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Background Current guidelines advocate a shared decision-making process approach to erectile dysfunction management, and while there is growing interest in regenerative therapies such as stem cell therapy, platelet-rich plasma injections, and low-intensity shockwave therapy for erectile dysfunction, comparative data on the efficacy of these modalities are limited. Aim This systematic review and network meta-analysis aims to compare stem cell therapy, platelet-rich plasma injections, and low-intensity shockwave therapy for managing erectile dysfunction and quantify their impact on the International Index of Erectile Function (IIEF). Methods In January 2024, a systematic search of online databases was performed to identify randomized clinical trials related to stem cell therapy, platelet-rich plasma injections, and low-intensity shockwave therapy in erectile dysfunction. Eligible articles reported outcomes using the IIEF score. Data were inputted into Review Manager 5.4 for pairwise meta-analysis. Data were then used to build a network in R Studio. These networks were used to model 200 000 Markov Chains via MonteCarlo sampling. The results are expressed as standardized mean difference (SMD) with 95% credible intervals (CrI). Meta-regression was used to adjust for PDE5is use. Outcomes Impact on the International Index of Erectile Function. Results A total of 16 studies involving 907 patients were analyzed. The standardized mean difference (SMD) vs control for stem cell therapy was 0.92 [95% CrI –0.49, 2.3]. For platelet-rich plasma, the SMD vs control was 0.83 [95% CrI 0.15, 1.5], and for low-intensity shockwave therapy, the SMD vs control was 0.84 [95% CrI 0.49, 1.2]. When stratifying low-intensity shockwave therapy by dose, the SMD vs control at 0.15 mJ/mm2 was 1.1 [95% CrI 0.36, 1.9], while at 0.09 mJ/mm2, it was 0.75 [95% CrI 0.26, 1.2]. Meta-regression adjusting for the administration of PDE5 inhibitors yielded non-significant results. Clinical implications The findings suggest that stem cells, platelet-rich plasma, and low intensity shockwave therapy, particularly at 0.15 and 0.09 mJ/mm2, may offer improvements in erectile function. Strengths and limitations The strength is the robust statistical methods. Limitations are in heterogeneity in control groups and follow-up durations among included studies. Conclusion Shockwave therapy and platelet-rich plasma demonstrated statistically significant improvements, though the clinical relevance and extent of their impact remain questionable. Further research is necessary to determine the efficacy of stem cell therapies for erectile function. [ABSTRACT FROM AUTHOR]

Background Programmed cell death–1 (PD-1) and programmed cell death–ligand 1 (PD-L1) inhibitors have poor efficacy in patients with trastuzumab-resistant advanced HER2-positive breast cancer. Tucatinib is a potent, selective anti-HER2 tyrosine kinase inhibitor with proven clinical benefit in the advanced setting in patients with trastuzumab resistance. We investigated if tucatinib can alter the tumor microenvironment and if this could be harnessed for therapeutic efficacy. Methods We investigated the antitumor efficacy and contribution of the immune response of tucatinib using 2 immunocompetent, HER2-positive murine breast cancer models (trastuzumab-sensitive H2N113; trastuzumab-resistant Fo5) and the efficacy of tucatinib with trastuzumab and PD-1 or PD-L1 checkpoint inhibitors. Results In both models, tucatinib statistically significantly inhibited tumor growth and demonstrated dose-dependent efficacy. Ex vivo analysis by flow cytometry of tumor-infiltrating lymphocytes in mice treated with tucatinib showed increased frequency, higher proliferation, and enhanced effector function of CD8+ effector memory T cells. Tucatinib treatment also increased frequency of CD8+PD-1+ and CD8+TIM3+ T cells, CD49+ natural killer cells, monocytes, and major histocompatibility complex II expression on dendritic cells and macrophages and a decrease in myeloid-derived suppressor cells. Gene expression analysis revealed statistically significant enrichment in pathways associated with immune activation, type I and II interferon response, adaptive immune response, and antigen receptor signaling. In vivo, tucatinib and α-PD-L1 or α-PD-1 demonstrated statistically significantly increased efficacy and improved survival of mice compared with tucatinib alone. Conclusion Tucatinib modulates the immune microenvironment favorably, and combination treatment with α-PD-L1 or α-PD-1 demonstrated increased efficacy in preclinical HER2-positive tumor models. These findings provide a rationale for investigation of tucatinib and immune checkpoint inhibition in the clinic. [ABSTRACT FROM AUTHOR]

Background Roflumilast is a highly potent phosphodiesterase 4 inhibitor under investigation as a non-steroidal, once-daily cream for atopic dermatitis (AD). Methods INTEGUMENT-PED (NCT04845620) was a Phase 3 parallel-group, double-blind, vehicle-controlled trial. Children aged 2 to 5 years with mild to moderate AD were treated with roflumilast cream 0.05% (n=437) or vehicle (n=215) once-daily for 4 weeks. The primary efficacy endpoint was validated Investigator Global Assessment-Atopic Dermatitis (vIGA-AD) Success (defined as a score of 0 [clear] or 1 [almost clear] with 2-grade improvement from baseline) at Week 4. Secondary endpoints included 75% improvement in Eczema Area and Severity Index (EASI-75). Worst-Itch-Numeric Rating Score (WI-NRS) Success (≥4-point improvement in patients with baseline ≥4), safety, and tolerability were also assessed. Results At Week 4, significantly more roflumilast-treated than vehicle-treated patients achieved vIGA-AD Success (25.4% vs 10.7%; P<0.0001), EASI-75 (39.4% vs 20.6%; P<0.0001), and WI-NRS Success (35.3% vs 18.0%; nominal P=0.0002). Improvement in pruritus was observed by 24 hours after first application (nominal P=0.0014 versus vehicle). Incidence of treatment-emergent adverse events (AEs) was low in both arms, with 98.9% assessed as mild to moderate. AEs occurring in >2% of patients and greater in the roflumilast-treated group were upper respiratory tract infection, diarrhea, and vomiting. For local tolerability, >92% of roflumilast-treated patients reported no or mild sensation across arms at any timepoint. Conclusion In this phase 3 trial, once-daily roflumilast cream 0.05% improved AD in pediatric patients (2 to 5 years of age), while demonstrating favorable safety and tolerability. [ABSTRACT FROM AUTHOR]

Background Roflumilast, a highly potent phosphodiesterase-4 inhibitor, is being investigated as a non-steroidal, once-daily cream for atopic dermatitis (AD). Methods INTEGUMENT-OLE (NCT04804605) was an open-label 52-week safety trial. Patients (N=658) with mild to moderate AD who completed a 4-week randomized vehicle-controlled phase 3 trial of roflumilast cream continued or switched to once-daily roflumilast cream 0.15% in this open-label extension trial. Starting at Week 4, patients achieving Validated Investigator Global Assessment for AD (vIGA-AD) score of 0 (Clear) switched to twice-weekly (BIW) maintenance dosing. The primary endpoint was safety; secondary endpoints included vIGA-AD, Worst Itch-Numeric Rating Scale (WI-NRS), and Eczema Area and Severity Index (EASI). "Disease control" was defined as duration of vIGA-AD=0/1 on BIW dosing following achievement of vIGA-AD=0. Results With cumulative treatment up to 56 weeks, 36.7% of patients reported treatment-emergent adverse events (AEs); most were mild to moderate in severity. Overall, 4.7% of patients had AEs deemed treatment-related and 3.0% discontinued due to AEs. The most common AEs (>2%) were COVID-19, upper respiratory tract infection, nasopharyngitis, and headache. At Week 52, 55.7%, 61.1%, and 53.6% of patients achieved vIGA-AD=0/1 (Clear/Almost Clear), ≥75% reduction in EASI, and ≥4-point reduction in WI-NRS (among patients aged ≥12 years with baseline WI-NRS ≥4), respectively. Of the 130 (19.8%) patients who achieved disease control, 50% maintained "disease control" for at least 281 days. Conclusion Treatment with roflumilast cream 0.15% demonstrated long-term safety in patients with AD consistent with parent trials and durable efficacy through 52 weeks, including patients who switched to BIW dosing. [ABSTRACT FROM AUTHOR]

Background Neurocysticercosis is a major cause of acquired epilepsy. Larval cysts in the human brain eventually resolve and either disappear or leave a calcification that is associated with seizures. In this study, we assessed the proportion of calcification in parenchymal neurocysticercosis and risk factors associated with calcification. Methods Data for 220 patients with parenchymal NCC from 3 trials of antiparasitic treatment were assessed to determine what proportion of the cysts that resolved 6 months after treatment ended up in a residual calcification at 1 year. Also, we evaluated the risk factors associated with calcification. Results The overall proportion of calcification was 38% (188/497 cysts, from 147 patients). Predictors for calcification at the cyst level were cysts larger than 14 mm (risk ratio [RR], 1.34; 95% confidence interval [CI], 1.02–1.75) and cysts with edema at baseline (RR, 1.39; 95% CI, 1.05–1.85). At the patient level, having had more than 24 months with seizures (RR, 1.25; 95% CI, 1.08–1.46), mild antibody response (RR, 1.14; 95% CI, 1.002–1.27), increased dose albendazole regime (RR, 1.26; 95% CI, 1.14–1.39), lower doses of dexamethasone (RR, 1.36; 95% CI, 1.02–1.81), not receiving early antiparasitic retreatment (RR, 1.45; 95% CI, 1.08–1.93), or complete cure (RR, 1.48; 95% CI, 1.29–1.71) were associated with a increased risk of calcification. Conclusions Approximately 38% of parenchymal cysts calcify after antiparasitic treatment. Some factors associated with calcification are modifiable and may be considered to decrease or avoid calcification, potentially decreasing the risk for seizure relapses. [ABSTRACT FROM AUTHOR]

In many animals, germline development is initiated by proteins and RNAs that are expressed maternally. PIWI proteins and their associated small noncoding PIWI-interacting RNAs (piRNAs), which guide PIWI to target RNAs by base-pairing, are among the maternal components deposited into the germline of the Drosophila early embryo. Piwi has been extensively studied in the adult ovary and testis, where it is required for transposon suppression, germline stem cell self-renewal, and fertility. Consequently, loss of Piwi in the adult ovary using piwi-null alleles or knockdown from early oogenesis results in complete sterility, limiting investigation into possible embryonic functions of maternal Piwi. In this study, we show that the maternal Piwi protein persists in the embryonic germline through gonad coalescence, suggesting that maternal Piwi can regulate germline development beyond early embryogenesis. Using a maternal knockdown strategy, we find that maternal Piwi is required for the fertility and normal gonad morphology of female, but not male, progeny. Following maternal piwi knockdown, transposons were mildly derepressed in the early embryo but were fully repressed in the ovaries of adult progeny. Furthermore, the maternal piRNA pool was diminished, reducing the capacity of the PIWI/piRNA complex to target zygotic genes during embryogenesis. Examination of embryonic germ cell proliferation and ovarian gene expression showed that the germline of female progeny was partially masculinized by maternal piwi knockdown. Our study reveals a novel role for maternal Piwi in the germline development of female progeny and suggests that the PIWI/piRNA pathway is involved in germline sex determination in Drosophila. [ABSTRACT FROM AUTHOR]

The paraventricular nucleus of the hypothalamus (PVH) is a heterogeneous collection of neurons that play important roles in modulating feeding and energy expenditure. Abnormal development or ablation of the PVH results in hyperphagic obesity and defects in energy expenditure whereas selective activation of defined PVH neuronal populations can suppress feeding and may promote energy expenditure. Here, we characterize the contribution of calcitonin receptor–expressing PVH neurons (CalcRPVH) to energy balance control. We used Cre-dependent viral tools delivered stereotaxically to the PVH of CalcR2Acre mice to activate, silence, and trace CalcRPVH neurons and determine their contribution to body weight regulation. Immunohistochemistry of fluorescently-labeled CalcRPVH neurons demonstrates that CalcRPVH neurons are largely distinct from several PVH neuronal populations involved in energy homeostasis; these neurons project to regions of the hindbrain that are implicated in energy balance control, including the nucleus of the solitary tract and the parabrachial nucleus. Acute activation of CalcRPVH neurons suppresses feeding without appreciably augmenting energy expenditure, whereas their silencing leads to obesity that may be due in part due to loss of PVH melanocortin-4 receptor signaling. These data show that CalcRPVH neurons are an essential component of energy balance neurocircuitry and their function is important for body weight maintenance. A thorough understanding of the mechanisms by which CalcRPVH neurons modulate energy balance might identify novel therapeutic targets for the treatment and prevention of obesity. [ABSTRACT FROM AUTHOR]

Tapinarof is a first-in-class, nonsteroidal, topical, aryl hydrocarbon receptor agonist approved by the Food and Drug Administration for the treatment of plaque psoriasis in adults, and under investigation for the treatment of atopic dermatitis (AD) in adults and children. Tapinarof cream 1% once daily (QD) demonstrated significant efficacy vs. vehicle and was well tolerated in adults and adolescents with moderate to severe AD in a previously reported phase 2b trial. The pharmacokinetic (PK) profile of tapinarof across psoriasis and AD trials in adults is characterized by no-to-minimal systemic absorption and decreasing plasma concentrations over the course of treatment. Here, we report PK, tolerability and safety of tapinarof cream 1% QD in adolescents and children down to age 2 years with extensive AD. Adolescents and children with a Validated Investigator Global Assessment scale for Atopic Dermatitis™ (vIGA-AD™) score ≥3 (moderate or worse) and body surface area (BSA) involvement ≥25% (ages 12–17 years) or ≥35% (ages 2–11 years) were enrolled into three age cohorts (2–6, 7–11 and 12–17 years) and were treated with tapinarof cream 1% QD for 4 weeks. Primary endpoints included PK parameters, investigator-assessed Local Tolerability Scale (LTS) scores by visit (overall and for sensitive areas) and treatment-emergent adverse events (TEAEs). Overall, 36 patients (12 per cohort) were enrolled. Patients' mean age was 8.9 years and 66.7% were male. At baseline, 66.7%, 75% and 91.7% of patients had a vIGA-AD score of 3 for cohorts 2–6, 7–11 and 12–17 years, respectively. Mean BSA (range) affected was 52.4% (36.0–90.0%), 42.0% (35.0–72.0%) and 33.9% (26.0–54.5%) for the three age cohorts, respectively. Mean Eczema Area and Severity Index scores were 30.2, 21.0 and 20.3, respectively. No-to-minimal tapinarof systemic exposure was observed, consistent with previous trials in adults. Mean tapinarof maximum plasma concentration (C max) at Day 1 was 2.4 ng/mL, and the median time to C max was approximately 3 h, for all patients. Approximately 25% of post-treatment plasma samples were below the quantifiable limit of the highly sensitive assay [<50 pg (10–12)/mL]. There was no correlation between tapinarof exposure (C max on Day 1) and baseline %BSA affected. Mean overall investigator-assessed LTS score was 0.1 (no irritation) at Weeks 1 and 4. Investigators assessed that the majority of patients had no irritation (LTS score of 0), including sensitive and intertriginous skin. The TEAEs were reported by eight patients (22%) and were all mild or moderate; one patient discontinued due to two unrelated TEAEs. One case of mild folliculitis and no contact dermatitis occurred. Most patients (87.5%) chose to enroll in the 48-week long-term extension trial. This is the first trial evaluating tapinarof in children down to 2 years of age. Tapinarof cream 1% QD demonstrated no-to-minimal systemic exposure in children with extensive AD, even when measured with a highly sensitive assay. There was a low incidence of TEAEs in patients with up to 90% BSA affected. Tapinarof cream was well tolerated, including sensitive and intertriginous skin areas. [ABSTRACT FROM AUTHOR]

Background The efficacy of albendazole therapy in patients with parenchymal neurocysticercosis (NCC) is suboptimal. Plasma levels of albendazole sulfoxide (ASOX), the active metabolite of albendazole, are highly variable among patients. We hypothesized that high ASOX plasma levels during albendazole therapy may be associated with an increased antiparasitic efficacy. Methods ASOX plasma levels were measured at treatment day 7 in 118 patients with parenchymal NCC enrolled in a treatment trial. The relationships between increasing ASOX plasma levels with the proportion of cysts resolved and the proportion of patients with complete cyst resolution (evaluated by 6-month brain magnetic resonance) were assessed. Results There was a trend toward a higher proportion of cysts resolved and a higher proportion of patients cured with increasing quartiles of ASOX plasma levels. In patients with 3 or more brain cysts, the regression analysis adjusted by the concomitant administration of praziquantel (PZQ) showed a 2-fold increase in the proportion of cysts resolved (risk ratio [RR], 1.98; 95% confidence interval [CI], 1.01–3.89; P =.048) and 2.5-fold increase in the proportion of patients cured (RR, 2.45; 95% CI,.94–6.36; P =.067) when ASOX levels in the highest vs the lowest quartile were compared. No association was found in patients with 1–2 brain cysts. Conclusions We suggest an association between high ASOX plasma levels and increased antiparasitic efficacy in patients with parenchymal NCC. Nonetheless, this association is also influenced by other factors including parasite burden and concomitant administration of PZQ. These findings may serve to individualize and/or adjust therapy schemes to avoid treatment failure. [ABSTRACT FROM AUTHOR]

Many systemic therapies used for moderate-to-severe atopic dermatitis (AD) have immunosuppressive properties and necessitate laboratory screening and monitoring, adding to the treatment burden. Previous dupilumab studies in adults, adolescents and children aged 6–11 years with moderate-to-severe AD showed no clinically meaningful adverse changes in laboratory parameters. Here we evaluate hematology and chemistry laboratory safety data for dupilumab-treated children aged 6 months to 5 years with moderate-to-severe atopic dermatitis. Patients aged 6 months to 5 years with inadequately controlled moderate-to-severe AD were enrolled in LIBERTY AD PRESCHOOL (NCT03346434 part B), a randomized, double-blind placebo-controlled phase 3 study. 162 patients were randomized to either dupilumab 200/300 mg every 4 weeks (q4w; N=83; baseline weight ≥5 <15 kg: 200 mg; ≥15 to <30 kg: 300 mg) or placebo (N=79) for 16 weeks. From Day –14, all patients initiated standardized treatment with low-potency topical corticosteroids. Laboratory data was collected at baseline, weeks 4 and 16. At baseline, mean (SD) counts of hematology parameters were similar in both treatment groups: haemoglobin (dupilumab: 129.4 gL−1 [12]; placebo: 127.2 gL−1 [11.4]), lymphocyte (dupilumab: 4.6×109 L−1 [1.8]; placebo: 4.5×109 L−1 [1.7]), basophil (dupilumab: 0.07×109 L−1 [0.03]; placebo: 0.07×109 L−1 [0.04]), platelet (dupilumab: 397.7×109 L−1 [103.2]; placebo: 385.6 × 109 L−1 [112.9]) and eosinophils (dupilumab: 1.1×109 L−1 [0.7]; placebo: 1.1×109 L−1 [0.7]). Mean (SD) haemoglobin count in the dupilumab (128.4×gL−1 [11]) and placebo groups (128.2×gL−1 [11.2]), lymphocyte count in the dupilumab (4.20×109 L−1 [2.06]) and placebo groups (4.29×109 L−1 [1.52]) and basophil count in the dupilumab (0.07×109 L−1 [0.04]) and placebo groups (0.06×109 L−1 [0.03]) remained with the normal reference range for this population at week 16. The mean change (SD) in platelet count at week 16 was −16.3×109 L−1 (78.5) in the dupilumab group and +17.4×109 L−1 (106.6) in the placebo group. In the dupilumab treatment group, the mean eosinophil count increased at week 4 (mean change from baseline [SD]; +0.48×109 L−1 [1.8]) and trended downward by week 16 (+0.31×109 L−1 [1.4]) while minimal changes were noted in the placebo group at week 4 (0.1×109 L−1 [0.7]) and week 16 (−0.2×109 L−1 [0.7]). The values for creatine kinase, alkaline phosphatase, lactate dehydrogenase, blood urea nitrogen, albumin and protein at week 16 remained within the normal reference range in all treatment groups. Two patients in the dupilumab 200/300 mg q4w arm of this study reported treatment-emergent adverse events of severe and moderate eosinophilia. Neither event was associated with clinical symptoms nor led to the discontinuation of the study treatment. No clinically meaningful changes in hematology and chemistry parameters in children aged 6 months to 5 years with moderate-to-severe AD were seen with 16 weeks of dupilumab treatment. These data demonstrate that, as with adults, adolescents and older children, routine laboratory monitoring is unnecessary in this younger population. Dupilumab was generally well tolerated with an acceptable safety profile. [ABSTRACT FROM AUTHOR]

Background. The enzyme-linked immunoelectrotransfer blot (EITB) assay is the reference serological test for neurocysticercosis (NCC). A positive result on EITB does not always correlate with the presence of active infections in the central nervous system (CNS), and patients with a single viable brain cyst may be EITB negative. Nonetheless, EITB antibody banding patterns appears to be related with the expression of 3 protein families of Taenia solium, and in turn with the characteristics of NCC in the CNS (type, stage, and burden of viable cysts). Methods. We evaluated EITB antibody banding patterns and brain imaging findings of 548 NCC cases. Similar banding patterns were grouped into homogeneous classes using latent class analysis. The association between classes and brain imaging findings was assessed. Results. Four classes were identified. Class 1 (patients negative or only positive to the GP50 band, related to the protein family of the same name) was associated with nonviable or single viable parenchymal cysticerci; class 2 (patients positive to bands GP42-39 and GP24, related to the T24-42 protein family, with or without anti-GP50 antibodies) was associated with intraparenchymal viable and nonviable infections; classes 3 and 4 (positive to GP50, GP42-39, and GP24 but also responding to low molecular weight bands GP21, GP18, GP14, and GP13, related to the 8 kDa protein family) were associated with extraparenchymal and intraparenchymal multiple viable cysticerci. Conclusions. EITB antibody banding patterns correlate with brain imaging findings and complement imaging information for the diagnosis of NCC and for staging NCC patients. [ABSTRACT FROM AUTHOR]

We present the discovery and spectroscopic confirmation with the European Southern Observatory New Technology Telescope (NTT) and Gemini South telescopes of eight new, and the rediscovery of two previously known, 6.0 < z < 6.5 quasars with zAB < 21.0. These quasars were photometrically selected without any morphological criteria from 1533 deg² using spectral energy distribution (SED) model fitting to photometric data from Dark Energy Survey (g, r, i, z, Y), VISTA Hemisphere Survey (J, H, K) and Wide-field Infrared Survey Explorer (W1, W2). The photometric data were fitted with a grid of quasar model SEDs with redshift-dependent Ly α forest absorption and a range of intrinsic reddening as well as a series of low-mass cool star models. Candidates were ranked using an SED-model-based χ²-statistic, which is extendable to other future imaging surveys (e.g. LSST and Euclid). Our spectral confirmation success rate is 100 per cent without the need for follow-up photometric observations as used in other studies of this type. Combined with automatic removal of the main types of non-astrophysical contaminants, the method allows large data sets to be processed without human intervention and without being overrun by spurious false candidates. We also present a robust parametric redshift estimator that gives comparable accuracy to Mg II and CO-based redshift estimators. We find two z ∼ 6.2 quasars with HII near zone sizes ≤3 proper Mpc that could indicate that these quasars may be young with ages ≲106-107 years or lie in over dense regions of the IGM. The z = 6.5 quasar VDES J0224-4711 has JAB = 19.75 and is the second most luminous quasar known with z ≥ 6.5. [ABSTRACT FROM AUTHOR]

Roflumilast is a selective, highly potent phosphodie-sterase 4 inhibitor under investigation as a nonsteroidal, once-daily cream for treatment of atopic dermatitis (AD). INTEGUMENT-1 (n = 654; NCT04773587) and INTEGUMENT-2 (n = 683; NCT04773600) were identical phase 3 randomized controlled trials conducted in patients with AD aged ≥6 years with baseline Eczema Area and Severity Index (EASI) score ≥5 and Validated Investigator Global Assessment-AD (vIGA-AD) score of mild or moderate. Patients were randomized 2 : 1 to apply once-daily roflumilast cream 0.15% or vehicle for 4 weeks. The primary efficacy endpoint was vIGA-AD Success [defined as score of 0 (clear) or 1 (almost clear) with 2-grade improvement from baseline] at Week 4. Secondary endpoints included 75% improvement in EASI (EASI-75). At Week 4, significantly more roflumilast-treated than vehicle-treated patients achieved vIGA-AD Success (INTEGUMENT-1: 32.2% vs. 15.2%; P < 0.0001; INTEGUMENT-2: 28.9% vs. 12.0%; P < 0.0001) and EASI-75 (INTEGUMENT-1: 43.2% vs. 22.0%; P < 0.0001; INTEGUMENT-2: 42.0% vs. 19.7%; P < 0.0001). Incidence of treatment-emergent adverse events (AEs) was low in both arms, with most assessed as mild to moderate in severity. No AE occurred in more than 3.5% of patients in either arm with low rates of application site pain in both the roflumilast- and vehicle-treated patients (INTEGUMENT-1: 2.1% vs. 0.5%; INTEGUMENT-2: 0.9% vs. 0.9%). Local tolerability was favorable with >90% of roflumilast-treated patients reporting no or mild sensation across arms in both trials at any timepoint. Once-daily roflumilast cream 0.15% improved AD across multiple efficacy endpoints while demonstrating favorable safety and tolerability in two phase 3 trials. [ABSTRACT FROM AUTHOR]

Background:  After decades of obscurity, Zika virus (ZIKV) has spread through the Americas since 2015 accompanied by congenital microcephaly and Guillain-Barré syndrome. Although these epidemics presumably involve transmission by Aedes aegypti, no direct evidence of vector involvement has been reported, prompting speculation that other mosquitoes such as Culex quinquefasciatus could be involved.Methods:  We detected an outbreak of ZIKV infection in southern Mexico in late 2015. Sera from suspected ZIKV-infected patients were analyzed for viral RNA and antibodies. Mosquitoes were collected in and around patient homes and tested for ZIKV.Results:  Of 119 suspected ZIKV-infected patients, 25 (21%) were confirmed by RT-PCR of serum collected 1-8 days after the onset of signs and symptoms including rash, arthralgia, headache, pruritus, myalgia, and fever. Of 796 mosquitoes collected, A. aegypti yielded ZIKV detection by RT-PCR in 15 of 55 pools (27.3%). No ZIKV was detected in C. quinquefasciatus ZIKV sequences derived from sera and mosquitoes showed a monophyletic relationship suggestive of a point source introduction from Guatemala.Conclusions:  These results demonstrate the continued, rapid northward progression of ZIKV into North America with typically mild disease manifestations, and implicate A. aegypti for the first time as a principal vector in North America. [ABSTRACT FROM AUTHOR]

As part of the Chandra Galactic Bulge Survey (GBS), we present a catalogue of optical sources in the GBS footprint. This consists of two regions centred at Galactic latitude b = 1°.5 above and below the Galactic Centre, spanning (l ? b) = (6° ? 1°). The catalogueconsists of two or more epochs of observations for each line of sight in ŕ, í and Hα filters. The catalogue is complete down to ŕ = 20.2 and í = 19.2 mag; the mean 5σ depth is ŕ = 22.5 and í = 21.1 mag. The mean root-mean-square residuals of the astrometric solutions is 0.04 arcsec. We cross-correlate this optical catalogue with the 1640 unique X-ray sources detected in Chandra observations of the GBS area, and find candidate optical counterparts to 1480 X-ray sources. We use a false alarm probability analysis to estimate the contamination by interlopers, and expect ~10 per cent of optical counterparts to be chance alignments. To determine the most likely counterpart for each X-ray source, we compute the likelihood ratio for all optical sources within the 4σ X-ray error circle. This analysis yields 1480 potential counterparts (~90 per cent of the sample). 584 counterparts have saturated photometry (ŕ ≤ 17, í ≤ 16), indicating these objects are likely foreground sources and the real counterparts. 171 candidate counterparts are detected only in the í band. These sources are good qLMXB and CV candidates as they are X-ray bright and likely located in the Bulge. [ABSTRACT FROM AUTHOR]

Background. The efficacy of current antiparasitic treatment for cerebral Taenia solium cysticercosis with either albendazole (ABZ) or praziquantel (PZQ) is suboptimal. A recent study demonstrated that combining these 2 antiparasitic drugs improves antiparasitic efficacy. We present here the parasiticidal efficacy data obtained during a previous phase II pharmacokinetic study that compared combined ABZ plus PZQ with ABZ alone. Methods. The study was a randomized, double-blinded, placebo-controlled phase II evaluation of the pharmacokinetics of ABZ (15 mg/k/d, for 10 days) and PZQ (50 mg/k/d, for 10 days) in intraparenchymal brain cysticercosis. Patients received the usual concomitant medications, including an antiepileptic drug (phenytoin or carbamazepine), dexamethasone, and ranitidine. Randomization was stratified by antiepileptic drug. Patients underwent safety laboratory evaluations at days 4, 7, and 11, as well as magnetic resonance (MR) imaging at 6 months to assess parasiticidal efficacy. Results. Thirty-two patients were included, 16 in each arm. All of them completed antiparasitic treatment and underwent follow-up brain MR imaging. Cysticidal efficacy was strikingly higher in the combined ABZ-plus-PZQ group than in the ABZalone group (proportion of cysts resolved, 78 of 82 [95%] vs 23 of 77 [30%] [relative risk {RR}, 3.18; 95% confidence interval {CI}, 2.08-4.88; P < .001]; patients with complete cyst clearance, 12 of 16 [75%] vs 4 of 16 [25%] [RR, 3.00; 95% CI, 1.23-7.34; P = .005]). Conclusions. The combination of ABZ plus PZQ is more effective in destroying viable brain cysticercosis cysts than ABZ alone. [ABSTRACT FROM AUTHOR]

We present the first results of a survey for high-redshift, z ≥ 6, quasars using izY multicolour photometric observations from the Dark Energy Survey (DES). Here we report the discovery and spectroscopic confirmation of the zAB, YAB = 20.2, 20.2 (M1450 = -26.5) quasar DES J0454-4448 with a redshift of z = 6.09±0.02 based on the onset of the Ly α forest and an H I near zone size of 4.1-1.2+1.1 proper Mpc. The quasar was selected as an i-band drop out with i-z=2.46 and zAB < 21.5 from an area of ~300 deg². It is the brightest of our 43 candidates and was identified for spectroscopic follow-up solely based on the DES i-z and z-Y colours. The quasar is detected by WISE and has W1AB = 19.68. The discovery of one spectroscopically confirmed quasar with 5.7 < z<6.5 and zAB ≤ 20.2 is consistent with recent determinations of the luminosity function at z ~ 6. DES when completed will have imaged ~5000 deg² to YAB = 23.0 (5θ point source) and we expect to discover 50-100 new quasars with z > 6 including 3-10 with z > 7 dramatically increasing the numbers of quasars currently known that are suitable for detailed studies. [ABSTRACT FROM AUTHOR]

We present a panoramic study of the Fornax dwarf spheroidal galaxy, using data obtained as part of the VLT Survey Telescope (VST) ATLAS Survey. The data presented here - a subset of the full survey - uniformly cover a region of 25 deg² centred on the galaxy, in g, r and i bands. This large area coverage reveals two key differences to previous studies of Fornax. First, data extending beyond the nominal tidal radius of the dwarf highlight the presence of a second distinct red giant branch population. This bluer red giant branch appears to be co-eval with the horizontal branch population. Secondly, a shell structure located approximately 1°.4 from the centre of Fornax is shown to be a mis-identified background overdensity of galaxies. This last result casts further doubt on the hypothesis that Fornax underwent a gas-rich merger in its relatively recent past. [ABSTRACT FROM AUTHOR]

The VLT Survey Telescope ATLAS survey is an optical ugriz survey aiming to cover 4700 deg² of the southern sky to similar depths as the Sloan Digital Sky Survey (SDSS). From reduced images and object catalogues provided by the Cambridge Astronomical Surveys Unit, we first find that the median seeing ranges from 0.8 arcsec FWHM (full width at halfmaximum) in i to 1.0 arcsec in u, significantly better than the 1.2-1.5 arcsec seeing for SDSS. The 5s mag limit for stellar sources is rAB = 22.7 and in all bands these limits are at least as faint as SDSS. SDSS and ATLAS are more equivalent for galaxy photometry except in the z band where ATLAS has significantly higher throughput. We have improved the original ESO magnitude zero-points by comparing m < 16 star magnitudes with the AAVSO Photometric All-Sky Survey in gri, also extrapolating into u and z, resulting in zero-points accurate to ±0.02 mag. We finally compare star and galaxy number counts in a 250 deg² area with SDSS and other count data and find good agreement. ATLAS data products can be retrieved from the ESO Science Archive, while support for survey science analyses is provided by the OmegaCAM Science Archive, operated by the Wide-Field Astronomy Unit in Edinburgh. [ABSTRACT FROM AUTHOR]

We announce the discovery of a new Galactic companion found in data from the ESO VST ATLAS survey, and followed up with deep imaging on the 4-m William Herschel Telescope. The satellite is located in the constellation of Crater (the Cup) at a distance of ∼170 kpc. Its half-light radius is rh = 30 pc and its luminosity is MV = −5.5. The bulk of its stellar population is old and metal poor. We would probably have classified the newly discovered satellite as an extended globular cluster were it not for the presence of a handful of blue loop stars and a sparsely populated red clump. The existence of the core helium burning population implies that star formation occurred in Crater perhaps as recently as 400 Myr ago. No globular cluster has ever accomplished the feat of prolonging its star formation by several Gyr. Therefore, if our hypothesis that the blue bright stars in Crater are blue loop giants is correct, the new satellite should be classified as a dwarf galaxy with unusual properties. Note that only 10°to the north of Crater, two ultrafaint galaxies Leo IV and Leo V orbit the Galaxy at approximately the same distance. This hints that all three satellites may once have been closely associated before falling together into the Milky Way halo. [ABSTRACT FROM AUTHOR]

This work investigated the roles of the tetraamine thermospermine (TSpm) by analysing its contribution to Arabidopsis basal defence against the biotrophic bacterium Pseudomonas viridiflava. The participation of polyamine oxidases (PAOs) in TSpm homeostasis and TSpm-mediated defence was also investigated. Exogenous supply of TSpm, as well as ectopic expression of the TSpm biosynthetic gene ACL5, increased Arabidopsis Col-0 resistance to P. viridiflava, while null acl5 mutants were less resistant than Col-0 plants. The above-mentioned increase in resistance was blocked by the PAO inhibitor SL-11061, thus demonstrating the participation of TSpm oxidation. Analysis of PAO genes expression in transgenic 35S::ACL5 and Col-0 plants supplied with TSpm suggests that PAO 1, 3, and 5 are the main PAOs involved in TSpm catabolism. In summary, TSpm exhibited the potential to perform defensive functions previously reported for its structural isomer Spm, and the relevance of these findings is discussed in the context of ACL5 expression and TSpm concentration in planta. Moreover, this work demonstrates that manipulation of TSpm metabolism modifies plant resistance to pathogens. [ABSTRACT FROM AUTHOR]

Background Hair loss is an unwelcome event at any age, but it can be particularly distressing for adolescents and their families. While androgenetic alopecia (AGA) is the most common form of hair loss in adults, little is known about its prevalence, clinical features and response to treatments in the paediatric population. Objectives To better characterize the causes of alopecia in a paediatric population. Methods We performed a retrospective chart review to identify all patients with hair loss seen in an academic paediatric dermatology practice at New York University over a 12-year period to better characterize the causes of alopecia in this population. We review the clinical and histological features, natural progression and associated laboratory abnormalities of AGA in 57 paediatric patients. Results AGA was identified as the most frequent cause of hair loss in adolescents and the second most common diagnosis overall. The male to female ratio was 2 : 1 and the average age at initial presentation with AGA was 14·8 years. Adolescent girls had diffuse thinning or thinning at the crown, and boys frequently presented with female pattern hair loss. When biopsies were performed, perifollicular inflammation was a common finding. A family history of AGA was reported in 83% of patients. Laboratory evaluation for androgens revealed polycystic ovarian syndrome in three girls and late-onset congenital adrenal hyperplasia in one boy. Conclusions AGA is the most common form of hair loss in adolescents, and can be the presenting sign of an underlying endocrine disorder. An accurate and timely diagnosis is essential for appropriate medical and psychosocial intervention when warranted. [ABSTRACT FROM AUTHOR]

We use the Spitzer Wide-area InfraRed Extragalactic Legacy Survey (SWIRE) to explore the specific star formation activity of galaxies and their evolution near the peak of the cosmic far-infrared (FIR) background at 70 and 160 μm. We use a stacking analysis to determine the mean FIR properties of well-defined subsets of galaxies at flux levels well below the FIR catalogue detection limits of SWIRE and other Spitzer surveys. We tabulate the contribution of different subsets of galaxies to the FIR background at 70 and 160 μm. These long wavelengths provide a good constraint on the bolometric obscured emission. The large area provides good constraints at low z and in finer redshift bins than previous work. At all redshifts we find that the specific FIR luminosity decreases with increasing mass, following a trend with . This is a more continuous change than expected from the De Lucia & Blaizot semi-analytic model suggesting modifications to the feedback prescriptions. We see an increase in the specific FIR luminosity by about a factor of ∼100 from and find that the specific FIR luminosity evolves as with for galaxies with . This is considerably steeper than the De Lucia & Blaizot semi-analytic model ( ). When separating galaxies into early and late types on the basis of the optical/IR spectral energy distributions we find that the decrease in specific FIR luminosity with stellar mass is stronger in early-type galaxies ( ), while late-type galaxies exhibit a flatter trend ( ). The evolution is strong for both classes but stronger for the early-type galaxies. The early types show a trend of decreasing strength of evolution as we move from lower to higher masses while the evolution of the late-type galaxies has little dependence on stellar mass. We suggest that in late-type galaxies we are seeing a consistently declining specific star formation rate through a common phenomenon, for example, exhaustion of gas supply, i.e. not systematically dependent on the local properties of the galaxy. [ABSTRACT FROM AUTHOR]

Flexible behaviors permit gregarious animals to exploit spatially and temporally favorable conditions for reproduction. Evening emergences of Brazilian free-tailed bats (Tadarida brasiliensis) in south-central Texas were recorded to determine changes in colony dynamics and to evaluate hypotheses associated with predator avoidance and seasonal energy demands. In 2007, median parturition date was 18 June and lactation lasted about 54 days. Juveniles commenced flight after 41 days, then continued to suckle for 2 weeks before being weaned. Onset of evening emergence was correlated with sunset, beginning, on average, 11.8 min after sunset (95% confidence interval 5 7.1, 16.6), which is later than reported in previous studies. Pregnant females emerged later than their roost mates, consistent with a predator avoidance hypothesis. Lactating females emerged after sunset, but earlier than other bats, consistent with the hypothesis that this is a period of high energy demand. Juveniles emerged later than adult females while they continued to be suckled, but emerged earlier as they matured and were weaned, suggesting a trade-off between predator avoidance and energy demands. Our observations indicate that evening emergence behavior of T. brasiliensis varies with environmental cues but is mediated by the energetic demands of reproduction. [ABSTRACT FROM AUTHOR]

Background. Neurocysticercosis (NCC) is a frequent cause of epilepsy worldwide. Compared with the more common parenchymal brain cysts, extraparenchymal infections are difficult to manage and have a poor prognosis. Serological assays are used to detect circulating Taenia solium antigens or anti-T. solium antibodies in serum or cerebrospinal fluid (CSF) samples. There are no guidelines on whether to use serum or CSF specimens for a particular assay. Methods. We obtained paired serum and CSF samples from 91 patients with NCC (48 had intraparenchymal NCC, and 43 had extraparenchymal NCC) for detection of antibodies, using an enzyme-linked immunotransfer blot (EITB) assay, and antigens, using a monoclonal antibody- based enzyme-linked immunosorbent assay (ELISA). Results. For the intraparenchymal NCC group, the EITB assay yielded more true-positive results for serum samples, and the ELISA yielded slightly more true-positive results for CSF samples than for serum samples, but none of these differences were statistically significant. Most patients with calcified NCC were antibody positive but antigen negative. For extraparenchymal disease, all samples were antibody positive, and all but 2 were antigen positive, with most samples containing high antigen levels. Conclusions. The sensitivity of antibody-detecting EITB assays is not increased through the use of CSF samples rather than serum samples. The antigen-detecting ELISA performed better for CSF samples than for serum samples, but for both specimen types it was less sensitive than the EITB assay. Active and inactive NCC are better differentiated from each other by the antigen-detecting ELISA, for both serum and CSF samples. High antigen levels suggest the presence of subarachnoid NCC. [ABSTRACT FROM AUTHOR]

We use the combinedgalform semi-analytical model of galaxy formation andgrasil spectrophotometric code to investigate the properties of galaxies selected via their submillimetre (submm) emission. The fiducial model we use has previously been shown to fit the properties of local Ultra-Luminous Infrared Galaxies, as well as the number counts of faint submm galaxies. Here, we test the model in more detail by comparing the SEDs and stellar, dynamical, gas and halo masses of submm galaxies against observational data. We precisely mimic the submm and radio selection function of the observations and show that the predicted far-infrared properties of model galaxies with and are in good agreement with observations. Although the dust emission model does not assume a single dust temperature, the far-infrared SEDs are well described by single component modified blackbody spectrum with characteristic temperature , in good agreement with observations. We also find evidence that the observations may have uncovered evolution in the far-infrared–radio relation in ULIRGs out to . We show that the predicted redshift distribution of submm galaxies provides a reasonable fit to the observational data with a median redshift . The radio-selected subset of submm galaxies are predicted to make up approximately 75 per cent of the population and peak at , in a reasonable agreement with the observed radio detected fraction and redshift distribution. However, the predicted K band and mid-infrared (3–8 μm) flux densities of the submm galaxies [and Lyman-Break Galaxies (LBGs)] are up to a factor of 10× fainter than observed. We show that including the stellar thermally pulsating asymptotic giant branch phase in the stellar population models does not make up for this deficit. This discrepancy may indicate that the stellar masses of the submm galaxies in the model are too low: , while observations suggest more massive systems, . However, if the predicted K- and 3–8-μm extinctions in the model could be dramatically reduced, then this would reduce, but not eliminate, this discrepancy. Finally, we discuss the potential modifications to the models which may improve the fit to the observational data, as well as the new observational tests which will be made possible with the arrival of new facilities, such as Submillimetre Common-User Bolometer Array2. [ABSTRACT FROM AUTHOR]

We investigate the clustering of galaxies selected in the 3.6 μm band of the Spitzer Wide-area Infrared Extragalactic (SWIRE) legacy survey. The angular two-point correlation function is calculated for 11 samples with flux limits of S3.6≥ 4–400 μJy, over an 8 deg2 field. The angular clustering strength is measured at >5σ significance at all flux limits, with amplitudes of A= (0.49–29) × 10−3 at 1°, for a power-law model, Aθ−0.8. We estimate the redshift distributions of the samples using phenomological models, simulations and photometric redshifts, and so derive the spatial correlation lengths. We compare our results with the Galaxies In Cosmological Simulations (GalICS) models of galaxy evolution and with parametrized models of clustering evolution. The GalICS simulations are consistent with our angular correlation functions, but fail to match the spatial clustering inferred from the phenomological models or the photometric redshifts. We find that the uncertainties in the redshift distributions of our samples dominate the statistical errors in our estimates of the spatial clustering. At low redshifts (median z≤ 0.5), the comoving correlation length is approximately constant, Mpc, and then decreases with increasing redshift to a value of 2.9 ± 0.3 h−1 Mpc for the faintest sample, for which the median redshift is z∼ 1. We suggest that this trend can be attributed to a decrease in the average galaxy and halo mass in the fainter flux-limited samples, corresponding to changes in the relative numbers of early- and late-type galaxies. However, we cannot rule out strong evolution of the correlation length over . [ABSTRACT FROM AUTHOR]

We analyse the first publicly released deep field of the UK Infrared Deep Sky Survey (UKIDSS) Deep eXtragalactic Survey to identify candidate galaxy overdensities at across ∼1 deg2 in the ELAIS-N1 field. Using and colours, we identify and spectroscopically follow up five candidate structures with Gemini/Gemini Multi-Object Spectrograph and confirm that they are all true overdensities with between five and 19 members each. Surprisingly, all five structures lie in a narrow redshift range at , although they are spread across 30 Mpc on the sky. We also find a more distant overdensity at in one of the spectroscopic survey regions. These five overdense regions lying in a narrow redshift range indicate the presence of a supercluster in this field and by comparing with mock cluster catalogues from N-body simulations we discuss the likely properties of this structure. Overall, we show that the properties of this supercluster are similar to the well-studied Shapley and Hercules superclusters at lower redshift. [ABSTRACT FROM AUTHOR]

We present the initial results from our search for high-redshift, , quasars using near-infrared (near-IR) data from the UKIRT Infrared Deep Sky Survey Large Area Survey. Our analysis of 106 deg2 of sky from Data Release 1 has resulted in the discovery of ULAS J020332.38+001229.2, a luminous quasar at . Following candidate selection from the combined IR and optical catalogue data and stacking of multiple epoch Sloan Digital Sky Survey (SDSS) data, we have obtained optical spectroscopy for the only two quasar candidates. The Very Large Telescope FORS2 spectrum of ULAS J020332.38+001229.2 shows broad Lyα+ N v 1240 emission at ∼8350 Å and an abrupt continuum break due to absorption by the Lyα forest. The quasar is not present in the SDSS DR5 catalogue and the continuum spectral index of is redder than a composite of SDSS quasars at similar redshifts . The discovery of one quasar in ∼100 deg2 in a complete sample within our selection criteria down to a median depth of (7σ) is consistent with existing SDSS results. We describe our survey methodology, including the use of optical data from the SDSS and the highly effective procedures developed to isolate the very small surface density of high-probability quasar candidates. [ABSTRACT FROM AUTHOR]

Background. Cases of pyomyositis and myositis have been increasing in frequency at Texas Children's Hospital (Houston) since 2000. The increase appears to correlate with the emergence of community-acquired methicillin-resistant Staphylococcus aureus (MRSA). Methods. The medical records of patients with pyomyositis and myositis hospitalized at Texas Children's Hospital during the period from January 2000 through December 2005 were reviewed. Available S. aureus isolates were obtained for susceptibility testing, to determine the presence of pvl (lukS-PV and lukF-PV), and for pulsed-field gel electrophoresis analysis. Results. Forty-five previously healthy children with bacterial pyomyositis or myositis were analyzed. The causes were S. aureus (in 57.8% of children) and Streptococcus pyogenes (in 2.2%); 40.0% of children had negative culture results. The number of cases increased between 2000 and 2005, primarily as a result of an increase in the prevalence of community-acquired MRSA. The mean patient age was 5.5 years (range, 0.06-15 years). The thigh (40.0% of children) and pelvis (28.9%) were the most commonly affected sites. The mean abscess diameter was 3.5 cm. Eighteen children required at least 1 muscle drainage procedure. Of the 24 available S. aureus isolates (15 community-acquired MRSA isolates and 9 community-acquired, methicillin-susceptible S. aureus [MSSA] isolates), 16 were found to be USA300 by pulsed-field gel electrophoresis, and 17 carried pvl. Patients with community-acquired MRSA, USA300, and/or pvl-positive strains required more drainage procedures than did those with community-acquired MSSA, non-USA300, and/or pvl-negative strains (81% vs. 40% [P=.05], 82% vs. 29% [P=.02], and 81% vs. 38% [P=.07], respectively). Conclusions. Community-acquired MRSA is an increasing cause of pyomyositis and myositis in children. Community-acquired MRSA, USA300, pvl-positive S. aureus isolates caused more severe disease than did community-acquired MSSA, non-USA300, and pvl-negative isolates, respectively. [ABSTRACT FROM AUTHOR]

We construct rest-frame luminosity functions (LFs) at 3.6, 4.5, 5.8, 8 and 24 μm over the redshift range for galaxies and for optical quasi-stellar objects (QSOs), using optical and infrared (IR) data from the Spitzer Wide-area Infrared Extragalactic (SWIRE) Survey. The 3.6- and 4.5-μm galaxy LFs show evidence for moderate positive luminosity evolution up to , consistent with the passive ageing of evolved stellar populations. Their comoving luminosity density was found to evolve passively, gradually increasing out to but flattening, or even declining, at higher redshift. Conversely, the 24-μm galaxy LF, which is more sensitive to obscured star formation and/or active galactic nuclei (AGN) activity, undergoes strong positive evolution, with the derived IR energy density and star formation rate (SFR) density with and the majority of this evolution occurring since . Optical QSOs, however, show positive luminosity evolution in all bands, out to the highest redshifts . Modelling as gave at at and stronger evolution at the longer wavelengths (5.8, 8 and ), of . Comparison of the galaxy LFs to predictions from a semi-analytic model based on cold dark matter (CDM) indicates that an initial mass function (IMF) skewed towards higher mass star formation in bursts compared to locally be preferred. As a result, the currently inferred massive SFRs in distant submm sources may require substantial downwards revision. [ABSTRACT FROM AUTHOR]

Summary: Twenty-five patients with calcified neurocysticercosis (two to four intraparenchymal brain calcifications) were asked to have a non-contrasted computed tomography (CT) scan of the thighs to determine the frequency of muscle calcifications detected by this technique. Thirteen (52%) showed one or more muscle calcifications. The numbers of calcifications in the thighs and the brain were not correlated. Patients with a positive CT scan for muscle calcifications were also examined by X-rays to compare both methods. Only 6 of 13 had visible calcifications on X-ray. Thigh CT scans can demonstrate muscle calcifications in a significant proportion of patients with calcified neurocysticercosis. [Copyright &y& Elsevier]

Background. Primary pneumonia and metastatic pulmonary infection have become more common in patients with invasive community-acquired Staphylococcus aureus disease at Texas Children's Hospital (TCH; Houston). Methods. In this study, we sought to describe pulmonary involvement in children with community-acquired S. aureus invasive infection and to determine whether the presence of genes encoding Panton-Valentine leukocidin (PVL) (luk-S-PV and luk-F-PV) and collagen adhesin (cna) is correlated with pulmonary manifestations. Patients with invasive staphylococcal infections admitted to TCH between 1 August 2001 and 30 June 2004 were studied. Chest imaging and postmortem examination reports were reviewed. Isolates were tested for the presence of genes encoding PVL and collagen adhesin by PCR. Results. A total of 47 of 70 patients with community-acquired methicillin-resistant S. aureus (MRSA) infection had abnormal pulmonary imaging findings, compared with 12 of 43 patients with community-acquired methicillin-susceptible S. aureus (MSSA) infection (P < .001). Pneumonia and/or empyema, in addition to septic emboli, were the most common findings. Metastatic pulmonary disease occurred more frequently among patients with osteomyelitis. Severe necrotizing pneumonia was present in 3 children coinfected with influenza and parainfluenza virus. The presence of genes encoding PVL was investigated in 67 MRSA and 36 MSSA isolates. Abnormal chest imaging findings were observed for 51 of 80 patients with PVL-positive isolates, compared with 2 of 23 patients with PVL-negative isolates (P< .001). Only 2 isolates (both of which were MSSA) from patients with abnormal chest radiograph findings carried cna. PVL remained independently associated with abnormal chest imaging findings in patients with secondary pneumonia in a multivariate analysis (P = .03). Conclusions. Pulmonary involvement is commonly observed in patients with invasive community-acquired S. aureus infections. Community-acquired MRSA may cause primary community-acquired pneumonia, as well as metastatic pulmonary disease. The presence of genes encoding PVL is highly associated with pulmonary involvement by S. aureus. [ABSTRACT FROM AUTHOR]

Background. Methicillin-resistant Staphylococcus aureus (MRSA) isolates are increasingly frequent causes of skin and soft-tissue infections or invasive infections in many communities. Methods. Prospective surveillance for community-acquired S. aureus infections at Texas Children's Hospital was initiated on 1 August 2001. Infections meeting the definition of community-acquired were identified. De- mographic and clinical data were collected. Antibiotic susceptibilities, including inducible resistance to macrolide, lincosamide, and streptogramin B (MLSB), were determined in the clinical microbiology laboratory with the methodology of the NCCLS. All data were entered into a computer database. Data were analyzed by x2 tests. Results. From 1 August 2001 to 31 July 2004, the percentage of community-acquired S. aureus isolates that were methicillin resistant increased from 71.5% (551 of 771 isolates) in year 1 to 76.4% (1193 of 1562 isolates) in year 3 (P = .008). The number of both community-acquired MRSA (CA-MSRA) isolates and community- acquired methicillin-susceptible S. aureus (CA-MSSA) isolates increased yearly, but the rate of increase was greater for the CA-MRSA isolates. Among the CA-MRSA isolates, 2542 (95.6%) were obtained from children with skin and soft-tissue infections, and 117 (4.4%) were obtained from children with invasive infections. Overall, 62% of children with CA-MRSA isolates and 53% of children with CA-MSSA isolates were admitted to the hospital (P = .0001). The rate of clindamycin resistance increased significantly for both CA-MRSA isolates (P = .003) and CA-MSSA isolates (P = .00003) over the 3 years. MLSB inducible resistance was found in 27 (44%) of 62 din- damycin-resistant CA-MSSA isolates, compared with 6 (4.5%) of 132 clindamycin-resistant CA-MRSA isolates (P.c .000001). Conclusions. CA-MRSA isolates account for an increasing percentage and number of infections at Texas Children's Hospital. Clindamycin resistance increased among community-acquired S. aureus isolates. Community surveillance of community-acquired S. aureus infections is critical to determine the appropriate empiric antibiotic treatment for either local or invasive infections. [ABSTRACT FROM AUTHOR]

We present the multiwavelength properties and catalogue of the 15 μm and 1.4 GHz radio sources detected in the European Large AreaISOSurvey (ELAIS) areas N1 and N2. Using the optical data from the Wide Field Survey we use a likelihood ratio method to search for the counterparts of the 1056 and 691 sources detected at 15 μm and 1.4 GHz, respectively, down to flux limits ofand. We find that∼92 per cent of the 15 μmELAISsources have an optical counterpart down to. All mid-infrared (IR) sources with fluxeshave an optical counterpart. The magnitude distribution of the sources shows a well-defined peak at relatively bright magnitudes. The mid-IR-to-optical and radio-to-optical flux diagrams are presented and discussed in terms of actual galaxy models. About 15 per cent of the sources are bright galactic stars; of the extragalactic objects∼65 per cent are compatible with being normal or starburst galaxies and∼25 per cent active galactic nuclei (AGNs). Objects with mid-IR-to-optical fluxes larger than 100 are found, comprising∼20 per cent of the sample. We suggest that that these sources are highly obscured luminous and ultraluminous starburst galaxies and AGNs. [ABSTRACT FROM AUTHOR]

We present the final analysis of the European Large AreaInfrared Space Observatory(ISO) Survey (ELAIS) 15-μm observations, carried out with the ISO Camera (ISOCAM) instrument on board theISO.The data-reduction method, known as the Lari Method, is based on a mathematical model of the behaviour of the detector and was specifically designed for the detection of faint sources in ISOCAM/ISO Photopolarimeter (ISOPHOT) data. The method is fully interactive and leads to very reliable and complete source lists.The resulting catalogue includes 1923 sources detected with signal-to-noise ratio ofin the 0.5–100 mJy flux range and over an area of 10.85 deg2 split into four fields, making it the largest non-serendipitous extragalactic source catalogue obtained to date from theISOdata.This paper presents the concepts underlying the data-reduction method together with its latest enhancements. The data-reduction process, the production and basic properties of the resulting catalogue are discussed. The catalogue quality is assessed by means of detailed simulations, optical identifications and comparison with previous analyses. [ABSTRACT FROM AUTHOR]

We present a cross-correlation of the European Large AreaInfrared Space Observatory(ISO) survey (ELAIS) with the ELAIS Deep X-ray Survey of the N1 and N2 fields. There are sevenChandrapoint sources with matches in the ELAIS Final Analysis 15-μm catalogue, out of a total of 28 extragalacticISOsources present in theChandrafields. Five of these are consistent with active galactic nuclei (AGN) giving an AGN fraction of∼19 per cent in the 15-μm flux range 0.8–6 mJy. We have co-added the hard X-ray fluxes of the individually undetectedISOsources and find a low significance detection consistent with star formation in the remaining population. We combine our point source cross-correlation fraction with theXMM–Newtonobservations of the Lockman Hole andChandraobservations of theHubble Deep FieldNorth to constrain source count models of the mid-infrared galaxy population. The low dust-enshrouded AGN fraction in ELAIS implied by the number of cross-identifications between the ELAIS mid-infrared sample and theChandrapoint sources is encouraging for the use of mid-infrared surveys to constrain the cosmic star formation history, provided there are not further large undetected populations of Compton-thick AGN. [ABSTRACT FROM AUTHOR]

We present a combined galaxy–quasar approach to template-fitting photometric redshift techniques and show the method to be a powerful one. The code (I mpZ) is presented, developed and applied to two spectroscopic redshift catalogues, namely the Isaac Newton Telescope Wide-Angle Survey ELAIS N1 and N2 fields and the Chandra Deep Field North. In particular, optical size information is used to improve the redshift determination. The success of the code is shown to be very good, with constrained to within 0.1 for 92 per cent of the galaxies in our sample. The extension of template fitting to quasars is found to be reasonable, with constrained to within 0.25 for 68 per cent of the quasars in our sample. Various template extensions into the far-ultraviolet are also tested. [ABSTRACT FROM AUTHOR]

ABSTRACT We present an analysis of two deep (75 ks) Chandra observations of the European Large Area Infrared Space Observatory (ISO) Survey (ELAIS) fields N1 and N2 as the first results from the ELAIS deep X-ray survey. This survey is being conducted in well-studied regions with extensive multiwavelength coverage. Here we present the Chandra source catalogues along with an analysis of source counts, hardness ratios and optical classifications. A total of 233 X-ray point sources are detected in addition to two soft extended sources, which are found to be associated with galaxy clusters. An overdensity of sources is found in N1 with 30 per cent more sources than N2, which we attribute to large-scale structure. A similar variance is seen between other deep Chandra surveys. The source count statistics reveal an increasing fraction of hard sources at fainter fluxes. The number of galaxy-like counterparts also increases dramatically towards fainter fluxes, consistent with the emergence of a large population of obscured sources. [ABSTRACT FROM AUTHOR]

R1 and R2 elements are non-LTR retrotransposons that insert specifically into the 28S rRNA genes of arthropods. The process of concerted evolution of the rDNA locus should give rise to rapid turnover of these mobile elements compared to elements that insert at sites throughout a genome. To estimate the rate of R1 and R2 turnover we have examined the insertion of new elements and elimination of old elements in the Harwich mutation accumulation lines of Drosophila melanogaster, a set of inbred lines maintained for >350 generations. Nearly 300 new insertion and elimination events were observed in the 19 Harwich lines. The retrotransposition rate for R1 was 18 times higher than the retrotransposition rate for R2. Both rates were within the range previously found for retrotransposons that insert outside the rDNA loci in D. melanogaster. The elimination rates of R1 and R2 from the rDNA locus were similar to each other but over two orders of magnitude higher than that found for other retrotransposons. The high rates of R1 and R2 elimination from the rDNA locus confirm that these elements must maintain relatively high rates of retrotransposition to ensure their continued presence in this locus. [ABSTRACT FROM AUTHOR]

In evaluating carbon flux in coastal and oceanic waters off central Chile (~36°S), the grazing pressure by copepod size-assemblages and the gravitational flux from the surface layer were estimated during two contrasting seasons: spring upwelling (October 1998) and winter (July 1999) periods. Grazing pressure upon phytoplankton biomass was small (<5%) during both periods at all stations. It was, however, an important proportion of primary production at the coast during the spring (17–43%) but minimal in winter (<5%) while, at the oceanic station, it was significant during both seasons (13–46%). Similarly, the downward flux of particulate organic carbon was a significant percentage of primary production at the coast during the spring (31%) and less so in winter (15%); at the oceanic station, it was a higher fraction during both seasons (46–47%). Copepod pellets were only a minor component of the faecal flux, suggesting that they were rapidly recycled in the water column. The seasonal differences in these carbon fluxes in the coastal upwelling zone were related directly to the larger quantities of organic matter in the water column during the spring upwelling period, including higher chlorophyll a concentrations and primary production rates. During the winter, the particulate organic carbon appears to be mainly recycled in the water column. In the oceanic zone, in contrast to what is expected, a large percentage of the primary production appears to be exported during both periods, though consumption by copepod assemblages was also important, suggesting significant horizontal carbon export from the coast to the open ocean. [ABSTRACT FROM PUBLISHER]

Investigates the dynamics of the mobile elements R1 and R2 in the rDNA locus of Drosophila simulans. Variants generated during the target-primed reverse transcription mechanism; rDNA loci of individual X chromosomes in a population of Drosophila simulans; Suggestion of a higher frequency of R1 and R2 retrotransposition.

The evolution of physicochemical parameters, and the most important microbial groups, were determined for the following three batches of ‘Cameros’ goat's milk cheese during ripening: Batch R elaborated with raw milk, Batch RS elaborated with raw milk and with the addition of a starter culture, and Batch PS elaborated with pasteurized milk and with the addition of the same culture. No differences in total solids (TS) or in the content of NaCl, fat and total nitrogen (expressed as percentages of TS) were found during the ripening. The pH, fat acidity and non-protein nitrogen (NPN, expressed as a percentage of TN) showed significant differences between the batches. The inoculated batches showed the fastest drop in pH at the beginning of the ripening period, but the cheeses of Batch R showed a higher degree of lipolysis and proteolysis. The addition of a starter influenced the microbiological quality of the cheeses. Differences in the counts of Enterobacteriaceae and faecal coliforms were found between Batches R and RS after 15 days. Staphylococcus aureus increased in number during the early period of ripening and attained a population above 6 log cfu g-1 in Batch R in the period from 5 to 10 days. However, enterotoxins were not detected in this Batch. Batch R showed lower values of lactic acid bacteria at the beginning of the ripening period, but no significant differences were found between batches in the period from 5 to 15 days of ripening. At the beginning of the ripening, Lactococcus was the main lactic acid bacteria, with L. lactis lactis being predominant. After 15 days, the lactic acid bacteria counts decreased in the three batches, especially in the cheeses of Batch PS (only 2·2 log cfu g-1 was found at 60 days), as lactococci (the only lactic acid bacteria present in Batch PS) are incapable of growing under the conditions found in cheeses at the end of their ripening period. At this time, Lactobacillus was the... [ABSTRACT FROM AUTHOR]

Discusses the use of epidemiological data on neurocysticercosis in Peru to calculate the burden of disease. Association of cysticercosis to higher epilepsy rates in developing countries; Adult seizure disorder rate among seropositive and seronegative persons; Average prevalence rates in areas of endemicity.

The present study was performed in order to discern the effects of propylthiouracil (PTU) on ethanol and/or protein deficiency-mediated liver histological changes and liver Fe, Zn, Cu and Mn alterations in male adult Wistar rats. The study was performed on 64 animals divided into eight groups, fed with the Lieber-DeCarli control, 36% ethanol-2Tenenrife, Canary Islands, Spain protein-and 36% ethanol-2% protein-containing diets, without and with PTU, respectively PTU was administered at a concentration of 0.05%, an amount which rendered the animals hypothyroid. Two further groups of 5 animals each, with and without PTU respectively, were allowed to consume the control diet ad libitum. Animals treated with PTU showed significantly less fibrosis, but more fat, than animals without PTU. Liver fibrosis was inversely correlated with liver zinc, liver content of this element being higher in the PTU-treated and the ethanol or protein deficiency groups PTU also reversed ethanol-mediated hepatocyte ballooning and also led to a reduction in nuclear areas. [ABSTRACT FROM PUBLISHER]

A hypermetabolic state with increased oxygen consumption has been described in alcoholic hepatitis, playing a major role in ethanol-induced liver damage. Based on its ability to decrease oxygen consumption, propylthiouracil (PTU) has been proposed as a therapeutic agent in this context. On the other hand, several muscle changes have been described in hypothyroidism. Including both atrophy and hypertrophy of muscle fibres. The aim of this experimental study was to analyse the effects of PTU on the alcohol-induced changes in muscle fibre size and proportion, also taking into account the presence or absence of protein deficiency. The study was performed on 64 male Wistar rats divided into eight groups, fed with: (1) Lieber-DeCarli control diet: (2) an isocaloric 36% ethanol-containing diet; (3) an isocaloric 2% protein-containing diet: (4) an isocaloric 36% ethanol 2% protein-containing diet, without and with PTU, respectively. Right gastrocnemius muscle was removed 2 months later and histochemical and morphometric studies were performed Type lIb fibre atrophy was observed both in the alcoholic and protein-deficient animals, but not in the PTU-treated animals. The combination of protein deficiency and ethanol led to a more marked type IIb atrophy, with PTU reversing this effect. Malnutrition led to a decrease in type I fibre diameter; ethanol and PTU caused an increase in its size and PTU reversed the effect of protein deficiency. Proportion of type IIb fibres decreased in the three experimental groups without PTU with respect to the control, especially in the alcoholic protein-deficient animals. PTU-treated animals, especially those fed a low-protein diet, showed a more marked reduction in type IIb fibre proportion than that presented by the groups without PTU. However, an increase in type I fibre proportion was observed in the PTU-treated animals, especially marked in those fed a low-protein diet Thus, PTU seems to ameliorate ethanol-induced changes on type IIb muscle fibres. [ABSTRACT FROM PUBLISHER]