24 weeks earlier were randomized to receive a booster vaccination by either ID (20 µg mRNA-1273 or 10 µg BNT162b2) or intramuscular (IM) (100 µg mRNA-1273 or 30 µg BNT162b2) route. Anti–receptor-binding domain (RBD) immunoglobulin G (IgG), neutralizing antibody (NAb), and interferon gamma (IFN-γ)–producing cells were measured at 2–4 weeks following vaccination. Results Of 210 participants enrolled, 70.5% were female and median age was 77.5 (interquartile range, 71–84) years. Following booster dose, both ID vaccinations induced 37% lower levels of anti-RBD IgG compared with IM vaccination of the same vaccine. NAb titers against ancestral and Omicron BA.1 were highest following IM mRNA-1273 (geometric mean, 1718 and 617), followed by ID mRNA-1273 (1212 and 318), IM BNT162b2 (713 and 230), and ID BNT162b2 (587 and 148), respectively. Spike-specific IFN-γ responses were similar or higher in the ID groups compared with IM groups. ID route tended to have fewer systemic adverse events (AEs), although more local AEs were reported in the ID mRNA-1273 group. Conclusions Fractional ID vaccination induced lower humoral but comparable cellular immunity compared to IM and may be an alternative for older people. Clinical Trials Registration TCTR20220112002. [ABSTRACT FROM AUTHOR]

Flight mills are widely used to investigate insect flight behavior. As technology advances, the means to build a computerized control system for a flight mill has become more accessible in terms of both price and availability of components. However, the specialized electronics and programming knowledge required to build such a system can still present an obstacle to interested parties. Here, we describe a simple and inexpensive flight mill control system that can be easily assembled and operated without specialized experience. The hardware and software components are built around an Arduino single-board microcontroller, which outputs raw data in the form of timestamped detections of rotations of the flight mill arm. This control system is suitable both as the basis for new flight mills and for replacing outdated computer controls on existing flight mills. Additionally, it can be used with any rotary flight mill design that uses an electronic sensor to count rotations. [ABSTRACT FROM AUTHOR]

Background We evaluated the patterns of peripheral Toll-like receptor (TLR) signaling activity and the expression of TLRs and natural killer (NK) cell activation in a cohort of patients experiencing severe hepatitis flares after stopping nucleot(s)ide analogues (NAs) therapy. Methods Samples were collected longitudinally from patients with chronic hepatitis B who were enrolled in a prospective study of NA discontinuation. Patients experiencing hepatitis flares were compared with patients with normal alanine aminotransferase. Peripheral blood mononuclear cells (PBMCs) were stimulated with TLR ligands and cytokine secretion in the cell culture supernatant measured. Expression of TLR2/4, NKG2D, NKp46, and triggering receptor expressed on myeloid cells 1 (TREM-1) on monocytes, NK, and NK-T cells was measured. Results Seventeen patients with severe reactivation hepatitis flares were compared to 12 nonflare patients. Hepatitis flares were associated with increased activity of TLR2–8 and TLR9 signaling in PBMCs at the time of peak flare compared to baseline. Hepatitis flares were also associated with (1) upregulation of TLR2 and (2) TREM-1 receptor expression on NK. There were no differences at baseline between flare patients and nonflare patients. Conclusions Hepatitis flares off NA therapy have a significant innate inflammatory response with upregulation of TLR signaling on peripheral monocytes and TLR2 and TREM-1 expression on NK cells. This implicates the innate immune system in the immunopathogenesis of hepatitis B flares. [ABSTRACT FROM AUTHOR]

Age at maturity is a key life history trait involving a trade-off between survival risk and reproductive investment, and is an important factor for population structures. In ectotherms, a warming environment may have a dramatic influence on development and life history, but this influence may differ between populations. While an increasing number of studies have examined population-dependent reactions with temperature, few have investigated this in the context of maturation timing. Atlantic salmon, a species of high conservation relevance, is a good study species for this topic as it displays considerable variation in age at maturity, of which a large proportion has been associated with a genomic region including the strong candidate gene vgll3. Until now, the effect of this gene in the context of different environments and populations has not been studied. Using a large-scale common-garden experiment, we find strong effects of temperature, population-of-origin, and vgll3 genotype on maturation in 2-year-old male Atlantic salmon (Salmo salar). With a temperature difference of 1.8°C, maturation probability was 4.8 times higher in the warm treatment than the cold treatment. This temperature effect was population-specific and was higher in the southern (60.48°N) compared to the northern (65.01°N) population. The early maturation vgll3 *E allele was associated with a significantly higher maturation probability, but there was no vgll3 interaction with temperature or population. Both body condition and body mass associated with maturation. The body mass association was only present in the warm treatment. Our findings demonstrate that (i) populations can vary in their response to temperature change in terms of age at maturity, (ii) high intrinsic growth could be associated with higher thermal sensitivity for life history variation and (iii) vgll3 effects on age at maturity might be similar between populations and different thermal environments. [ABSTRACT FROM AUTHOR]

Biofilm development in Pseudomonas aeruginosa is regulated by its quorum sensing (QS) systems. It has three major QS systems: LasI/R, RhlI/R and PQS/MvfR. Previous studies showed that phenyllactic acid (PLA) binds to RhlR and PqsR and inhibits the Rhl and PQS QS; and eugenol at sublethal concentration inhibits Las and PQS QS systems. Here, we have demonstrated that a combination of sublethal doses of eugenol and PLA enhanced the inhibition of the QS mediated production of the virulence factors and biofilm development of this pathogen. A combination of 50 μmol l−1 eugenol and 0·3 mmol l−1 PLA significantly inhibited the pyocyanin production, protease activity, swarming motility and cytotoxic activities of P. aeruginosa strain PAO1, whereas eugenol and PLA when added individually to PAO1 cultures were less effective in inhibiting its virulence factor expression. Biofilm formation of PAO1 was reduced by 32, 19 and 87% on glass surfaces; and 54, 49 and 93% on catheter surfaces when treated using 50 μmol l−1 eugenol or 0·3 mmol l−1 PLA and their combinations, respectively. The in vitro finding in the reduction of biofilm development was further validated in vivo using a catheter associated medaka fish biofilm model. Our results indicate that a combination of QS inhibitors targeting different QS pathways should be selected while designing therapeutic molecules to achieve maximum QS mediated biofilm inhibition and clinical outcome against P. aeruginosa. [ABSTRACT FROM AUTHOR]

Background: Multiple instances of flight-associated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission during long-haul flights have been reported during the COVID-19 pandemic. However, comprehensive investigations of passenger risk behaviours, before, during and after the flight, are scarce.Methods: To investigate suspected SARS-CoV-2 transmission during a flight from United Arab Emirates to Australia in July 2020, systematic, repeated polymerase chain reaction (PCR) testing of passengers in hotel quarantine was linked to whole genome sequencing. Epidemiological analyses of in-depth interviews covering behaviours during the flight and activities pre- and post-boarding were used to identify risk factors for infection.Results: Seventeen of the 95 passengers from four different travel origins had PCR-confirmed infection yielding indistinguishable genomic sequences. Two of the 17 passengers were symptomatic within 2 days of the flight, and classified as co-primary cases. Seven secondary cases were seated within two rows of the co-primary cases, but five economy passengers seated further away and three business class passengers were also infected (attack rate = 16% [15/93]). In multivariable analysis, being seated within two rows of a primary case [odds ratio (OR) 7.16; 95% confidence interval (CI) 1.66-30.85] and spending more than an hour in the arrival airport (OR 4.96; 95% CI 1.04-23.60) were independent predictors of secondary infection, suggesting travel-associated SARS-CoV-2 transmission likely occurred both during and after the flight. Self-reported increased hand hygiene, frequent aisle walking and using the bathroom on the plane did not independently affect the risk of SARS-CoV-2 acquisition.Conclusions: This investigation identified substantial in-flight transmission among passengers seated both within and beyond two rows of the primary cases. Infection of passengers in separate cabin classes also suggests transmission occurred outside the cabin environment, likely at the arrival airport. Recognizing that transmission may occur pre- and post-boarding may inform contact tracing advice and improve efforts to prevent future travel-associated outbreaks. [ABSTRACT FROM AUTHOR]

Summary: Background: Eczema (atopic dermatitis; AD) is a very common itchy skin condition affecting 1 in 5 children and up to 1 in 10 adults worldwide. The skin of eczema sufferers is prone to redness, irritation and dryness because it does not form an effective barrier, i.e. the ability of the skin to stop irritants, allergens and microorganisms getting into the body. Skin barrier dysfunction is a hallmark of AD. The regular and liberal (600 g/week for an adult) use of emollients is recommended for all patients with eczema), even between episodes of itching and redness, to soften and soothe the skin. In England alone, almost 9 million prescriptions for emollient creams were issued in 2018, at a cost of over £50 million. Despite this widespread use, relatively little is known about how commonly prescribed emollient creams affect the skin's barrier, and thus the role of moisturizers in AD development and progression remains unclear. We set out to compare three different types of emollient cream and a no‐treatment control. Aim: To compare the barrier‐strengthening properties of a new moisturizer containing urea and glycerol (urea–glycerol cream; UGC), with those of a glycerol‐containing moisturizer (glycerol cream; GC), a simple paraffin cream (PC) with no humectant, and a no‐treatment control (NTC). Methods: This was an observer‐blinded prospective Phase 2 within‐subject multilateral single‐centre randomized controlled trial in adults with AD (Clinical Trials #NCT03901144). The intervention involved 4 weeks of treatment, twice daily, with the three products applied to one of four areas on the forearms the (the fourth area was the untreated control, randomized allocation). Skin properties [dryness, transepidermal water loss (TEWL), hydration and natural moisturizing factor (NMF) levels] were assessed before, during and after treatment to see what happened to the skin's barrier. The primary outcome was skin sensitivity to the irritant sodium lauryl sulfate (SLS) after treatment. We performed tests on the skin before and after treatment to see what happened to the skin's barrier. Results: In total, 49 patients were randomized, completed treatment and included in the analysis. UGC significantly reduced the response to SLS as indicated by a reduction in TEWL compared with NTC (−9.0 g/m2/h; 95% CI −12.56 to −5.49), with PC (−9.0 g/m2/h; 95% CI −12.60 to −5.44) and with GC −4.2 g/m2/h; 95% CI 7.76 to −0.63). Skin moisturization improved at sites treated with UGC compared with NTC and PC, and this was accompanied by concordant changes in dryness and NMF levels. Subgroup analysis suggested FLG‐dependent enhancement of treatment effects. Conclusion: The study showed that not all emollient creams for eczema are equal. The simple paraffin‐based emollient, which represents the most widely prescribed type of emollient cream in England, had no effect on the skin's barrier and reduced the skin's NMF. UGC markedly improved the skin's barrier and protected against irritation. GC performed better than PC, but not as well as UGC. UGC strengthened the skin barrier through a mechanism involving increased NMF levels in the skin, and imparted protection from SLS‐induced irritation. By helping correct a major pathophysiological process, UGC has the potential to improve the long‐term control of AD. The results show that different emollient creams have different effects on our skin, and only certain types have the ability to improve the skin's barrier and protect against irritants that trigger eczema. [ABSTRACT FROM AUTHOR]

Background To determine if dried blood spot specimens (DBS) can reliably detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, we compared the SARS-CoV-2 IgG antibody response in paired serum and eluates from DBS specimens. Methods A total of 95 paired DBS and serum samples were collected from 74 participants (aged 1–63 years) as part of a household cohort study in Melbourne, Australia. SARS-CoV-2 IgG antibodies specific for the receptor-binding domain (RBD) and S1 proteins between serum and eluates from DBS specimens were compared using an FDA-approved ELISA method. Results Among the 74 participants, 42% (31/74) were children and the rest were adults. A total of 16 children and 13 adults were SARS-CoV-2 positive by polymerase chain reaction. The IgG seropositivity rate was similar between serum and DBS specimens (18.9% (18/95) versus 16.8% (16/95)), respectively. Similar RBD and S1-specific IgG levels were detected between serum and DBS specimens. Serum IgG levels strongly correlated with DBS IgG levels (r = 0.99, P  < 0.0001) for both SARS-CoV-2 proteins. Furthermore, antibodies remained stable in DBS specimens for >3 months. Conclusions DBS specimens can be reliably used as an alternative to serum samples for SARS-CoV-2 antibody measurement. The use of DBS specimens would facilitate serosurveillance efforts particularly in hard-to-reach populations and inform public health responses including COVID-19 vaccination strategies. [ABSTRACT FROM AUTHOR]

Summary: Background: The skin of patients with atopic dermatitis is characterized by abnormal stratum corneum lipid levels. Consequently, the lamellar matrices are disrupted and skin barrier function is diminished, increasing skin sensitivity to irritants and allergens. Objectives: To determine whether a cream containing ceramides, triglycerides and cholesterol in a multivesicular emulsion can reinforce the skin barrier and protect against skin irritation. Methods: A randomized observer‐blind intrapatient‐controlled study in 34 adults with dry, eczema‐prone skin was conducted. Each participant underwent 4 weeks of treatment with the test cream on one forearm and lower leg and a reference emollient cream on the other. Skin properties were determined before and after treatment. Lipid structure was assessed by Fourier‐transform infrared spectroscopy using a novel interface. Results: Skin barrier integrity was greater at sites treated with the test cream [effect size for area under the transepidermal water loss curve −162, 95% confidence interval (CI) −206 to −118]. Skin sensitivity to sodium lauryl sulfate was reduced (−0·5 points visual redness, 97·57% CI −1·00 to −0·25), as was transepidermal water loss (−15·3 g m−2 h−1, 95% CI −20·3 to −10·4) compared with the reference. Sites treated with the test cream displayed enhanced lipid chain ordering, which was significantly associated with skin barrier integrity (r = 0·61). Compared with the reference, treatment with the test cream increased hydration (8·61 capacitance units, 95% CI 6·61–10·6) and decreased signs of dryness. Conclusions: The test cream facilitates skin barrier restoration and protects the skin from dryness and irritation. Compared with a commonly prescribed emollient in the UK, the test cream is highly suited to the management of dry, sensitive skin. [ABSTRACT FROM AUTHOR]

In subarctic Newfoundland, age-0 juvenile Atlantic cod (Gadus morhua) settle into coastal habitats in several summer and fall pulses, yielding a broad length-frequency distribution prior to their first winter. The first winter is often associated with physiological and metabolic stress and has been considered a critical survival period determining cohort strength. We evaluated size-structured overwinter mortality and movement using mark–recapture and condition metrics by marking 226 cod in two batches one week apart, in October 2016. We estimated fall and overwinter mortality, and documented movement of fish recaptured in May 2017 using Cormack–Jolly–Seber models. We recaptured 30 marked juveniles. High fall mortality characterized late settling cohorts relative to earlier settling cohorts (16.6%∙d−1 vs. 4.5–7.7% ∙d−1). Overwinter mortality was unexpectedly low (0.0052 and 0.0022% ∙d−1). Individual condition (Fulton's K) of juvenile cod remained high throughout winter across all size groups. We expected higher mortality of juvenile cod and broad dispersal of juveniles over winter (32 weeks). In contrast, our results indicated low mortality and high site-fidelity in their first winter. This study indicates the period leading up to winter is important for survival, suggesting winter is not a survival bottleneck and may even provide a refuge compared to the rest of the year. [ABSTRACT FROM AUTHOR]

Ruxolitinib, a selective inhibitor of Janus kinases 1 and 2, is increasingly being used in allogeneic hematopoietic cell transplantation (HCT) recipients following its approval by the U.S. Food and Drug Administration for the treatment of steroid‐refractory acute graft‐versus‐host disease. Although there is extensive experience using ruxolitinib for patients with myeloproliferative neoplasms, the biologic effects and clinical implications of its dosing, tapering, and discontinuation for allogeneic HCT recipients are incompletely characterized. We describe three allogeneic HCT recipients who developed acute hypoxemic respiratory failure within 3 months of ruxolitinib discontinuation. Radiographic findings included marked bilateral ground‐glass opacities. Systemic corticosteroids and reinitiation of ruxolitinib resulted in rapid clinical improvement in all three patients. All three patients achieved a significant clinical response, with decrease in oxygen requirement and improvement in radiographic changes. Given the increasing use of ruxolitinib in allogeneic HCT recipients, there is significant impetus to characterize the biologic and clinical effects resulting from discontinuation of ruxolitinib, to better tailor treatment plans and prevent potential adverse effects. Considering the increasing use of ruxolitinib in allogeneic hematopoietic cell transplantation recipients, this brief communication emphasizes the ongoing need to better characterize the biologic and clinical effects resulting from the discontinuation of ruxolitinib and to better tailor treatment plans and prevent potential adverse effects. [ABSTRACT FROM AUTHOR]

The current global novel coronavirus disease 2019 (COVID-19) pandemic threatens to derail the uptake of human papillomavirus (HPV) vaccination in low- and lower-middle income countries with major disruptions to routine immunization and the introduction of new vaccines delayed. This has a major impact on the World Health Organization cervical cancer elimination strategy, where it is dependent on HPV vaccination as well as cervical cancer screening and treatment. We discuss current opportunities and barriers to achieve high uptake of HPV vaccination in low- and lower-middle income countries as well as the impact of COVID-19. Implementation of 4 key recommendations for HPV vaccination in low- and lower-middle income countries is needed: increased global financial investment; improved vaccine supply and accelerated use of a single-dose schedule; education and social marketing; and adoption of universal school-based delivery. With the commitment of the global health community, the adoption of these strategies would underpin the effective elimination of cervical cancer. [ABSTRACT FROM AUTHOR]

Background Current commercially available transcatheter aortic valves are stored separately in a glutaraldehyde solution and mounted onto the delivery system by a technical expert during the transcatheter aortic valve implantation (TAVI) procedure. A pre-mounted dry-tissue valve that is crimped on a ready-to-use delivery system could simplify the procedure. The Vienna self-expanding transcatheter valve (P&F, GmbH, Wessling, Germany) is a novel ready-to-use pre-mounted dry-tissue transcatheter aortic valve. There are no prior reports on the efficacy of this valve system. Case summary Here, we report our experience of an implantation of a novel ready-to-use dry-tissue Vienna transcatheter aortic valve in a 72-year-old male with symptomatic severe aortic stenosis and severe left ventricular systolic dysfunction. He had presented with heart failure [N-terminal pro-brain natriuretic peptide (NT-proBNP) level at the admission of 10 600 pg/mL], New York Heart Association Class-3, and recurrent syncope. A 26 mm Vienna valve was successfully implanted via the transfemoral route under conscious sedation. There were no complications. The patient was discharged in a stable condition on the third post-procedure day. At 1-year follow-up, the valve is functioning well with no evidence of structural degeneration (mean gradient 9 mmHg, no valvular regurgitation). Currently, he is asymptomatic with normal left ventricular systolic function on echocardiography (NT-proBNP 57 pg/mL). Discussion To our knowledge, this is the first case of TAVI performed with the dry-tissue pre-mounted VIENNA valve. Our case highlights the feasibility and short-term efficacy of the VIENNA valve. Further safety and durability need to be addressed by a multicentre trial. [ABSTRACT FROM AUTHOR]

Background Age-related chronic conditions are becoming more concerning for people with human immunodeficiency virus (PWH). We aimed to identify characteristics associated with multimorbidity and evaluate for association between multimorbidity and human immunodeficiency virus (HIV) outcomes. Methods Cohorts included PWH aged 45–89 with ≥1 medical visit at one Ryan White HIV/AIDS Program (RWHAP) Southeastern HIV clinic in 2006 (Cohort 1) or 2016 (Cohort 2). Multimorbidity was defined as ≥2 chronic diseases. We used multivariable logistic regression to assess for associations between characteristics and multimorbidity and between multimorbidity and HIV outcomes. Results Multimorbidity increased from Cohort 1 (n = 149) to Cohort 2 (n = 323) (18.8% vs 29.7%, P <.001). Private insurance was associated with less multimorbidity than Medicare (Cohort 1: adjusted odds ratio [aOR] = 0.15, 95% confidence interval [CI] = 0.02–0.63; Cohort 2: aOR = 0.53, 95% CI = 0.27–1.00). In Cohort 2, multimorbidity was associated with female gender (aOR, 2.57; 95% CI, 1.22–5.58). In Cohort 1, black participants were less likely to be engaged in care compared with non-black participants (aOR, 0.72; 95% CI, 0.61–0.87). In Cohort 2, participants with rural residences were more likely to be engaged in care compared with those with urban residences (aOR, 1.23; 95% CI, 1.10–1.38). Multimorbidity was not associated with differences in HIV outcomes. Conclusions Although PWH have access to RWHAP HIV care, PWH with private insurance had lower rates of multimorbidity, which may reflect better access to preventative non-HIV care. In 2016, multimorbidity was higher for women. The RWHAP and RWHAP Part D could invest in addressing these disparities related to insurance and gender. [ABSTRACT FROM AUTHOR]

Background Rotavirus vaccine efficacy is well established. However, it is important to consistently demonstrate the positive impact of vaccination programmes in order to optimize uptake rates and combat vaccine hesitancy. Methods Routine data were used to examine rotavirus vaccine effectiveness in Ireland, including changes in age-specific crude incidence rates (CIRs), hospitalizations and hospital length of stay. National intussusception incidence was interrogated. Vaccination status of vaccine-eligible cases of rotavirus infection was determined. Results Nationally, a reduction in the CIR of rotavirus infection of 77.2% [95% confidence interval (CI) 57.8–88.5%, P <0.001] was observed post-inclusion of the rotavirus vaccine in the primary immunization schedule. A decrease in hospitalizations of 85.5% (95% CI 79.3–90.2%, P <0.001), 86.5% (95% CI 82.9–89.4%, P <0.001) and 78.5% (95% CI 74.7–81.9%, P <0.001) was observed in children aged <1, <2 and <5 years, respectively. Most hospitalizations occurred in infants too young to have been vaccinated. There was no significant difference in median length of stay for children hospitalized with rotavirus infection. Decreased CIRs and hospitalization rates in unvaccinated children aged between 2 and 5 years suggest community immunity. Vaccine non-protection was 0.13%. No increase in the national CIR of intussusception was observed. Conclusions Inclusion of the rotavirus vaccine in the Irish primary immunization schedule has resulted in a significant reduction in the burden of rotavirus infection. However, vaccine hesitancy remains a concern. With new vaccination programmes, risk of vaccine harms should be considered and mitigated in order to protect individuals and the integrity of the programme. [ABSTRACT FROM AUTHOR]

Despite recent taxonomic diversification in studies linking genotype with phenotype, follow-up studies aimed at understanding the molecular processes of such genotype-phenotype associations remain rare. The age at which an individual reaches sexual maturity is an important fitness trait in many wild species. However, the molecular mechanisms regulating maturation timing processes remain obscure. A recent genome-wide association study in Atlantic salmon (Salmo salar) identified large-effect age-at-maturity-associated chromosomal regions including genes vgll3, akap11 and six6, which have roles in adipogenesis, spermatogenesis and the hypothalamic-pituitary-gonadal (HPG) axis, respectively. Here, we determine expression patterns of these genes during salmon development and their potential molecular partners and pathways. Using Nanostring transcription profiling technology, we show development- and tissue-specific mRNA expression patterns for vgll3, akap11 and six6. Correlated expression levels of vgll3 and akap11, which have adjacent chromosomal location, suggests they may have shared regulation. Further, vgll3 correlating with arhgap6 and yap1, and akap11 with lats1 and yap1 suggests that Vgll3 and Akap11 take part in actin cytoskeleton regulation. Tissue-specific expression results indicate that vgll3 and akap11 paralogs have sex-dependent expression patterns in gonads. Moreover, six6 correlating with slc38a6 and rtn1, and Hippo signaling genes suggests that Six6 could have a broader role in the HPG neuroendrocrine and cell fate commitment regulation, respectively. We conclude that Vgll3, Akap11 and Six6 may influence Atlantic salmon maturation timing via affecting adipogenesis and gametogenesis by regulating cell fate commitment and the HPG axis. These results may help to unravel general molecular mechanisms behind maturation. [ABSTRACT FROM AUTHOR]

The article reviews Meredith Monk's opera "ATLAS" performed by the Los Angeles Philharmonic New Music Group at Disney Hall in Los Angeles, California on June 11, 12, and 14, 2019.

Discoveries on involvement of glycan–protein recognition in many (patho)physiological processes are directing attention to exploring the significance of a fundamental structural aspect of sugar receptors beyond glycan specificity, i.e. occurrence of distinct types of modular architecture. In order to trace clues for defining design–functionality relationships in human lectins, a lectin's structural unit has been used as source material for engineering custom-made variants of the wild-type protein. Their availability facilitates comparative analysis toward the stated aim. With adhesion/growth-regulatory human galectin-1 as example, the strategy of evaluating how changes of its design (here, from the homodimer of non-covalently associated domains to (i) linker-connected di- and tetramers and (ii) a galectin-3-like protein) affect activity is illustrated by using three assay systems of increasing degree of glycan complexity. Whereas calorimetry with two cognate disaccharides and array testing with 647 (glyco)compounds disclosed no major changes, galectin histochemical staining profiles of tissue sections that present natural glycome complexity revealed differences between wild-type and linker-connected homo-oligomers as well as between the galectin-3-like variant and wild-type galectin-3 for cell-type positivity, level of intensity at the same site and susceptibility for inhibition by a bivalent glycocompound. These results underscore the strength of the documented approach. Moreover, they give direction to proceed to (i) extending its application to other members of this lectin family, especially galectin-3 and (ii) then analyzing impact of architectural alterations on cell surface lattice formation and ensuing biosignaling systematically, considering the variants' potential for translational medicine. [ABSTRACT FROM AUTHOR]

Inflammatory fibroid polyps (IFP) are rare benign lesions arising from the submucosa of the gastrointestinal tract, most commonly found in the stomach and small intestine. IFPs are very rarely found in the rectum, with only a few reported cases, and their presentation is quite varied. The patient is a 53 year old male who underwent routine screening colonoscopy, during which a lobular mass of the proximal rectum was discovered. The patient subsequently underwent an endoscopic ultrasound (EUS) with fine needle aspiration (FNA) biopsy. Pathology displayed scant spindle cells with benign glandular epithelium suspicious for a spindle cell neoplasm. The mass was excised transanally. The morphological and immunohistochemical findings supported the diagnosis of inflammatory fibroid polyp. Although this is not a malignant tumor, the treatment and surveillance guidelines have not been determined and there is no standard of care. [ABSTRACT FROM AUTHOR]

Members of the Culex pipiens complex differ in physiological traits that facilitate their survival in diverse environments. Assortative mating within the complex occurs in some regions where autogenous (the ability to lay a batch of eggs without a blood meal) and anautogenous populations are sympatric, and differences in mating behaviors may be involved. For example, anautogenous populations mate in flight/swarms, while autogenous populations often mate at rest. Here, we characterized flight activity of males and found that anautogenous strain males were crepuscular, while autogenous strain males were crepuscular and nocturnal, with earlier activity onset times. We conducted quantitative trait locus (QTL) mapping to explore the genetic basis of circadian chronotype (crepuscular vs. crepuscular and nocturnal) and time of activity onset. One major-effect QTL was identified for chronotype, while 3 QTLs were identified for activity onset. The highest logarithm of the odds (LOD) score for the chronotype QTL coincides with a chromosome 3 marker that contains a 15-nucleotide indel within the coding region of the canonical clock gene, cryptochrome 2. Sequencing of this locus in 7 different strains showed that the C-terminus of CRY2 in the autogenous forms contain deletions not found in the anautogenous forms. Consequently, we monitored activity in constant darkness and found males from the anautogenous strain exhibited free running periods of ~24 h while those from the autogenous strain were ~22 h. This study provides novel insights into the genetic basis of flight behaviors that likely reflect adaptation to their distinct ecological niches. [ABSTRACT FROM AUTHOR]

Background To date, no study has examined influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza-associated hospitalizations during pregnancy. Methods The Pregnancy Influenza Vaccine Effectiveness Network (PREVENT) consisted of public health or healthcare systems with integrated laboratory, medical, and vaccination records in Australia, Canada (Alberta and Ontario), Israel, and the United States (California, Oregon, and Washington). Sites identified pregnant women aged 18 through 50 years whose pregnancies overlapped with local influenza seasons from 2010 through 2016. Administrative data were used to identify hospitalizations with acute respiratory or febrile illness (ARFI) and clinician-ordered real-time reverse transcription polymerase chain reaction (rRT-PCR) testing for influenza viruses. Overall IVE was estimated using the test-negative design and adjusting for site, season, season timing, and high-risk medical conditions. Results Among 19450 hospitalizations with an ARFI discharge diagnosis (across 25 site-specific study seasons), only 1030 (6%) of the pregnant women were tested for influenza viruses by rRT-PCR. Approximately half of these women had pneumonia or influenza discharge diagnoses (54%). Influenza A or B virus infections were detected in 598/1030 (58%) of the ARFI hospitalizations with influenza testing. Across sites and seasons, 13% of rRT-PCR-confirmed influenza-positive pregnant women were vaccinated compared with 22% of influenza-negative pregnant women; the adjusted overall IVE was 40% (95% confidence interval = 12%–59%) against influenza-associated hospitalization during pregnancy. Conclusion Between 2010 and 2016, influenza vaccines offered moderate protection against laboratory-confirmed influenza-associated hospitalizations during pregnancy, which may further inform the benefits of maternal influenza vaccination programs. [ABSTRACT FROM AUTHOR]

We study the revenue management (RM) problem encountered in airport car parks, with the primary objective to maximize revenues under a continuous-time framework. The implementation of pre-booking systems for airport car parks has spread rapidly around the world and pre-booking is now available in most major airports. Currently, most RM practises in car parks are simple adjustments of those developed for hotels, exploiting the similarities between the two industries. However, airport car parks have a distinct setting where the price per day of a parking space is heavily discounted by the length of stay (LoS) of the booking. This is because the customer decision tends to be made after the length of the trip is already set, and it becomes a choice between parking or alternative modes of transport. Consequently, the LoS becomes a critical variable for revenue optimization. Since customers are able to book the parking by the minute, the resulting state space is very large, making a conventional network solution intractable. Instead, decomposed single-resource problems need to be considered. Here we develop a bid-price control strategy to manage the bookings and propose novel approaches to define such bid prices depending on the LoS, which could be utilized in real-time RM algorithms. Managing stochastic car park bookings by LoS in the decomposed single-resource approximation allowed us to achieve within 5% of the expected revenues for a multi-resource approximation, with a fraction of the computational effort. When expected demand exceeds the available parking capacity, the method increases the revenues by up to 45% relative to the first come, first served acceptance policy. [ABSTRACT FROM AUTHOR]

Intimal stiffening has been linked with increased vascular permeability and leukocyte transmigration, hallmarks of atherosclerosis. However, recent evidence indicates age-related intimal stiffening is not uniform but rather characterized by increased point-to-point heterogeneity in subendothelial matrix stiffness, the impact of which is much less understood. To investigate the impact of spatially heterogeneous matrix rigidity on endothelial monolayer integrity, we develop a micropillar model to introduce closely-spaced, step-changes in substrate rigidity and compare endothelial monolayer phenotype to rigidity-matched, uniformly stiff and compliant substrates. We found equivalent disruption of adherens junctions within monolayers on step-rigidity and uniformly stiff substrates relative to uniformly compliant substrates. Similarly, monolayers cultured on step-rigidity substrates exhibited equivalent percentages of leukocyte transmigration to monolayers on rigidity-matched, uniformly stiff substrates. Adherens junction tension and focal adhesion density, but not size, increased within monolayers on step-rigidity and uniformly stiff substrates compared to more compliant substrates suggesting that elevated tension is disrupting adherens junction integrity. Leukocyte transmigration frequency and time, focal adhesion size, and focal adhesion density did not differ between stiff and compliant sub-regions of step-rigidity substrates. Overall, our results suggest that endothelial monolayers exposed to mechanically heterogeneous substrates adopt the phenotype associated with the stiffer matrix, indicating that spatial heterogeneities in intimal stiffness observed with age could disrupt endothelial barrier integrity and contribute to atherogenesis. [ABSTRACT FROM AUTHOR]

Aim: The effect of anacardic acid impregnation on catheter surfaces for the prevention of Staphylococcus aureus attachments and biofilm formations were evaluated. Methods and Results: Silicon catheter tubes were impregnated using different concentrations of anacardic acids (0·002–0·25%). Anacardic acids are antibacterial phenolic lipids from cashew nut (Anacardium occidentale) shell oil. Anacardic acid‐impregnated silicon catheters revealed no significant haemolytic activity and were cytocompatible against fibroblast cell line (L929). Sustained release of anacardic acids was observed for 4 days. Anacardic acid‐impregnated silicon catheters efficiently inhibited S. aureus colonization and the biofilm formation on its surface. The in vivo antibiofilm activity of anacardic acid‐impregnated catheters was tested in an intraperitoneal catheter‐associated medaka fish infection model. Significant reduction in S. aureus colonization on anacardic acid‐impregnated catheter tubes was observed. Conclusions: Our data suggest that anacardic acid‐impregnated silicon catheters may help in preventing catheter‐related staphylococcal infections. Significance and Impact of the Study: This study opens new directions for designing antimicrobial phytochemical‐coated surfaces with ideal antibiofilm properties and could be of great interest for biomedical research scientists. [ABSTRACT FROM AUTHOR]

Species complexes are common in the Neotropical flora, and the Pagamea guianensis complex is one of the most widespread groups of species in the Amazonian white-sand flora. Previous analyses suggested the occurrence of ten species in this group, but species limits remained unclear due to poor sampling, morphological overlap and low molecular variation. Here we present the most comprehensive population and molecular sampling across the geographical distribution of the P. guianensis complex to date in order to test the monophyly of this group and to clarify species limits. Using a high-throughput DNA sequencing approach, we sequenced 431 loci (>34 M bases) for 179 individuals. We applied phylogenetic and species tree analyses to resolve phylogenetic relationships among the sampled individuals. Species delimitation was inferred based on genomic data, and we tested whether hypothesized species could be differentiated using morphological, ecological and near-infrared spectroscopy data. We confirm the monophyly of the P. guianensis complex and accept 15 distinct and well-supported lineages, here proposed as 14 species and one subspecies. Our findings highlight the importance of multiple lines of evidence from independent datasets in the process of species delimitation and species discovery in species complexes in the Neotropics. [ABSTRACT FROM AUTHOR]

Financial incentives offered by state property tax programs are a means of promoting goods and services from private forestland. Identified by a 50-state review in 2014-2015, these incentives often require adherence to several conditions including valid ownership and use of forestland, correct size of parcel and suitable forest conditions, implementation of professionally prepared forest management plan, notifying authorities of intent to harvest timber, willingness to participate in reviews and inspections, and an understanding of potential financial or procedural penalties. Implementation of these administrative conditions may require the involvement of several agencies at many levels of government, most frequently being offices of local governments plus supporting roles of citizen advisory committees and boards, tax review appeals and equalization boards, forestry boards and commissions, forestry divisions within state natural resource departments, and state departments of finance and revenue. [ABSTRACT FROM AUTHOR]

Background. Children with acute respiratory tract infection (ARTI) frequently exhibit virus-virus codetection, yet the clinical significance of ARTI remains contentious. Using data from a prospective cohort of children with influenza-like illness, we examined the virology of ARTI and determined the clinical impact of virus-virus codetection. Methods. Children aged 6 to 59 months who presented to a tertiary pediatric hospital between influenza seasons 2008 and 2012 with fever and acute respiratory symptoms were enrolled, and nasal samples were collected. Respiratory viruses were identified by culture and polymerase chain reaction. We compared demographics, presenting symptoms, and clinical outcomes of children with a single-virus infection and those in whom 2 or more viruses were detected (virus-virus codetection). We used logistic regression models and estimated marginal means to calculate the adjusted odds ratios and probabilities of symptom presentation, prescription of antibiotics, and hospitalization. Results. Of 2356 children, a virus was detected in 1630 (69.2%) of them; rhinovirus (40.8%), influenza (29.5%), and respiratory syncytial virus (26.4%) were detected most commonly. Two or more viruses were detected in 25% of these children. After we adjusted for demographic factors, children with virus-virus codetection had greater odds of presenting with cough (adjusted odds ratio [aOR], 1.9; 95% confidence interval [CI], 1.2-3.1) and rhinorrhea (aOR, 1.8; 95% CI, 1.1-2.9) than those with a single-virus infection, although both symptoms were common. Children with influenza and respiratory syncytial virus combined had the highest probability of hospitalization (55%; 95% CI, 35%-73%), which was significantly greater than for those with influenza infection alone (22%; 95% CI, 16%-29%). Conclusions. Overall, virus-virus codetection has limited impact on clinical severity among children with influenza-like illness. However, infection with specific pathogen pairs might be associated with more severe outcomes. Routine diagnostics to identify specific viruses should be restricted to common pathogens. [ABSTRACT FROM AUTHOR]

Background. The duration of antibody response following reduced human papillomavirus (HPV) vaccine doses has not been determined. We compared the antibody responses in girls previously vaccinated with zero, 1, 2, or 3 doses of quadrivalent HPV vaccine (4vHPV; Gardasil, Merck) 6 years previously. Methods. A prospective cohort study was undertaken in 200 Fijian girls 15-19 years of age. Approximately equal numbers of girls from 2 main ethnic groups (Fijians of Indian descent [FID] and Indigenous Fijians [iTaukei]) in Fiji were recruited for each dosage groups. Blood was drawn before and 28 days following a single dose of bivalent HPV vaccine (2vHPV; Cervarix, GlaxoSmithKline). We measured neutralizing antibodies (NAb) against HPV-6, -11, -16, and -18 using the pseudovirion-based neutralization assay. Results. After 6 years (before a dose of 2vHPV was given), the geometric mean NAb titers for all 4 HPV types were not statistically different between 2-dose (2D) and 3-dose (3D) recipients: HPV-6 (3D: 2216 [95% confidence interval {CI},1695-2896]; 2D: 1476 [95% CI, 1019-2137]; P = .07), HPV-11 (3D: 4431 [95% CI, 3396-5783]; 2D: 2951 [95% CI, 1984-4390]; P = .09), HPV-16 (3D: 3373 [95% CI, 2511-4530]; 2D: 3275 [95% CI, 2452-4373]; P = .89); HPV-18 (3D: 628 [95% CI: 445-888]; 2D: 606 [95% CI, 462-862]; P = .89), and were higher in FID than iTaukei girls. Although 1-dose recipients had significantly lower NAb titers than 2-/3-dose recipients, their NAb titers were 5- to 30-fold higher than unvaccinated girls. Post-2vHPV NAb titers against HPV-16 and -18 were not statistically different between girls who received 1, 2, or 3 doses of 4vHPV previously. Conclusions. Two doses of 4vHPV provide similar NAb titers as 3 doses for 6 years, although the clinical significance is unknown. A single dose of 4vHPV elicits antibodies that persisted for at least 6 years, and induced immune memory, suggesting possible protection against HPV vaccine types after a single dose of 4vHPV. [ABSTRACT FROM AUTHOR]

Many fish species that are separated into genetically distinct populations are exploited as mixed stocks and this creates challenges for a sustainable management. European whitefish in the Baltic Sea represents one of these species forming sea- and river-spawning ecotypes, which are further divided into local populations. This study evaluated the effect of combining genetic markers with an adaptive meristic trait (gillraker count, GRC) on the performance of mixed-stock analysis (MSA) of Baltic whitefish. Using 586 individuals from 13 spawning locations, a simulated mixtures analysis showed that the combination of GRC and nine microsatellites improves both the accuracy and precision of MSA for distinguishing two sympatric ecotypes. When applied to gill-net fishery samples (758 fish) collected around the Å land Islands, the estimated stock composition showed a large temporal shift in abundance of two ecotypes between June and November, with decreasing frequency of river spawners in autumn. Our results indicate that combining neutral genetic markers with the adaptive meristic trait provides a useful fisheries monitoring tool for conservation and management of two sympatric whitefish ecotypes in the Baltic Sea. [ABSTRACT FROM AUTHOR]

The article reviews the opera performance Donnerstag aus Licht (Thursday from Light) by composer Karlheinz Stockhausen which had created controversies with the performances.

Background: Patients with hip fracture have complex medical issues, both at the time of admission and after discharge from hospital. We have observed a surge in patient-initiated and carer-initiated contacts with general physicians (GPs) for periods longer than those usually reported, in a series of patients sustaining fractures from July 2008 to September 2013.Objectives: To establish (1) the frequency of contact with GPs (primary outcome) and (2) the factors influencing the frequency of different modes of contact.Methods: Ten GP practices in West Northumberland were asked to retrospectively identify patients sustaining hip fractures, and to provide data on the number of GP contacts (patient visits to GP, telephone consultations, GP visits to patient's home) up to 1 year before and 1 year after fracture. Generalised linear models (GLM) were constructed using number of postfracture GP contacts as response variable; age, gender, residential status, number of prefracture contacts and days to contact postfracture were covariates.Results: Each patient recorded cumulative 8.4 GP contacts before and 10.79 contacts after fracture. There were significantly more telephone contacts with GPs and GP home visits, but significantly fewer patient visits to GP clinics. In the GLM analysis, patient age and number of prefracture GP contacts predicted all types of postfracture contacts, while gender was not. Patients discharged home visited their GPs five times more frequently than those discharged to institutional care.Conclusions: After hip fractures, telephone contacts and GP visits to patients' homes increase, but patient visits to GP clinics decrease, influenced by age and residential status. [ABSTRACT FROM AUTHOR]

Background: Mechanisms by which spontaneous clearance of acute hepatitis C occurs are unclear. A critical role for the innate immune system and IFNL4 polymorphisms has been proposed. This study investigates whether Toll-like receptor (TLR) expression and signaling during acute hepatitis C correlates with clinical outcomes.Methods: Participants identified from the Australian Trial in Acute Hepatitis C and the Networks study were followed longitudinally from the time of diagnosis of acute hepatitis C. Peripheral blood mononuclear cells (PBMCs) and plasma were collected at and 2 time points after diagnosis. At each time point, TLR2, TLR4, and CD86 expression on peripheral blood monocytes, natural killer (NK) cells, and NK T cells was measured, as well as the response of PBMCs to stimulation with TLR ligands. Cytokine and chemokine levels were measured in stimulated PBMCs and plasma.Results: We identified 20 participants with acute hepatitis C (10 with hepatitis C virus [HCV] monoinfection and 10 with HCV and human immunodeficiency virus coinfection). Eleven participants (55%) spontaneously cleared HCV. Acute hepatitis C and spontaneous clearance was associated with lower TLR4 expression on monocytes (P = .009) and NK cells (P = .029). Acute hepatitis C and spontaneous clearance was also associated with a reduced interferon γ response to TLR4 (P = .038) and TLR7/8 stimulation (P = .035), a reduced interleukin 6 response to TLR7/8 stimulation (P = .037), and reduced IFN-γ-inducible protein 10 (IP-10) response to TLR2 stimulation (P = .042). Lower plasma IP-10 levels were associated with spontaneous clearance (P = .001).Conclusions: These findings implicate TLR4 signaling as playing a critical role in the outcome of acute hepatitis C. [ABSTRACT FROM AUTHOR]

Small trees and shrubs play an important role in forest diversity and regeneration and may contribute substantially to ecosystem fluxes of carbon and water; however, relatively little attention is given to quantifying the contribution of small trees to forest processes. One reason for this may be that the allometric equations developed for large trees tend to systematically underestimate structural variables such as biomass and foliage area when applied to small trees, both on an individual tree level and at the stand level. To test this hypothesis, we developed allometric equations for trees < 10 cm dbh (D) for seven dependent variables (woody, foliage, and total biomass; woody, foliage, and whole-plant surface area; and sapwood area) and compared these new equations with the existing equations for large trees. We found significant differences between small tree and large tree equations for most variables and showed that equations for large trees tend to underestimate the structural characteristics of small trees. When we applied new size-specific equations to forest survey data representing a chronosequence of forest development, estimates of small tree biomass increased 30-73% and estimates of foliage area increased 72-142% compared with results using only equations for large trees. These results suggest that small trees can contribute substantially to forest structure and associated ecosystem fluxes, especially in stands with a large proportion of small trees. However, size-specific equations for small trees did not substantially change the estimates of forest biomass in these stands, and the need to develop size-specific equations may depend on the variables of interest. [ABSTRACT FROM AUTHOR]

The luminous bacterial symbionts of anomalopid flashlight fish are thought to be obligately dependent on their hosts for growth and share several aspects of genome evolution with unrelated obligate symbionts, including genome reduction. However, in contrast to most obligate bacteria, anomalopid symbionts have an active environmental phase thatmay be important for symbiont transmission. Here we investigated patterns of evolution between anomalopid symbionts compared with patterns in free-living relatives and unrelated obligate symbionts to determine if trends common to obligate symbionts are also found in anomalopid symbionts. Two symbionts, “Candidatus Photodesmus katoptron” and “Candidatus Photodesmus blepharus,” have genomes that are highly similar in gene content and order, suggesting genome stasis similar to ancient obligate symbionts present in insect lineages. This genome stasis exists in spite of the symbiont’s inferred ability to recombine, which is frequently lacking in obligate symbionts with stable genomes.Additionally,weusedgenome comparisonsandtestsof selection toinferwhichgenesmaybeparticularly important for the symbiont’s ecology compared with relatives. In keeping with obligate dependence, substitution patterns suggest that most symbiont genes are experiencing relaxed purifying selection compared with relatives. However, genes involved in motility and carbon storage, which are likely to be used outside the host, appear to be under increased purifying selection. Twochemoreceptor chemotaxis genes are retained by both species and show high conservation with amino acid sensing genes, suggesting that the bacteria may actively seek out hosts using chemotaxis toward amino acids, which the symbionts are not able to synthesize. [ABSTRACT FROM AUTHOR]

Background. Although antenatal influenza vaccination is an important public health intervention for preventing serious infection in pregnant women and newborns, reported vaccine coverage is often <50%. Concern for the safety to the fetus is a commonly cited reason for vaccine hesitancy and refusal. The incidence of stillbirth following pandemic vaccination has been previously studied; however, no population-based study has evaluated the incidence of stillbirth following seasonal trivalent influenza vaccination. Methods. We used probabilistic linking of perinatal and maternal vaccination records to establish a cohort of 58 008 births occurring between April 2012 and December 2013. Stillbirth was defined as birth ≥20 weeks' gestation with an Apgar score of zero at 1 and 5 minutes following delivery. Cox regression models adjusted for maternal smoking, Indigenous status, and propensity for vaccination were used to calculate adjusted hazard ratios (aHRs) in vaccinated and unvaccinated mothers. Results. A total of 5076 (8.8%) pregnant women received trivalent influenza vaccine and 377 stillbirths occurred. There were 5.0 and 3.0 stillbirths per 100 000 pregnancy-days among unvaccinated and vaccinated women, respectively. After adjustment, stillbirth was 51% less likely among vaccinated vs unvaccinated mothers (aHR, 0.49; 95% confidence interval [CI], .29–.84). The largest relative reduction in stillbirths was observed for births occurring just after influenza season (aHR, 0.33; 95% CI, .12–.88). Conclusions. Mothers who received seasonal TIV during pregnancy were significantly less likely to experience stillbirth compared with unvaccinated mothers. These results support the safety of seasonal influenza immunization during pregnancy and suggest a protective effect. [ABSTRACT FROM AUTHOR]

The article discusses the musical career of composer Karlheinz Stockhausen, focusing on a series of seventeen volumes titled "Texte zur Musik" that contain essays, sketches and interviews in respect of Stockhausen's thinking. Topics discussed include compositions written by Stockhausen, and his summer courses in his hometown of Kurten in Germany.

Objective: To report the long-term follow-up of subsolid nodules (SSNs) detected in participants of a prospective low-dose CT lung cancer screening cohort, and to investigate the utility of the PanCan model in stratifying risk in baseline SSNs. Methods: Participants underwent a baseline scan, two annual incidence scans and further follow-up scans for the detected nodules. All SSNs underwent a minimum of 2 years of follow-up (unless resolved or resected). Risk of malignancy was estimated using the PanCan model: discrimination [area under the receiver-operating characteristic curve (AUC)] and calibration (Hosmer-Lemeshow goodness-of-fit test) were assessed. The Mann-Whitney (U-Wilcoxon test was used to compare estimated risk between groups. Results: 70 SSNs were detected in 41 (16.0%) out of 256 total participants. Median follow-up period was 25.5 months (range 2.0-74.0 months). 29 (41.4%) SSNs were transient. Five (7.1%) SSNs were resected, all found to be Stage I lung adenocarcinoma, including one SSN stable in size for 3.0 years before growth was detected. The PanCan model had good discrimination for the 52 baseline SSNs (AUC = 0.89; 95% confidence interval 0.76-1); the Hosmer-Lemeshow goodness-of-fit test was non-significant (p = 0.27), Estimated risk was significantly higher in the baseline SSNs found to be cancer vs those not found to be cancer after 2-6 years of follow-up (p < 0.01). Conclusion: Our findings support a long-term follow-up approach for screen-detected SSNs for 3 years or longer. The PanCan model appeared discriminatory and well calibrated in this cohort. Advances in knowledge: The PanCan model may have utility in identifying low-risk SSNs which could be followed with less frequent CT scans. [ABSTRACT FROM AUTHOR]

Objective: Pituitary adenomas (PA) are among the most common human neoplasms. To describe the epidemiology and assess the disease burden of clinically significant PAs, population-based studies are needed. Iceland has a small well-defined population. The aim of this study is to describe the epidemiology of PAs in Iceland over an expanded period of time. Design: This is a retrospective observational study, including all PAs diagnosed in Iceland from 1955 to 2012. Methods: Extensive clinical information was gathered in a database. Prevalence rates for all PA subtypes were calculated along with standardized incidence rates (SIR). Sex ratios and relationships with adenoma size, age, and symptoms were assessed. Results: We identified 471 individuals: 190 men and 281 women. Total prevalence in 2012 was 115.57/100 000, prolactinomas were most prevalent (54.37/100 000) followed by non-functioning adenomas (NFPAs) (42.32/100 000). Throughout the period, NFPAs were most common (43.0%) followed by prolactinomas (39.9%) and 11.3% had acromegaly and 5.7% Cushing's disease. Women are diagnosed younger with smaller adenomas. Total SIR has increased significantly and is now 5.8/100 000 per year. Conclusion: In this nationwide study spanning six decades, we have confirmed PAs rising prevalence and incidence rates noted in recent studies. We demonstrated higher overall prevalence and incidence rates than ever previously recorded with an increasing predominance of NFPAs, which is not explained by incidental findings alone. There is a relationship with the introduction of imaging modalities, but the vast majority of patients are symptomatic at diagnosis. This underlines the importance of increased awareness, education, and appropriate allocation of resources for this growing group of patients. [ABSTRACT FROM AUTHOR]

We evaluated the influence of environmental exposure of juvenile Atlantic cod (Gadus morhua) to inform interpretations of natal origins and movement patterns using otolith geochemistry. Laboratory rearing experiments were conducted with a variety of temperature (~5, 8.5, and 12°C) and salinity (~25, 28.5, and 32 PSU) combinations. We measured magnesium (Mg), manganese (Mn), strontium (Sr), and barium (Ba), expressed as a ratio to calcium (Ca), using laser ablation inductively coupled plasma mass spectrometry (ICP-MS), and stable carbon (δ13C) and oxygen (δ18O) isotopes using isotope ratio monitoring mass spectrometry. Temperature and salinity significantly affected all elements and isotopes measured, except salinity on Mg:Ca. We detected significant interactions among temperature and salinity for Mn:Ca and Ba:Ca partition coefficients (ratio of otolith chemistry to water chemistry), with significant temperature effects only detected in the 32 and 28.5 PSU salinity treatments. Similarly, we detected a significant interaction between temperature and salinity in incorporation of δ13C, with a significant temperature effect except at intermediate salinity. These results support the contention that environmental mediation of otolith composition varies among species, thus limiting the ability of generalized models to infer life history patterns from chemistry. Our results provide essential baseline information detailing environmental influence on juvenile Atlantic cod otolith composition, punctuating the importance of laboratory validations to translate species-specific otolith composition when inferring in situ life histories and movements. [ABSTRACT FROM AUTHOR]

Sulfur hexafluoride (SF6) is widely used as a tracer gas because of its detectability at low concentrations. This attribute of SF6 allows the quantification of both small-scale flows, such as leakage, and large-scale flows, such as atmospheric currents. SF6's high detection sensitivity also facilitates greater usage efficiency and lower operating cost for tracer deployments by reducing quantity requirements. The detectability of SF6 is produced by its high molecular electronegativity. This property provides a high potential for negative ion formation through electron capture thus naturally translating to selective detection using negative ion chemical ionization mass spectrometry (NCI-MS). This paper investigates the potential of using gas chromatography (GC) with NCI-MS for the detection of SF6. The experimental parameters for an ultra-trace SF6 detection method utilizing minimal customizations of the analytical instrument are detailed. A method for the detection of parts per trillion (ppt) level concentrations of SF6 for the purpose of underground ventilation tracer gas analysis was successfully developed in this study. The method utilized a Shimadzu gas chromatography with negative ion chemical ionization mass spectrometry system equipped with an Agilent J&W HP-porous layer open tubular column coated with an alumina oxide (Al2O3) S column. The method detection limit (MDL) analysis as defined by the Environmental Protection Agency of the tracer data showed the method MDL to be 5.2 ppt. [ABSTRACT FROM AUTHOR]

Over the last 60 years, multiple studies have attributed sugar maple (Acer saccharum Marsh.) dieback and decline to nutrient status, interaction and tree stress. Site differences in deficient, toxic or antagonistic levels of soil calcium, magnesium, phosphorus, potassium, manganese and aluminium are correlated with mortality and dieback in many studies. In general, a single nutrient is rarely determined to be responsible for poor sugar maple health. Other factors such as defoliation, management, climate fluctuations and soil biota can play key roles in dieback. Nutrient stresses can greatly increase the risk of injury and mortality from other biotic or abiotic stresses. Anthropogenic inputs and climate change may also cause perturbation of nutrient or pH thresholds for sugar maple. Therefore, historical sugar maple sites may no longer be suitable to support a healthy sugar maple forest under current management regimes. The following is a review of locations, symptoms and studies of the relationship of mineral stress to sugar maple health, which will be useful information for forest resource managers to consider when faced with maple health issues. Conclusions developed from this review are as follows: (1) land managers should consider soil nutrition in decision-making concerning sugar maple, (2) standardization of evaluation methods for tree nutrition is somewhat lacking and (3) additional multidisciplinary research is needed to clarify the interacting factors affecting sugar maple health and nutrition. [ABSTRACT FROM AUTHOR]

Andean uplift and the collision of North and South America are thought to have major implications for the diversification of the Neotropical biota. However, few studies have investigated how these geological events may have influenced diversification. We present a multilocus phylogeny of 102 Protieae taxa (73% of published species), sampled pantropically, to test hypotheses about the relative importance of dispersal, vicariance, habitat specialization, and biotic factors in the diversification of this ecologically dominant tribe of Neotropical trees. Bayesian fossil-calibrated analyses date the Protieae stem at 55 Mya. Biogeographic analyses reconstruct an initial late Oligocene/early Miocene radiation in Amazonia for Neotropical Protieae, with several subsequent late Miocene dispersal events to Central America, the Caribbean, Brazil's Atlantic Forest, and the Chocó. Regional phylogenetic structure results indicate frequent dispersal among regions throughout the Miocene and many instances of more recent regional in situ speciation. Habitat specialization to white sand or flooded soils was common, especially in Amazonia. There was one significant increase in diversification rate coincident with colonization of the Neotropics, followed by a gradual decrease consistent with models of diversity-dependent cladogenesis. Dispersal, biotic interactions, and habitat specialization are thus hypothesized to be the most important processes underlying the diversification of the Protieae. [ABSTRACT FROM AUTHOR]

Hand removal is often recommended as a method for small-scale control of Japanese beetles (Popillia japonica Newman). In this study, we investigated the effectiveness of daily hand removal for controlling damage by Japanese beetles on grape plants. We also investigated whether the timing of the removal (at 0800, 1400, or 1900 hours, or at all 3 periods) influenced the effectiveness of the technique. We found that hand removal significantly lowered the number of beetles on, and consequently the damage to, grape plants relative to nonremoval controls. Of the single removal treatments, removal of beetles at 1900 hours was most effective, with results similar to removing beetles three times per day. The majority of beetles removed from plants during the experiment were female, a pattern that matches our understanding of aggregation formation behavior in the species, and which may serve to enhance the benefits of hand removal. Hand removal seems to work by decreasing the number of feeding beetles, which in turn reduces the release of aggregation kairomones from the plant, and subsequently decreases the attractiveness of the plant to future beetles. [ABSTRACT FROM AUTHOR]

Integrated pest management has proved cost-effective in coping with crop pests. This article identifies characteristics of pests, controls and economic incentives that may make the development of an integrated joint pest management (IJPM) strategy – designed for simultaneous control of multiple pests – worthwhile. We demonstrate via a case study that an IJPM strategy may add considerable value for on-farm corn storage. Critical factors for an IJPM strategy are that the pests are affected by the same environmental variables, but with different thresholds and response functions; controls for one pest impact other pests; and the pests have similar economic importance. [ABSTRACT FROM AUTHOR]

We report here the development of 65 novel microsatellite loci and construction of a composite genetic linkage map for Culex pipiens complex mosquitoes. Microsatellites were identified by in silico screening of the Culex quinquefasciatus genome assembly. Cross-species utility of 73 microsatellites for population studies in C. pipiens sensu stricto and C. quinquefasciatus was evaluated by genotyping a subset of samples collected in Indiana, United States, and Point Fortin, Trinidad. Allele frequencies of 67 microsatellites were within Hardy–Weinberg expectations in both population subsets. A composite linkage map was constructed based on restriction fragment length polymorphism and microsatellite polymorphisms in 12 independent F1 intercross mapping populations. The composite map consists of 61 marker loci totaling 183.9 cM distributed across the 3 linkage groups. These loci cover 29.5, 88.8, and 65.6 cM on chromosomes I–III, respectively, and allow for assignment of 10.4% of the genome assembly and 13.5% of the protein coding genes to chromosome position. Our results suggest that these microsatellites will be useful for mapping and population studies of 2 pervasive species in the C. pipiens complex. Moreover, the composite map presented here will serve as a basis for the construction of high-resolution genetic and physical maps, as well as detection of quantitative trait loci to aid in the investigation of complex genetic traits influencing phenotypes of interest. [ABSTRACT FROM AUTHOR]