Differential expression of mutant and normal beta T3 receptor alleles in kindreds with generalized resistance to thyroid hormone.
Thyroid hormone resistance (THR) is primarily an autosomal dominant inherited disease characterized by resistance of pituitary and peripheral tissues to the action of thyroid hormone. We investigated whether the heterogeneous phenotypic features that occur not only among kindreds but also within the same kindred might be due to the expression of differing ratios of mutant and normal receptors in tissues. Using an allele-specific primer extension method, we determined the relative expression of normal and mutant mRNAs from the fibroblasts of affected and unaffected members of two kindreds with TRH: A-H and N-N. While two affected members of A-H, as expected, had nearly equal amounts of normal and mutant hTR beta mRNA, two other members had mutant mRNA levels that accounted for at least 70% of the hTR beta mRNA. Phenotypic variability within and between kindreds with generalized resistance to thyroid hormone GRTH may be due to this differential expression of the mutant and wild type mRNA. Furthermore, when several clinical parameters of THR were compared in several affected members from two kindreds with GRTH, we found that two cases in one kindred exhibited a high mutant-to-normal hTR beta ratio and had considerably more bone resistance during their development. In certain kindreds with THR, differing ratios of normal and mutant hTR receptors may be age and growth related and may account for the reported attenuation of phenotypic symptoms with age.


Visual asymmetries for relative depth judgments in a three-dimensional space.
Our ability to process information about an object's location in depth varies along the horizontal and vertical axes. These variations reflect functional specialisation of the cerebral hemispheres as well as the ventral/dorsal visual streams for processing stimuli located in near and far space. Prior research has demonstrated visual field superiorities for processing near space in the lower and right hemispaces and for far space in the upper and left hemispaces. No research, however, has directly tested whether the functional specialisation of the visual fields actually makes objects look closer when presented in the lower or right visual fields. To measure biases in the perception of depth, we employed anaglyph stimuli where participants made closer/further judgments about the relative location of two spheres in a three-dimensional virtual space. We observed clear processing differences in this task where participants perceived the right and lower spheres to be closer and the left and upper spheres to be further away. Furthermore, no relationship between the horizontal and vertical dimensions was observed suggesting separate cognitive/neural mechanisms. Not only does this methodology clearly demonstrate differences in perceived depth across the visual field, it also opens up many possibilities for studying functional asymmetries in three-dimensional space.


HIV type 1 Tat inhibits tumor necrosis factor alpha-induced repression of tumor necrosis factor receptor p55 and amplifies tumor necrosis factor alpha activity in stably tat-transfected HeLa Cells.
The human immunodeficiency virus type 1 (HIV-1) Tat protein is a key regulatory protein in the HIV-1 replication cycle. Tat interacts with cellular transcriptional factors and cytokines, such as tumor necrosis factor (TNF-alpha), and alters the expression of a variety of genes in HIV-1-infected and noninfected cells. To further elucidate the mechanisms by which HIV-1 Tat amplifies the activity of TNF-alpha, we transfected the HIV-1 tat gene into an epithelial (HeLa) cell line. We observed that Tat-expressing cells had increased NF-kappa B-dependent trans-activational activity due to enhanced NF-kappa B--DNA binding in response to TNF-alpha treatment. Tumor necrosis factor receptor (TNFR) p55 was the prominent receptor, as neutralizing antibodies to TNFR p55, but not to TNFR p75, blocked TNF-alpha-mediated NF-kappa B activation. Furthermore, tat-transfected cells were more sensitive to TNF-alpha-induced cytotoxicity and only the neutralizing antibodies to TNFR p55 completely protected the cells. To determine whether TNFR p55 was involved in amplification of cellular response to TNF-alpha by HIV-1 Tat, we investigated the effect of TNF-alpha on TNFR p55 expression in the tat-transfected cells. TNF-alpha treatment resulted in a reduction in both TNFR p55 mRNA and protein levels in the control cells but not in the tat-transfected cells as determined with Northern blot and Western blot analyses, respectively. Our results indicate that HIV-1 Tat may inhibit TNF-alpha-induced repression of TNFR p55 and thereby amplify TNF-alpha activity in these stably transfected cells.


Diversification in the northern neotropics: mitochondrial and nuclear DNA phylogeography of the iguana Ctenosaura pectinata and related species.
While Quaternary climatic changes are considered by some to have been a major factor promoting speciation within the neotropics, others suggest that much of the neotropical species diversity originated before the Pleistocene. Using mitochondrial and nuclear sequence data, we evaluate the relative importance of Pleistocene and pre-Pleistocene events within the evolutionary history of the Mexican iguana Ctenosaura pectinata, and related species. Results support the existence of cryptic lineages with strong mitochondrial divergence (> 4%) among them. Some of these lineages form zones of secondary contact, with one of them hybridizing with C. hemilopha. Evolutionary network analyses reveal the oldest populations of C. pectinata to be those of the northern and southern Mexican coastal regions. Inland and mid-latitudinal coastal populations are younger in age as a consequence of a history of local extinction within these regions followed by re-colonization. Estimated divergence times suggest that C. pectinata originated during the Pliocene, whereas geographically distinct mitochondrial DNA lineages first started to diverge during the Pliocene, with subsequent divergence continuing through the Pleistocene. Our results highlight the influence of both Pliocene and Pleistocene events in shaping the geographical distribution of genetic variation within neotropical lowland organisms. Areas of high genetic diversity in southern Mexico were detected, this finding plus the high levels of genetic diversity within C. pectinata, have implications for the conservation of this threatened species.


Chromatic aberrations of radial gradient-index lenses. I. Theory.
Chromatic effects of radial gradient-index materials have been analyzed, and several important conclusions have been derived in terms of material dispersion data. The use of Buchdahl dispersion data, both for base glass materials and ion-exchange pairs, provides some simple relationships for chromatic aberration and helps in selecting suitable materials for producing achromatic radial gradient-index lenses.


Association of statin therapy with blood pressure control in hypertensive hypercholesterolemic outpatients in clinical practice.
Some clinical evidence revealed that statins, apart from lowering cholesterol levels, also have an antihypertensive effect. Our aim was to evaluate the existence of a possible association of statin therapy with blood pressure (BP) control in clinical practice. Patients attending a hypertension/dyslipidemia clinic were prospectively evaluated. Those patients with a diagnosis of stage 1 hypertension and hypercholesterolemia who consented to participate were included in the study, either in the statin group (when taking a statin) or in the control group (when not taking a statin). Exclusion criteria included dementia, pregnancy, or breastfeeding, and history or evidence of stage 2 hypertension. Detailed clinical information was prospectively obtained from medical records. A total of 110 hypertensive patients were assigned to the study (82 in the statin group and 28 in the control group). Although there were no significant differences (P > 0.05) in both groups concerning gender, body mass index, antihypertensive pharmacotherapy, and serum levels of high-density lipoprotein cholesterol and triglycerides, a higher BP control was observed in the statin group (P = 0.002). Significantly lower systolic BP (-6.7 mmHg, P = 0.020) and diastolic BP (-6.4 mmHg, P = 0.002) levels were reported in the statin group. Serum levels of low-density lipoprotein were also significantly lower in the statin group (P < 0.001). This observational study detected an association of statin therapy with BP control in hypertensive hypercholesterolemic patients in clinical practice. These findings raise the possibility that statin therapy may be useful for BP control in the studied population.


One-step large-scale highly active g-C3N4 nanosheets for efficient sunlight-driven photocatalytic hydrogen production.
The development of highly active, cost-effective, environmentally friendly and stable g-C3N4 based photocatalysts for H2 evolution is one of the most anticipated potential pathways for future hydrogen utilization. Herein, a facile gaseous bubble template approach was designed to prepare large-scale thin g-C3N4 nanosheets (g-C3N4 NSs) using melamine and ammonium sulphate as the bubble template. Through distinctive structural improvements for a large bandgap, excellent electron mobility, prolonged lifetime of the photogenerated charge carriers and a high specific surface area with highly accessible potential reaction sites, the as-synthesized g-C3N4 NSs demonstrated a high photocatalytic hydrogen evolution rate of 9871 μmol h-1 g-1 and efficient photocatalytic degradation of Rhodamine B (RhB) and phenol under simulated solar light irradiation.


Kin discrimination and demography modulate patterns of sexual conflict.
Recent years have seen an explosion of interest in the overlap between kin selection and sexual selection, particularly concerning how kin selection can put the brakes on harmful sexual conflict. However, there remains a significant disconnect between theory and empirical research. Whilst empirical work has focused on kin-discriminating behaviour, theoretical models have assumed indiscriminating behaviour. Additionally, theoretical work makes particular demographic assumptions that constrain the relationship between genetic relatedness and the scale of competition, and it is not clear that these assumptions reflect the natural setting in which sexual conflict has been empirically studied. Here, we plug this gap between current theoretical and empirical understanding by developing a mathematical model of sexual conflict that incorporates kin discrimination and different patterns of dispersal. We find that kin discrimination and group dispersal inhibit harmful male behaviours at an individual level, but kin discrimination intensifies sexual conflict at the population level.


Behçet's syndrome: clinical presentation and prevalence in Switzerland.
Behçet's syndrome is a rare systemic autoimmune/autoinflammatory disease affecting mucocutaneous tissues, the skin and the eyes, as well as the joints, the central nervous system, the gastrointestinal tract and blood vessels. Because of the lack of clinical data in Switzerland, the aims of this cohort study were to calculate the disease prevalence and to analyse the disease manifestations and the immune-suppressive medication. Data were extracted from 52 patient charts. Thereafter, all patients were interviewed with a questionnaire and 46 had an additional physical examination and laboratory analyses. For calculation of prevalence, data of the national statistical bureau were used. A disease prevalence of 4.03/100,000 inhabitants was calculated. The mean delay between first disease manifestation and diagnosis was 8 years. It was 2 years longer for Swiss than for non-Swiss individuals (p = 0.45). The time intervals between diagnosis and occurrence of different organ manifestations ranged from +8 to -11 years. There was no difference in organ involvement between different ethnicities. Colchicine was prescribed for 52% of patients only, whereas tumour necrosis factor (TNF) inhibitors and glucocorticoids were most frequently prescribed (80 and 64%, respectively). In almost half of the patients, TNF blockers could be stopped and replaced by conventional immunosuppressive drugs. The data from this cohort of Behçet's syndrome patients, the largest in Switzerland, documents a prevalence higher than anticipated. The diagnostic delay underlines an urgent need to improve awareness of the disease and allow timely treatment.


Antibiotic therapy versus no antibiotic therapy for children aged 2 to 59 months with WHO-defined non-severe pneumonia and wheeze.
Worldwide, pneumonia is the leading cause of death amongst children under five years of age, and accounts for approximately two million deaths annually. Pneumonia can be classified according to the World Health Organization (WHO) guidelines. Classification includes assessment of certain clinical signs and symptoms, and the severity of the disease. Treatment is then tailored according to the classification. For non-severe pneumonia, the WHO recommends treatment with oral antibiotics. We used the 2014 WHO definition of non-severe pneumonia for this review: an acute episode of cough, or difficulty in breathing, combined with fast breathing and chest indrawing. The WHO recommends treating non-severe pneumonia with oral antibiotics. Pneumonia is more commonly caused by viruses that do not require antibiotic treatment, but pneumonia caused by bacteria needs management with antibiotics to avoid complications. There is no clear way to quickly distinguish between viral and bacterial pneumonia. It is considered safe to give antibiotics, however, this may lead to the development of antibiotic resistance, and thus, limit their use in future infections. Therefore, it is essential to explore the efficacy of antibiotics for children with WHO-defined non-severe pneumonia and wheeze. To evaluate the efficacy of antibiotic therapy versus no antibiotic therapy for children aged 2 to 59 months with WHO-defined non-severe pneumonia and wheeze. We searched CENTRAL, MEDLINE, Embase, four other databases, and two trial registers (December 2020). We included randomised controlled trials (RCTs) evaluating the efficacy of antibiotic therapy versus no antibiotic therapy for children, aged 2 to 59 months, with non-severe pneumonia and wheeze. We defined non-severe pneumonia as 'a cough or difficulty in breathing, with rapid breathing (a respiratory rate of 50 breaths per minute or more for children aged 2 to 12 months, or a respiratory rate of 40 breaths per minute or more for children aged 12 to 59 months), chest indrawing and wheeze'. We excluded trials involving children with severe or very severe pneumonia, and non-RCTs. Our primary outcomes were clinical cure and treatment failure; secondary outcomes were relapse, mortality, and treatment harms. We used standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of the evidence. Two review authors independently assessed the search results, extracted data, assessed risk of bias and the certainty of the evidence. We contacted the authors of two included trials and the author of the trial awaiting classification to obtain missing numerical outcome data. We included three trials involving 3256 children aged between 2 to 59 months, who exhibited features of non-severe pneumonia with wheeze. The included trials were multi-centre, double-blind, randomised, placebo-controlled trials carried out in Malawi, Pakistan, and India. The children were treated with a three-day course of amoxicillin or placebo, and were followed up for a total of two weeks. We assessed the included trials at overall low risk of bias for random sequence generation, allocation concealment, blinding, attrition bias, and selective reporting. Only one trial was assessed to be at high risk for blinding of outcome assessors. One trial is awaiting classification Antibiotic therapy may result in a reduction of treatment failure by 20% (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.68 to 0.94; three trials; 3222 participants; low-certainty evidence). Antibiotic therapy probably results in little or no difference to clinical cure (RR 1.02, 95% CI 0.96 to 1.08; one trial; 456 participants; moderate-certainty evidence), and in little or no difference to relapse (RR 1.00, 95% CI 0.74 to 1.34; three trials; 2795 participants; low-certainty evidence), and treatment harms (RR 0.81, 95% CI 0.60 to 1.09; three trials, 3253 participants; low-certainty evidence). Two trials (2112 participants ) reported on mortality; no deaths occurred in either group. One trial reported cases of hospitalisation, diarrhoea (with and without dehydration), rash (without itch), tremors, mild nausea and vomiting. We do not currently have enough evidence to support or challenge the continued use of antibiotics for the treatment of non-severe pneumonia. There is a clear need for RCTs to address this question in children aged 2 to 59 months with 2014 WHO-defined non-severe pneumonia and wheeze.


Novel epigallocatechin-3-gallate (EGCG) derivative as a new therapeutic strategy for reducing neuropathic pain after chronic constriction nerve injury in mice.
Neuropathic pain is common in peripheral nerve injury and often fails to respond to ordinary medication. Here, we investigated whether the two novel epigallocatechin-3-gallate (EGCG) polyphenolic derivatives, compound 23 and 30, reduce the neuropathic pain in mice chronic constriction nerve injury (CCI). First, we performed a dose-response study to evaluate nociceptive sensation after administration of EGCG and its derivatives 23 and 30, using the Hargreaves test at 7 and 21 days after injury (dpi). We daily administered EGCG, 23 and 30 (10 to 100 mg/Kg; i.p.) during the first week post-CCI. None of the doses of compound 23 caused significant pain diminution, whereas 50mg/kg was optimal for both EGCG and 30 to delay the latency of paw withdrawal. With 50 mg/Kg, we showed that EGCC prevented the thermal hyperalgesia from 7 to 21 dpi and compound 30 from 14 to 56 dpi. To evaluate the molecular mechanisms underpinning why EGCG and compound 30 differentially prevented the thermal hyperalgesia, we studied several biochemical parameters in the dorsal horn of the spinal cord at 14 and 56 dpi. We showed that the effect observed with EGCG and compound 30 was related to the inhibition of fatty acid synthase (FASN), a known target of these polyphenolic compounds. Additionally, we observed that EGCG and compound 30 reduced the expression of CCI-mediated inflammatory proteins and the nuclear localization of nuclear factor-kappa B at 14 dpi, but not at 56 dpi. We also strongly detected a decrease of synaptic plasma membrane levels of N-methyl-D-asparte receptor 2B in CCI-mice treated with compound 30 at 56 dpi. Altogether, compound 30 reduced the chronic thermal hyperalgesia induced by CCI better than the natural compound EGCG. Thus, our findings provide a rationale for the preclinical development of compound 30 as an agent to treat neuropathic pain.


Cognition, action, and object manipulation.
Although psychology is the science of mental life and behavior, little attention has been paid to the means by which mental life is translated into behavior. One domain in which links between cognition and action have been explored is the manipulation of objects. This article reviews psychological research on this topic, with special emphasis on the tendency to grasp objects differently depending on what one plans to do with the objects. Such differential grasping has been demonstrated in a wide range of object manipulation tasks, including grasping an object in a way that reveals anticipation of the object's future orientation, height, and required placement precision. Differential grasping has also been demonstrated in a wide range of behaviors, including 1-hand grasps, 2-hand grasps, walking, and transferring objects from place to place as well as from person to person. The populations in which the tendency has been shown are also diverse, including nonhuman primates as well as human adults, children, and babies. The tendency is compromised in a variety of clinical populations and in children of a surprisingly advanced age. Verbal working memory is compromised as well if words are memorized while object manipulation tasks are performed; the recency portion of the serial position curve is reduced in this circumstance. In general, the research reviewed here points to rich connections between cognition and action as revealed through the study of object manipulation. Other implications concern affordances, Donders' law, naturalistic observation, and the teaching of psychology.


Cell cycle-regulated binding of c-Abl tyrosine kinase to DNA.
The proto-oncogene c-abl encodes a protein tyrosine kinase that is localized in the cytoplasm and the nucleus. The large carboxyl-terminal segment of c-Abl was found to contain a DNA-binding domain that was necessary for the association of c-Abl with chromatin. The DNA-binding activity of c-Abl was lost during mitosis when the carboxyl-terminal segment became phosphorylated. In vitro phosphorylation of the DNA-binding domain by cdc2 kinase abolished DNA binding. Homozygous mutant mice expressing a c-Abl tyrosine kinase without the DNA-binding domain have been reported to die of multiple defects at birth. Thus, binding of the c-Abl tyrosine kinase to DNA may be essential to its biological function.


Proximal C-terminal domain of sulphonylurea receptor 2A interacts with pore-forming Kir6 subunits in KATP channels.
Functional KATP (ATP-sensitive potassium) channels are hetero-octamers of four Kir6 (inwardly rectifying potassium) channel subunits and four SUR (sulphonylurea receptor) subunits. Possible interactions between the C-terminal domain of SUR2A and Kir6.2 were investigated by co-immunoprecipitation of rat SUR2A C-terminal fragments with full-length Kir6.2 and by analysis of cloned KATP channel function and distribution in HEK-293 cells (human embryonic kidney 293 cells) in the presence of competing rSUR2A fragments. Three maltose-binding protein-SUR2A fusions, rSUR2A-CTA (rSUR2A residues 1254-1545), rSUR2A-CTB (residues 1254-1403) and rSUR2A-CTC (residues 1294-1403), were co-immunoprecipitated with full-length Kir6.2 using a polyclonal anti-Kir6.2 antiserum. A fourth C-terminal domain fragment, rSUR2A-CTD (residues 1358-1545) did not co-immunoprecipitate with Kir6.2 under the same conditions, indicating a direct interaction between Kir6.2 and a 65-amino-acid section of the cytoplasmic C-terminal region of rSUR2A between residues 1294 and 1358. ATP- and glibenclamide-sensitive K+ currents were decreased in HEK-293 cells expressing full-length Kir6 and SUR2 subunits that were transiently transfected with fragments rSUR2A-CTA, rSUR2A-CTC and rSUR2A-CTE (residues 1294-1359) compared with fragment rSUR2A-CTD or mock-transfected cells, suggesting either channel inhibition or a reduction in the number of functional KATP channels at the cell surface. Anti-KATP channel subunit-associated fluorescence in the cell membrane was substantially lower and intracellular fluorescence increased in rSUR2A-CTE expressing cells; thus, SUR2A fragments containing residues 1294-1358 reduce current by decreasing the number of channel subunits in the cell membrane. These results identify a site in the C-terminal domain of rSUR2A, between residues 1294 and 1358, whose direct interaction with full-length Kir6.2 is crucial for the assembly of functional KATP channels.


Polymorphism in tumor necrosis factor genes associated with mucocutaneous leishmaniasis.
Recent studies have shown that mucocutaneous leishmaniasis (MCL), a severe and debilitating form of American cutaneous leishmaniasis (ACL) caused by Leishmania braziliensis infection, is accompanied by high circulating levels of tumor necrosis factor (TNF)-alpha. Analysis of TNF polymorphisms in Venezuelan ACL patients and endemic unaffected controls demonstrates a high relative risk (RR) of 7.5 (P < 0.001) of MCL disease in homozygotes for allele 2 of a polymorphism in intron 2 of the TNF-beta gene, especially in females (RR = 9.5; P < 0.001) compared with males (RR = 4; P < 0.05). A significantly higher frequency (P < 0.05) of allele 2 at the -308-basepair TNF-alpha gene polymorphism was also observed in MCL patients (0.18) compared with endemic control subjects (0.069), again associated with a high relative risk of disease (RR = 3.5; P < 0.05) even in the heterozygous condition. Because both the TNF-alpha and TNF-beta polymorphisms have previously been linked with functional differences in TNF-alpha levels, these data suggest that susceptibility to the mucocutaneous form of disease may be directly associated with regulatory polymorphisms affecting TNF-alpha production.


Rapid analysis of amphetamine, methamphetamine, MDA, and MDMA in urine using solid-phase microextraction, direct on-fiber derivatization, and analysis by GC-MS.
A rapid, sensitive, and solvent-free procedure for the simultaneous determination of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxymethamphetamine (MDMA) in urine was developed using solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) in the selected ion monitoring mode. A headspace vial containing the urine sample, NaOH, NaCl, and amphetamine-d3 as the internal standard was heated at 100 degrees C for 20 min. A polydimethylsiloxane fiber was maintained in the vial headspace for 10 min in order to adsorb the amphetaminic compounds, which were subsequently derivatized by exposing the fiber to trifluoroacetic anhydride for 20 min in the headspace of another vial maintained at 60 degrees C for 20 min. The trifluoroacetyl derivatives were desorbed in the GC injection port for 5 min. Several parameters were considered during the method optimization process. These included a comparison of SPME with or without headspace, the required derivatization procedure, and the influence of temperature on the headspace extraction and derivatization methods. The optimized method was validated for the four compounds tested. Calibration curves showed linearity in the range 50-1000 ng/mL (r = 0.9946-0.9999). Recovery data were 71.89-103.24%. The quantitation limits were 10 ng/mL for amphetamine and methamphetamine and 20 ng/mL for MDA and MDMA. All of these data recommend the applicability of the method for use in the analytical routine of a forensic laboratory.


Ufm1-Specific Ligase Ufl1 Regulates Endoplasmic Reticulum Homeostasis and Protects Against Heart Failure.
Defects in protein homeostasis are sufficient to provoke cardiac remodeling and dysfunction. Although posttranslational modifications by ubiquitin and ubiquitin-like proteins are emerging as an important regulatory mechanism of protein function, the role of Ufm1 (ubiquitin-fold modifier 1)-a novel ubiquitin-like protein-has not been explored in either the normal or stressed heart. Western blotting revealed that Ufl1 (Ufm1-specific E3 ligase 1)-an enzyme essential for Ufm1 modification-was increased in hypertrophic mouse hearts but reduced in the failing hearts of patients with dilated cardiomyopathy. To determine the functional role of Ufl1 in the heart, we generated a cardiac-specific knockout mouse and showed that Ufl1-deficient mice developed age-dependent cardiomyopathy and heart failure, as indicated by elevated cardiac fetal gene expression, increased fibrosis, and impaired cardiac contractility. When challenged with pressure overload, Ufl1-deficient hearts exhibited remarkably greater hypertrophy, exacerbated fibrosis, and worsened cardiac contractility compared with control counterparts. Transcriptome analysis identified that genes associated with the endoplasmic reticulum (ER) function were dysregulated in Ufl1-deficient hearts. Biochemical analysis revealed that excessive ER stress preceded and deteriorated along with the development of cardiomyopathy in Ufl1-deficient hearts. Mechanistically, Ufl1 depletion impaired (PKR-like ER-resident kinase) signaling and aggravated cardiomyocyte cell death after ER stress. Administration of the chemical ER chaperone tauroursodeoxycholic acid to Ufl1-deficient mice alleviated ER stress and attenuated pressure overload-induced cardiac dysfunction. Our results advance a novel concept that the Ufm1 system is essential for cardiac homeostasis through regulation of ER function and that upregulation of myocardial Ufl1 could be protective against heart failure.


Unusual Axillary Artery Branching Pattern Associated with Multiple Neural Variations.
This report presents a unilateral branching pattern of the axillary artery (AA) represented by an unusual common trunk division, vessel multiplications and concomitant neural variations. In a Greek male cadaver, the right AA branched into a subscapular trunk and two accessory lateral thoracic arteries of variable origin and course. Concomitantly, a high-level interconnection between the musculocutaneous and median nerves was identified, as an accessory lateral root of the median nerve. More interestingly, a rare innervation of the upper part of the latissimus dorsi muscle by a lower subscapular nerve was also revealed. In-depth knowledge of the typical and variant AA branching patterns and coexisting neural variations is of paramount importance for surgeons and interventional physicians, for a safer diagnosis and for performing uneventful procedures in that area.


A dynamic transmission model for predicting trends in Helicobacter pylori and associated diseases in the United States.
To assess the benefits of intervention programs against Helicobacter pylori infection, we estimated the baseline curves of its incidence and prevalence. We developed a mathematical (compartmental) model of the intrinsic dynamics of H. pylori, which represents the natural history of infection and disease progression. Our model divided the population according to age, infection status, and clinical state. Case-patients were followed from birth to death. A proportion of the population acquired H. pylori infection and became ill with gastritis, duodenal ulcer, chronic atrophic gastritis, or gastric cancer. We simulated the change in transmissibility consistent with the incidence of gastric cancer and duodenal ulcer over time, as well as current H. pylori prevalence. In the United States, transmissibility of H. pylori has decreased to values so low that, should this trend continue, the organism will disappear from the population without targeted intervention; this process, however, will take more than a century.


Lending a Helping Hand at Work: A Multilevel Investigation of Prosocial Motivation, Inclusive Climate and Inclusive Behavior.
Purpose People with disabilities often encounter difficulties at the workplace such as exclusion or unfair treatment. Researchers have therefore pointed to the need to focus on behavior that fosters inclusion as well as variables that are antecedents of such 'inclusive behavior'. Therefore the purpose of this study was to research the relationship between prosocial motivation, team inclusive climate and employee inclusive behavior. Method A survey was conducted among a sample of 282 paired employees and colleagues, which were nested in 84 teams. Employees self-rated prosocial motivation and team inclusive climate, their inclusive behavior was assessed by colleagues. Hypotheses were tested using multilevel random coefficient modeling. Results Employees who are prosocially motivated will display more inclusive behavior towards people with disabilities, and this relationship is moderated by team inclusive climate in such a way that the relationship is stronger when the inclusive climate is high. Conclusion This study shows that inclusive organizations, which value a diverse workforce, need to be aware of not only individual employee characteristics, but also team level climate to ensure the smooth integrations of people with disabilities into regular work teams.


D-amino acid oxidase generates agonists of the aryl hydrocarbon receptor from D-tryptophan.
The aryl hydrocarbon receptor (AHR) is well-known for its role in mediating the toxic and adaptive responses to xenobiotic compounds. Recent studies also indicate that AHR ligands are endogenously produced and may be essential for normal development. Previously, we showed that the endogenous enzyme, aspartate aminotransferase (AST), generates the AHR proagonist, indole-3-pyruvic acid (I3P), by deamination of its substrate L-tryptophan. We hypothesized that other enzymatic pathways capable of producing I3P may generate AHR agonists in vivo. We now demonstrate that the enzyme d-amino acid oxidase (DAAO) catalyzes the production of AHR agonists through the enzymatic conversion of D-tryptophan to I3P. Moreover, we provide evidence that the nonenzymatic oxidation and condensation of I3P is a critical step in the generation of receptor agonists by DAAO and AST. Products of this process include two novel agonists, 1,3-di(1H-indol-3-yl)propan-2-one and 1-(1H-indol-3-yl)-3-(3H-indol-3-ylidene) propan-2-one [characterized in the accompanying paper, Chowdhury et al. ( 2009 ) Chem. Res. Toxicol. , DOI: 10.1021/tx9000418 ], both of which can potently activate the AHR at concentrations in the nanomolar range. These results show that endogenous AHR activity can be modulated by I3P production from amino acid precursors through multiple enzymatic pathways, including those catalyzed by DAAO and AST.


Newham's Every Child a Sports Person (NECaSP): A Summative Process Evaluation of a School- and Community- Based Intervention in East London, United Kingdom.
The Newman's Every Child a Sports Person (NECaSP) intervention aspires to increase sport and physical activity (PA) participation among young people in the United Kingdom. The aims of this article are to report on a summative process evaluation of the NECaSP and make recommendations for future interventions. Seventeen schools provided data from students aged 11 to 13 years (n = 1226), parents (n = 192), and teachers (n = 14) via direct observation and questionnaires. Means, SDs, and percentages were calculated for sociodemographic data. Qualitative data were analyzed via directed content analysis and main themes identified. Findings indicate further administrative, educational, and financial support will help facilitate the success of the program in improving PA outcomes for young people and of other similar intervention programs globally. Data highlighted the need to engage parents to increase the likelihood of intervention success. One main strength of this study is the mixed-methods nature of the process evaluation. It is recommended that future school-based interventions that bridge sports clubs and formal curriculum provision should consider a broader approach to the delivery of programs throughout the academic year, school week, and school day. Finally, changes in the school curriculum can be successful once all parties are involved (community, school, families).


Development of an online supportive treatment module for moral injury in military veterans and police officers.
Military members and police officers often operate in high stakes situations and under high levels of physical and psychological stress. Consequently, they may be confronted with morally injurious experiences and develop moral injury. Most treatments for moral injury are cognitive-behavioral, face-to-face treatments, which may be supported by online interventions. Online interventions have shown promise in the treatment of trauma-related psychopathology, but few such interventions for moral injury yet exist. To develop and conduct a preliminary evaluation of an online treatment module for moral injury in treatment-seeking military veterans and police officers, to be used in conjunction with regular face-to-face treatment. An online module was developed based on the moral injury literature, using elements from seven existing treatments. A preliminary evaluation was conducted using both quantitative and qualitative methods, and focusing on perceived feasibility, acceptability and engagement of the module, as well as potential benefits and harms. The concept module was evaluated by 15 assessors, including patient representatives, multidisciplinary caregivers and experts. The module was rated favorably, with mean evaluation scores ranging from 7.9 to 8.8 on a 10-point scale. Several suggestions for improvement were made, especially concerning privacy issues, safety instructions, patient-therapist collaborations, and role plays, and the module was adapted accordingly. Using input from literature, patient representatives and experts, we developed an online treatment module for moral injury in military veterans and police officers, to be used in conjunction with face-to-face therapy. Acceptability and feasibility will be further examined in a future pilot study.


Surface and Bulk Effects in Photochemical Reactions and Photomechanical Effects in Dynamic Molecular Crystals.
The increasing number of reports on photomechanical effects in molecular crystals necessitates systematic studies to understand the intrinsic and external effectors that determine and have predictive power of their type and magnitude. Differential light absorption and product gradient between the surface and the bulk of the crystal are often invoked to qualitatively explain the mechanical response of crystals to light; however, the details on how this difference in photochemical response accounts for macroscopic effects such as surface modification, deformation, or disintegration of crystals are yet to be established. Using both bulk- and surface-sensitive analytical techniques, a rare instance of benzylidenefuranone crystals is studied here, and it is capable of several distinct types of photomechanical response including surface striation and delamination, photosalient effect (ballistic disintegration and motion), and photoinduced bending by dimerization. The results provide a holistic view on these effects and set the stage for the development of overarching theoretical models to describe the photomechanics in the ordered solid state.


Influences in fertility decisions among HIV-infected individuals in Lilongwe, Malawi: a qualitative study.
The motivation to have a child may be complex with numerous influencing factors, particularly among individuals living with HIV. This study sought to understand factors influencing fertility decision-making for HIV-infected men and women in Lilongwe, Malawi. Thirteen focus groups were conducted among HIV-infected individuals enrolled in antiretroviral treatment services. Participants identified a hierarchy of influences in fertility decisions including the importance of childbearing, patriarchal influence, family influences and concern regarding HIV transmission. Addressing fertility conversations beyond the confines of a relationship may be important, as family plays a significant role in fertility choices. Childbearing remains a fundamental desire among many individuals with HIV; however, concerns regarding transmission risk need to be addressed with efforts made to overcome misconception and assist individuals in balancing what may be competing influences.


In vitro hydrodynamic characteristics among three bileaflet valves in the mitral position.
The non-fully open phenomenon of the advancing standard medical bileaflet heart valves (the ATS valve) are frequently observed in clinical cases, even though there is no problem with their hemodynamic function. The movement of the leaflets was affected easily by the transvalvular flow because of the unique open pivot design of the ATS valve. In this paper, a comparative in vitro hydrodynamic test was conducted among 3 different types of bileaflet valves, and the effect of different shapes of downstream conduits, which induce different transvalvular flow, on hydrodynamic performance was studied. Three bileaflet valves, the ATS valve, CarboMedics valve (CM), and St. Jude Medical valve (SJM), with an annulus diameter of 29 mm for the mitral position were chosen throughout our experiments. First, pressure drops across the valves under steady flow were measured. Then, the valves were tested at the mitral position with our pneumatically driven pulsatile pump. In this pulsatile flow study, 2 different conduits (straight shape and abrupt enlargement shape) were in turn incorporated at the downstream portion of the mitral valve. A high-speed video camera was employed to observe leaflet movements. In a steady-flow test, the ATS and the SJM produced the same pressure drop, but the CM recorded a higher value. In the pulsatile study, it was observed that the ATS leaflets did not open fully in the mitral position when the downstream conduit with an abrupt enlargement shape was incorporated. However, the CM and the SJM always indicated a fully open movement regardless of the shape of downstream conduits. When the straight downstream conduit was incorporated, the ATS produced a similar pressure drop to that of the SJM, which coincided with the steady test results. When the enlargement conduit was incorporated, however, the ATS presented the lowest pressure drop despite the non-fully open movement. The conduit shape at the valve downstream had a significant influence on the closing volume. These findings indicate that the conduit shape at the valve outlet can affect the hydrodynamic characteristics of bileaflet valves.


Oxidative Stress and Arterial Dysfunction in Peripheral Artery Disease.
Peripheral artery disease (PAD) is an atherosclerotic disease characterized by a narrowing of the arteries in the lower extremities. Disease manifestations are the result of more than just reduced blood flow, and include endothelial dysfunction, arterial stiffness, and inflammation. Growing evidence suggests that these factors lead to functional impairment and decline in PAD patients. Oxidative stress also plays an important role in the disease, and a growing amount of data suggest a link between arterial dysfunction and oxidative stress. In this review, we present the current evidence for the involvement of endothelial dysfunction, arterial stiffness, and inflammation in the pathophysiology of PAD. We also discuss the links between these factors and oxidative stress, with a focus on nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2)-derived reactive oxygen species (ROS) and decreased nitric oxide (NO) bioavailability. Finally, the potential therapeutic role of NOX2 antioxidants for improving arterial function and functional status in PAD patients is explored.


Complete genome sequence of the hyperthermophilic archaeon Thermococcus kodakaraensis KOD1 and comparison with Pyrococcus genomes.
The genus Thermococcus, comprised of sulfur-reducing hyperthermophilic archaea, belongs to the order Thermococcales in Euryarchaeota along with the closely related genus Pyrococcus. The members of Thermococcus are ubiquitously present in natural high-temperature environments, and are therefore considered to play a major role in the ecology and metabolic activity of microbial consortia within hot-water ecosystems. To obtain insight into this important genus, we have determined and annotated the complete 2,088,737-base genome of Thermococcus kodakaraensis strain KOD1, followed by a comparison with the three complete genomes of Pyrococcus spp. A total of 2306 coding DNA sequences (CDSs) have been identified, among which half (1165 CDSs) are annotatable, whereas the functions of 41% (936 CDSs) cannot be predicted from the primary structures. The genome contains seven genes for probable transposases and four virus-related regions. Several proteins within these genetic elements show high similarities to those in Pyrococcus spp., implying the natural occurrence of horizontal gene transfer of such mobile elements among the order Thermococcales. Comparative genomics clarified that 1204 proteins, including those for information processing and basic metabolisms, are shared among T. kodakaraensis and the three Pyrococcus spp. On the other hand, among the set of 689 proteins unique to T. kodakaraensis, there are several intriguing proteins that might be responsible for the specific trait of the genus Thermococcus, such as proteins involved in additional pyruvate oxidation, nucleotide metabolisms, unique or additional metal ion transporters, improved stress response system, and a distinct restriction system.


Serum biomarkers in patients with relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss).
Previous studies suggest a role for eotaxin-3, TARC/CCL17 and IgG4 in newly-diagnosed patients with eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss) with highly active disease. The role of these biomarkers in relapsing disease is unclear. Serum levels of TARC/CCL17, eotaxin-3, IgG4, and IgG4/IgG ratio were determined in serum samples from a longitudinal cohort of patients with EGPA (105 visits of 25 patients). Epidemiological, clinical and laboratory data were available for all visits. At the first visit, 80% of patients were using glucocorticoids and 68% additional immunosuppressive drugs. Disease flares were seen at 18 visits. The median BVAS and BVAS/WG scores at time of relapse were 4 and 2, respectively. None of the biomarkers tested were useful to discriminate between active disease and remission. Patients treated with prednisone had lower eotaxin-3 and eosinophil levels compared to patients not taking glucocorticoids irrespective of disease activity. Use of immunosuppressive agents was not associated with biomarker levels. Serum levels of TARC/CCL17, eotaxin-3, IgG4, and IgG4/IgG ratio do not clearly differentiate active and inactive disease in established EGPA. Defining biomarkers in EGPA remains a challenge especially during times of glucocorticoid use.


Rehabilitation or compensation: time for a fresh perspective on speech and language therapy for dysphagia and Parkinson's disease?
Dysphagia is a common symptom of Parkinson's disease and can have negative consequences for physical health and quality of life. A variety of treatment options are available to clinicians working with people who have dysphagia and Parkinson's disease. These options can be broadly categorized as being compensatory or rehabilitative in nature. To explore the evidence behind treatment options available to clinicians working with dysphagia and Parkinson's disease and to draw conclusions about whether compensatory or rehabilitative approaches are likely to provide the best outcomes for our patients. A critical literature review of compensatory and rehabilitative interventions for dysphagia in Parkinson's disease was undertaken. Relevant studies were analysed for their robustness and potential clinical applications. General conclusions were drawn based on the evidence base identified in this review. This review outlines the lack of evidence supporting both compensatory and rehabilitative methods of treating dysphagia in Parkinson's disease. It directs clinicians and researchers towards areas that require further investigation. To date, compensatory methods of treating dysphagia in Parkinson's disease have received more research attention than rehabilitative methods and yet neither approach has a strong evidence base. This review argues that rehabilitative methods could possibly have greater potential to increase swallowing safety and improve quality of life in the long-term than compensatory methods alone. However, at present there is a lack of research in this area.


An internal promoter underlies the difference in disease severity between N- and C-terminal truncation mutations of Titin in zebrafish.
Truncating mutations in the giant sarcomeric protein Titin result in dilated cardiomyopathy and skeletal myopathy. The most severely affected dilated cardiomyopathy patients harbor Titin truncations in the C-terminal two-thirds of the protein, suggesting that mutation position might influence disease mechanism. Using CRISPR/Cas9 technology, we generated six zebrafish lines with Titin truncations in the N-terminal and C-terminal regions. Although all exons were constitutive, C-terminal mutations caused severe myopathy whereas N-terminal mutations demonstrated mild phenotypes. Surprisingly, neither mutation type acted as a dominant negative. Instead, we found a conserved internal promoter at the precise position where divergence in disease severity occurs, with the resulting protein product partially rescuing N-terminal truncations. In addition to its clinical implications, our work may shed light on a long-standing mystery regarding the architecture of the sarcomere.


An algorithm to assess the need for clinical Monte Carlo dose calculation for small proton therapy fields based on quantification of tissue heterogeneity.
In proton therapy, complex density heterogeneities within the beam path constitute a challenge to dose calculation algorithms. This might question the reliability of dose distributions predicted by treatment planning systems based on analytical dose calculation. For cases in which substantial dose errors are expected, resorting to Monte Carlo dose calculations might be essential to ensure a successful treatment outcome and therefore the benefit is worth a presumably long computation time. The aim of this study was to define an indicator for the accuracy of dose delivery based on analytical dose calculations in treatment planning systems for small proton therapy fields to identify those patients for which Monte Carlo dose calculation is warranted. Fourteen patients treated at our facility with small passively scattered proton beams (apertures diameters below 7 cm) were selected. Plans were generated in the XiO treatment planning system in combination with a pencil beam algorithm developed at the Massachusetts General Hospital and compared to Monte Carlo dose calculations. Differences in the dose to the 50% of the gross tumor volume (D50, GTV) were assessed in a field-by-field basis. A simple and fast methodology was developed to quantify the inhomogeneity of the tissue traversed by a single small proton beam using a heterogeneity index (HI)-a concept presented by Plugfelder et al. [Med. Phys. 34, 1506-1513 (2007)] for scanned proton beams. Finally, the potential correlation between the error made by the pencil beam based treatment planning algorithm for each field and the level of tissue heterogeneity traversed by the proton beam given by the HI was evaluated. Discrepancies up to 5.4% were found in D50 for single fields, although dose differences were within clinical tolerance levels (<3%) when combining all of the fields involved in the treatment. The discrepancies found for each field exhibited a strong correlation to their associated HI-values (Spearman's ρ=0.8, p<0.0001); the higher the level of tissue inhomogeneities for a particular field, the larger the error by the analytical algorithm. With the established correlation a threshold for HI can be set by choosing a tolerance level of 2-3%-commonly accepted in radiotherapy. The HI is a good indicator for the accuracy of proton field delivery in terms of GTV prescription dose coverage when small fields are delivered. Each HI-value was obtained from the CT image in less than 3 min on a computer with 2 GHz CPU allowing implementation of this methodology in clinical routine. For HI-values exceeding the threshold, either a change in beam direction (if feasible) or a recalculation of the dose with Monte Carlo would be highly recommended.


Directed differentiation of embryonic stem cells into bladder tissue.
Manipulatable models of bladder development which interrogate specific pathways are badly needed. Such models will allow a systematic investigation of the multitude of pathologies which result from developmental defects of the urinary bladder. In the present communication, we describe a model in which mouse embryonic stem (ES) cells are directed to differentiate to form bladder tissue by specific interactions with fetal bladder mesenchyme. This model allows us to visualize the various stages in the differentiation of urothelium from ES cells, including the commitment to an endodermal cell lineage, with the temporal profile characterized by examining the induction of specific endodermal transcription factors (Foxa1 and Foxa2). In addition, final functional urothelial differentiation was characterized by examining uroplakin expression. It is well established that ES cells will spontaneously develop teratomas when grown within immunocompromised mouse hosts. We determined the specific mesenchymal to ES cell ratios necessary to dictate organ-specific differentiation while completely suppressing teratomatous growth. Embryonic mesenchyme is well established as an inductive tissue which dictates organ-specific programming of epithelial tissues. The present study demonstrates that embryonic bladder mesenchyme can also steer ES cells towards developing specific endodermal derived urothelium. These approaches allow us to capture specific stages of stem cell differentiation and to better define stem cell hierarchies.


Fano resonances in the nonlinear optical response of coupled plasmonic nanostructures.
The coupling between metallic nanostructures is a common and easy way to control the optical properties of plasmonic systems. Even though the coupling between plasmonic oscillators has been widely studied in the linear regime, its influence on the nonlinear optical response of metallic nanostructures has been sparsely considered. Using a surface integral equation method, we investigate the second order nonlinear optical response of plasmonic metamolecules supporting Fano resonances revealing that the typical lineshape of Fano resonances is also clearly observable in the nonlinear regime. The physical mechanisms leading to nonlinear Fano resonances are revealed by the coupled oscillator model and the symmetry subgroup decomposition. It is found that the origin of the nonlinear scattered wave, i. e. the active plasmonic oscillator, can be selectively chosen. Furthermore, interferences between nonlinear emissions are clearly observed in specific configurations. The results presented in this article pave the way for the design of efficient nonlinear plasmonic metamolecules with controlled nonlinear radiation.


Efficacy of population-wide diabetes and obesity prevention programs: An overview of systematic reviews on proximal, intermediate, and distal outcomes and a meta-analysis of impact on BMI.
We conducted an overview of systematic reviews and a meta-analysis of the impact on body mass index (BMI) of primary studies of population-wide obesity and diabetes prevention programs, in order to evaluate their efficacy. We searched eight databases for reviews of population-level programs reporting effect on diet, physical activity, BMI, or prevalence of obesity/overweight or type 2 diabetes mellitus (T2DM). Meta-analysis of primary studies within reviews reporting effect on BMI. Interventions were categorized using ANGELO framework and quality assessment using AMSTAR. Fifty-three systematic reviews were included. Primary studies were largely natural experiments or cross-sectional studies of national data. Increased price of sugar-sweetened beverages (SSBs) and fast food, decreased price of fruit and vegetables, food labelling, and grocery store interventions were associated with positive effects on diet. Park and playground renovations and point-of-choice prompts to increase stair use were associated with positive effects on physical activity. Increased price of SSBs, menu labelling, grocery store interventions, and multicomponent interventions were associated with small reductions in BMI. There was insufficient evidence of impact of any interventions on the prevalence of overweight, obesity, or T2DM. We have identified a promising suite of population-wide actions to improve diet, increase physical activity, and reduce BMI. Impact on subsequent incidence of T2DM remains speculative.


Branch-point reconstruction in laser beam projection through turbulence with finite-degree-of-freedom phase-only wave-front correction.
Wave-front sensing and deformable mirror control algorithms in adaptive optics systems are designed on the premise that a continuous phase function exists in the telescope pupil that can be conjugated with a deformable mirror for the purpose of projecting a laser beam. However, recent studies of coherent wave propagation through turbulence have shown that under conditions where scintillation is not negligible, a truly continuous phase function does not in general exist as a result of the presence of branch points in the complex optical field. Because of branch points and the associated branch cuts, least-squares wave-front reconstruction paradigms can have large errors. We study the improvement that can be obtained by implementing wave-front reconstructors that can sense the presence of branch points and reconstruct a discontinuous phase function in the context of a laser beam projection system. This study was conducted by fitting a finite-degree-of-freedom deformable mirror to branch-point and least-squares reconstructions of the phase of the beacon field, propagating the corrected field to the beacon plane, and evaluating performance in the beacon plane. We find that the value of implementing branch-point reconstructors with a finite-degree-of-freedom deformable mirror is significant for optical paths that cause saturated log-amplitude fluctuations.


Absolute lymphocyte count as a surrogate marker for CD4 counts after six months of HAART initiation in a resource-limited setting in India.
Owing to the ever-expanding access to HAART (highly active anti-retroviral therapy) in resource-limited settings, there is a need to evaluate alternate markers like absolute lymphocyte count (ALC) as a surrogate for CD4 counts. This study was done to assess the usefulness of ALC as a surrogate marker for CD4 counts in monitoring HIV-infected patients after HAART initiation. In this study, 108 HIV-positive adult patients of both sexes fulfilling the inclusion criteria were included. CD4 and ALC were recorded at baseline. After initiation on HAART, these patients were followed up at three month intervals. ALC and CD4 counts were positively correlated (Spearman correlation coefficient= 0.553). After six months of HAART, the sensitivity of an ALC increase as a marker for CD4 count increase at six months was 82 per cent, specificity was 100 per cent, PPV was 100 per cent and NPV was 31 per cent. Area under the corresponding ROC curve for CD4 increase of >100 cells/μl was 0. 825 ± 0.053. ALC may be a useful surrogate marker in predicting an increase in CD4 counts as a response to HAART, but of questionable value in predicting a decrease in CD4 counts.


Nanostructured TiO2 surfaces promote polarized activation of microglia, but not astrocytes, toward a proinflammatory profile.
Activation of glial cells, including astrocytes and microglia, has been implicated in the inflammatory responses underlying brain injury and neurodegenerative diseases including Alzheimer's and Parkinson's diseases. The classic activation state (M1) is characterized by high capacity to present antigens, high production of nitric oxide (NO) and reactive oxygen species (ROS) and proinflammatory cytokines. Classically activated cells act as potent effectors that drive the inflammatory response and may mediate detrimental effects on neural cells. The second phenotype (M2) is an alternative, apparently beneficial, activation state, more related to a fine tuning of inflammation, scavenging of debris, promotion of angiogenesis, tissue remodeling and repair. Specific environmental chemical signals are able to induce these different polarization states. We provide here evidence that nanostructured substrates are able, exclusively in virtue of their physical properties, to push microglia toward the proinflammatory activation phenotype, with an efficacy which reflects the graded nanoscale rugosity. The acquisition of a proinflammatory phenotype appears specific for microglia and not astrocytes, indicating that these two cell types, although sharing common innate immune responses, respond differently to external physical stimuli.


Specific absorption rate levels measured in a phantom head exposed to radio frequency transmissions from analog hand-held mobile phones.
Electric fields (E-fields) induced within a phantom head from exposure to three different advanced mobile phone system (AMPS) hand-held telephones were measured using an implantable E-field probe. Measurements were taken in the eye nearest the phone and along a lateral scan through the brain from its centre to the side nearest the phone. During measurement, the phones were positioned alongside the phantom head as in typical use and were configured to transmit at maximum power (600 mW nominal). The specific absorption rate (SAR) was calculated from the in situ E-field measurements, which varied significantly between phone models and antenna configuration. The SARs induced in the eye ranged from 0.007 to 0.21 W/kg. Metal-framed spectacles enhanced SAR levels in the eye by 9-29%. In the brain, maximum levels were recorded at the measurement point closest to the phone and ranged from 0.12 to 0.83 W/kg. These SARs are below peak spatial limits recommended in the U.S. and Australian national standards [IEEE Standards Coordinating Committee 28 (1991): C95.1-1991 and Standards Australia (1990): AS2772.1-1990] and the IRPA guidelines for safe exposure to radio frequency (RF) electromagnetic fields [IRPA (1988): Health Phys 54:115-123]. Furthermore, a detailed thermal analysis of the eye indicated only a 0.022 degrees C maximum steady-state temperature rise in the eye from a uniform SAR loading of 0.21 W/kg. A more approximate thermal analysis in the brain also indicated only a small maximum temperature rise of 0.034 degrees C for a local SAR loading of 0.83 W/kg.


Contribution of mutations in gyrA and parC genes to fluoroquinolone resistance of mutants of Streptococcus pneumoniae obtained in vivo and in vitro.
We have analyzed by gene amplification and sequencing mutations in the quinolone resistance-determining regions of the gyrA, gyrB, and parC genes of fluoroquinolone-resistant Streptococcus pneumoniae mutants obtained during therapy or in vitro. Mutations leading to substitutions in ParC were detected in the two mutants obtained in vivo, BM4203-R (substitution of a histidine for an aspartate at position 84 [Asp-84-->His]; Staphylococcus aureus coordinates) and BM4204-R (Ser-80-->Phe), and in two mutants obtained in vitro (Ser-80-->Tyr). An additional mutant obtained in vitro, BM4205-R3, displayed a higher level of fluoroquinolone resistance and had a mutation in gyrA leading to a Ser-84-->Phe change. We could not detect any mutation in the three remaining mutants obtained in vitro. Total DNA from BM4203-R, BM4204-R, and BM4205-R3 was used to transform S. pneumoniae CP1000 by selection on fluoroquinolones. For the parC mutants, transformants with phenotypes indistinguishable from those of the donors were obtained at frequencies (5 x 10(-3) to 8 x 10(-3)) compatible with monogenic transformation. By contrast, transformants were obtained at a low frequency (4 x 10(-5)), compatible with the transformation of two independent genes, for the gyrA mutant. Resistant transformants of CP1000 were also obtained with an amplified fragment of parC from BM4203-R and BM4204-R but not with a gyrA fragment from BM4205-R3. All transformants had mutations identical to those in the donors. These data strongly suggest that ParC is the primary target for fluoroquinolones in S. pneumoniae and that BM4205-R3 is resistant to higher levels of the drugs following the acquisition of two mutations, including one in gyrA.


Effects of dietary sulphur sources on concentrations of hydrogen sulphide in the rumen head-space gas of dairy cows.
Three change-over design experiments investigated the origin of hydrogen sulphide in the rumen head-space gas of dairy cows, comparing the effects of single iso-S additions of methionine, cysteine and sodium sulphate, as well as the effects of single meals of fresh ryegrass or white clover. The concentration of hydrogen sulphide in rumen gas declined close to zero within 4 h after withdrawal of the previous feed. Sulphur sources were then given to cows and concentrations of hydrogen sulphide recorded in rumen head-space gas at 30-min intervals. Cysteine addition (8 g) led to a rapid (within 30 min) and a large (490 and 957 p.p.m. respectively in two experiments) increase in hydrogen sulphide concentration. Concentrations were significantly less following methionine addition. Increasing levels of cysteine addition led to significant increases in hydrogen sulphide concentrations ( P < 0.001 for the linear effect), although peak hydrogen sulphide was delayed and concentrations remained higher for longer with the highest (12 g) addition of cysteine ( P < 0.01 for the 'cysteine level' × 'time' interaction). The increase in concentration of hydrogen sulphide from sodium sulphate was smaller (230 p.p.m.) and slower (2 h) than for cysteine. Despite the much higher intake of cystine for white clover in comparison with perennial ryegrass ( P < 0.001), there was almost no increase in hydrogen sulphide concentration in rumen head-space gas from cows fed white clover. It seems likely that this is associated with the use of sulphur to produce thiocyanate to detoxify the hydrogen cyanide from cyanogenic white clover.


You are how you eat: fast food and impatience.
Based on recent advancements in the behavioral priming literature, three experiments investigated how incidental exposure to fast food can induce impatient behaviors and choices outside of the eating domain. We found that even an unconscious exposure to fast-food symbols can automatically increase participants' reading speed when they are under no time pressure and that thinking about fast food increases preferences for time-saving products while there are potentially many other product dimensions to consider. More strikingly, we found that mere exposure to fast-food symbols reduced people's willingness to save and led them to prefer immediate gain over greater future return, ultimately harming their economic interest. Thus, the way people eat has far-reaching (often unconscious) influences on behaviors and choices unrelated to eating.


Empowering the Internet of Vehicles with Multi-RAT 5G Network Slicing.
Internet of Vehicles (IoV) is a hot research niche exploiting the synergy between Cooperative Intelligent Transportation Systems (C-ITS) and the Internet of Things (IoT), which can greatly benefit of the upcoming development of 5G technologies. The variety of end-devices, applications, and Radio Access Technologies (RATs) in IoV calls for new networking schemes that assure the Quality of Service (QoS) demanded by the users. To this end, network slicing techniques enable traffic differentiation with the aim of ensuring flow isolation, resource assignment, and network scalability. This work fills the gap of 5G network slicing for IoV and validates it in a realistic vehicular scenario. It offers an accurate bandwidth control with a full flow-isolation, which is essential for vehicular critical systems. The development is based on a distributed Multi-Access Edge Computing (MEC) architecture, which provides flexibility for the dynamic placement of the Virtualized Network Functions (VNFs) in charge of managing network traffic. The solution is able to integrate heterogeneous radio technologies such as cellular networks and specific IoT communications with potential in the vehicular sector, creating isolated network slices without risking the Core Network (CN) scalability. The validation results demonstrate the framework capabilities of short and predictable slice-creation time, performance/QoS assurance and service scalability of up to one million connected devices.


Joint learning of gene functions--a Bayesian network model approach.
In this paper, we develop a machine learning system for determining gene functions from heterogeneous data sources using a Weighted Naive Bayesian network (WNB). The knowledge of gene functions is crucial for understanding many fundamental biological mechanisms such as regulatory pathways, cell cycles and diseases. Our major goal is to accurately infer functions of putative genes or Open Reading Frames (ORFs) from existing databases using computational methods. However, this task is intrinsically difficult since the underlying biological processes represent complex interactions of multiple entities. Therefore, many functional links would be missing when only one or two sources of data are used in the prediction. Our hypothesis is that integrating evidence from multiple and complementary sources could significantly improve the prediction accuracy. In this paper, our experimental results not only suggest that the above hypothesis is valid, but also provide guidelines for using the WNB system for data collection, training and predictions. The combined training data sets contain information from gene annotations, gene expressions, clustering outputs, keyword annotations, and sequence homology from public databases. The current system is trained and tested on the genes of budding yeast Saccharomyces cerevisiae. Our WNB model can also be used to analyze the contribution of each source of information toward the prediction performance through the weight training process. The contribution analysis could potentially lead to significant scientific discovery by facilitating the interpretation and understanding of the complex relationships between biological entities.


Polarized transport of the polymeric immunoglobulin receptor in transfected rabbit mammary epithelial cells.
A cDNA for the rabbit low Mr polymeric immunoglobulin (poly-Ig) receptor was expressed in an immortalized rabbit mammary cell line. The intracellular routing of the receptor and its cell surface expression was analyzed in stably transfected cells grown on permeable supports. Initially the cells formed a monolayer with no transmural electrical resistance. All monolayer cells expressed the poly-Ig receptor and cytokeratin 7 filaments characteristic of luminal mammary cells but absent in myoepithelial cells. Within 7 d in culture, the cells underwent cytodifferentiation and formed a bilayer with a transepithelial electrical resistance of approximately 500 omega x cm2. Upper layer cells formed tight junctions with adjacent cells and gap junctions with basal cells. Expression of the poly-Ig receptor and cytokeratin 7 was restricted to the cells from the upper layer. The kinetics of receptor biosynthesis and processing was similar to that reported for rabbit mammary gland and rat liver. The receptor was cleaved at the apical cell surface and release of secretory component into the apical medium occurred with a half-time of approximately 2 h. Selective cell surface trypsinization combined with pulse-chase experiments served to determine at which cell surface domain newly synthesized receptor appeared first. The receptor was digested with a half-time of approximately 60 min with trypsin present in the basolateral medium and 90 min with apical trypsin. These data are consistent with selective targeting of newly synthesized receptor to the basolateral surface. The results indicate that transcytosis of the receptor from basolateral to apical membrane in the presence or the absence of its ligand requires approximately 30 min. Cleavage of the receptor by endogenous protease is not concomitant with its appearance at the apical surface, but requires additional time, thus explaining the presence of intact receptor on the apical membrane.


Absence of the Fragile X messenger ribonucleoprotein alters response patterns to sounds in the auditory midbrain.
Among the different autism spectrum disorders, Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. Sensory and especially auditory hypersensitivity is a key symptom in patients, which is well mimicked in the Fmr1 -/- mouse model. However, the physiological mechanisms underlying FXS's acoustic hypersensitivity in particular remain poorly understood. Here, we categorized spike response patterns to pure tones of different frequencies and intensities from neurons in the inferior colliculus (IC), a central integrator in the ascending auditory pathway. Based on this categorization we analyzed differences in response patterns between IC neurons of wild-type (WT) and Fmr1 -/- mice. Our results report broadening of frequency tuning, an increased firing in response to monaural as well as binaural stimuli, an altered balance of excitation-inhibition, and reduced response latencies, all expected features of acoustic hypersensitivity. Furthermore, we noticed that all neuronal response types in Fmr1 -/- mice displayed enhanced offset-rebound activity outside their excitatory frequency response area. These results provide evidence that the loss of Fmr1 not only increases spike responses in IC neurons similar to auditory brainstem neurons, but also changes response patterns such as offset spiking. One can speculate this to be an underlying aspect of the receptive language problems associated with Fragile X syndrome.


Individualized fracture risk assessment: State-of-the-art and room for improvement.
Fragility fracture is a serious clinical event, because it is associated with increased risk of mortality and reduced quality of life. The risk of fracture is determined by multiple risk factors, and their effects may be interactional. Over the past 10 years, a number of predictive models (e.g., FRAX, Garvan Fracture Risk Calculator, and Qfracture) have been developed for individualized assessment of fracture risk. These models use different risk profiles to estimate the probability of fracture over 5- and 10-year period. The ability of these models to discriminate between those individuals who will and will not have a fracture (i.e., area under the receiver operating characteristic curve [AUC]) is generally acceptable-to-good (AUC, 0.6 to 0.8), and is highly variable between populations. The calibration of existing models is poor, particularly in Asian populations. There is a strong need for the development and validation of new prediction models based on Asian data for Asian populations. We propose approaches to improve the accuracy of existing predictive models by incorporating new markers such as genetic factors, bone turnover markers, trabecular bone score, and time-variant factors. New and more refined models for individualized fracture risk assessment will help identify those most likely to sustain a fracture, those most likely to benefit from treatment, and encouraging them to modify their risk profile to decrease risk.


Reducing risky sexual behavior and substance use among currently and formerly homeless adults living with HIV.
We examined the efficacy of the Healthy Living Program in reducing risky sexual behavior and substance use among adults with HIV infection who were marginally housed (i.e., homeless at some point over a 37-month period). We had previously conducted a randomized controlled trial with 936 adults living with HIV infection. In that study, 3 intervention modules of 5 sessions each addressed different goals: reducing risky sexual acts and drug use, improving the quality of life, and adhering to healthful behaviors. Participants were interviewed at baseline and at 5, 10, 15, 20, and 25 months; 746 completed 4 or more assessments. In this study, we analyzed sexual behavior and drug use outcomes for the 35% (n = 270 of 767) of participants who were considered marginally housed. Among the marginally housed participants, there were significantly greater reductions in unprotected risky sexual acts, the number of sexual partners of HIV negative or unknown serostatus, alcohol or marijuana use, and hard drug use among the intervention group than among the control group. Intensive, skill-focused intervention programs may improve the lives of marginally housed adults living with HIV infection.


Presentation of viral antigen to class I major histocompatibility complex-restricted cytotoxic T lymphocyte. Recognition of an immunodominant influenza hemagglutinin site by cytotoxic T lymphocyte is independent of the position of the site in the hemagglutinin translation product.
Class I major histocompatibility complex (MHC) restricted T lymphocytes preferentially recognize fragments of polypeptides processed through a nonendosomal presentation pathway. At present the intracellular compartment(s) in which polypeptide fragmentation occurs and factors which influence the formation of an antigenic epitope are not well understood. To assess the role of residues flanking an antigenic site in the generation of the antigenic moiety recognized by class I MHC restricted T lymphocytes we have moved the coding sequence for an immunodominant H-2Kd restricted site on the influenza A/JAPAN/57 hemagglutinin (residues 202-221) by site-directed mutagenesis to six different positions along the coding sequence of the hemagglutinin gene. We have found that all six classes of mutants are recognized by MHC class I restricted T cells as efficiently as the wild type hemagglutinin gene product. Thus neither N-terminal to C-terminal position within the translation product nor sequences flanking the antigenic site influence processing.


Social contexts of regular smoking in adolescence: towards a multidimensional ecological model.
Using data from the Add Health, this study examined multilevel factors of adolescent smoking after controlling for the baseline smoking behavior and individual characteristics. Results showed that peer, family and school were all important life domains contextually influencing subsequent smoking behavior among adolescents. Time spent with peers, best friend smoking and household member smoking were associated with higher risk. Parent-child closeness, parental control, attending a private school and having a higher percentage of Hispanic students at school were protective factors. Significant interaction effects were found between parental control and household member smoking and between parent-child closeness and communication. None of the neighborhood- and state-level factors were significant in the final full model but they were significant in reduced models. More proximate social contexts appear to play a more direct and immediate role in adolescent smoking than macro-level factors. An ecological model incorporating multiple social systems seems more fruitful than single-system models to reveal etiology of adolescent smoking.


Elizabethkingia anophelis sp. nov., isolated from the midgut of the mosquito Anopheles gambiae.
The taxonomic position, growth characteristics and antibiotic resistance properties of a slightly yellow-pigmented bacterial strain, designated R26(T), isolated from the midgut of the mosquito Anopheles gambiae, were studied. The isolate produced rod-shaped cells, which stained Gram-negative. The bacterium had two growth optima at 30-31 °C and 37 °C. Strain R26(T) demonstrated natural antibiotic resistance to ampicillin, chloramphenicol, kanamycin, streptomycin and tetracycline. 16S rRNA gene sequence analysis revealed that the isolate showed 98.6 % sequence similarity to that of Elizabethkingia meningoseptica ATCC 13253(T) and 98.2 % similarity to that of Elizabethkingia miricola GTC 862(T). The major fatty acids of strain R26(T) were iso-C(15 : 0), iso-C(17 : 0) 3-OH and summed feature 4 (iso-C(15 : 0) 2-OH and/or C(16 : 1)ω7c/t). Strain R26(T) contained only menaquinone MK-6 and showed a complex polar lipid profile consisting of diphosphatidylglycerol, phosphatidylinositol, an unknown phospholipid and unknown polar lipids and glycolipids. DNA-DNA hybridization experiments with E. meningoseptica CCUG 214(T) ( = ATCC 13253(T)) and E. miricola KCTC 12492(T) ( = GTC 862(T)) gave relatedness values of 34.5 % (reciprocal 41.5 %) and 35.0 % (reciprocal 25.7 %), respectively. DNA-DNA hybridization results and some differentiating biochemical properties indicate that strain R26(T) represents a novel species, for which the name Elizabethkingia anophelis sp. nov. is proposed. The type strain is R26(T) ( = CCUG 60038(T) = CCM 7804(T)).


Diversity of methanogens and sulfate-reducing bacteria in the interfaces of five deep-sea anoxic brines of the Red Sea.
Oceanic deep hypersaline anoxic basins (DHABs) are characterized by drastic changes in physico-chemical conditions in the transition from overlaying seawater to brine body. Brine-seawater interfaces (BSIs) of several DHABs across the Mediterranean Sea have been shown to possess methanogenic and sulfate-reducing activities, yet no systematic studies have been conducted to address the potential functional diversity of methanogenic and sulfate-reducing communities in the Red Sea DHABs. Here, we evaluated the relative abundance of Bacteria and Archaea using quantitative PCR and conducted phylogenetic analyses of nearly full-length 16S rRNA genes as well as functional marker genes encoding the alpha subunits of methyl-coenzyme M reductase (mcrA) and dissimilatory sulfite reductase (dsrA). Bacteria predominated over Archaea in most locations, the majority of which were affiliated with Deltaproteobacteria, while Thaumarchaeota were the most prevalent Archaea in all sampled locations. The upper convective layers of Atlantis II Deep, which bear increasingly harsh environmental conditions, were dominated by members of the class Thermoplasmata (Marine Benthic Group E and Mediterranean Sea Brine Lakes Group 1). Our study revealed unique microbial compositions, the presence of niche-specific groups, and collectively, a higher diversity of sulfate-reducing communities compared to methanogenic communities in all five studied locations.


Biomechanical characteristics of head injuries from falls in children younger than 48 months.
A fall-height threshold is important when evaluating the likelihood of structural head injury or abusive head trauma. This study investigates witnessed falls to correlate the fall characteristics with the extent of injury. Case-control study of children aged ≤48 months who attended one hospital following a fall from <3 m (10 ft), comparing cases who sustained a skull fracture or intracranial injury (ICI) with controls, who had minor head injuries. Characteristics included: the mechanism of injury, surface of impact, site of impact to the head and fall height. Forty-seven children had a skull fracture or ICI, while 416 children had minor head injuries. The mean fall height for minor head injuries was significantly lower than that causing skull fracture/ICI (p<0.001). No skull fracture/ICI was recorded in children who fell <0.6 m (2 ft), based on the height of the head centre of gravity. Skull fractures/ICI were more likely in children aged ≤12 months (p<0.001) from impacts to the temporal/parietal or occipital region (p<0.001), impacts onto wood (p=0.004) and falls from a carer's arms, particularly when on stairs (p<0.001). No significant difference was reported between the mean fall heights of children who had a simple skull fracture (n=17) versus those who had a complex fracture or ICI (n=30). An infant is more likely to sustain a skull fracture/ICI from a fall above a 0.6 m (2 ft) threshold, based on the height of the head centre of gravity, or with a parietal/temporal or occipital impact. These variables should be recorded when evaluating the likelihood of skull fracture/ICI.


Low dialysate potassium concentration: an overrated risk factor for cardiac arrhythmia?
Serum potassium concentrations rise with dietary potassium intake between dialysis sessions and are often at hyperkalemic levels by the next session. Conversely, potassium concentrations fall during each hemodialysis, and sometimes reach hypokalemic levels by the end. Low potassium dialysate, which rapidly decreases serum potassium and often brings it to hypokalemic levels, is almost universally considered a risk factor for life-threatening arrhythmias. While there is little doubt about the threat of lethal arrhythmias due to hyperkalemia, convincing evidence for the danger of low potassium dialysate and rapid or excess potassium removal has not been forthcoming. The original report of more frequent ventricular ectopy in early dialysis that was improved by reducing potassium removal has received very little confirmation from subsequent studies. Furthermore, the occurrence of ventricular ectopy during dialysis does not appear to predict mortality. Studies relating sudden deaths to low potassium dialysate are countered by studies with more thorough adjustment for markers of poor health. Dialysate potassium concentrations affect the excursions of serum potassium levels above or below the normal range, and have the potential to influence dialysis safety. Controlled studies of different dialysate potassium concentration and their effect on mortality and cardiac arrests have not been done. Until these results become available, I propose interim guidelines for the setting of dialysate potassium levels that may better balance risks and benefits.


Oil spills: method for measuring their extent on the sea surface.
It is difficult to estimate the area affected by an oil spill at sea, the degree of coverage by oil pollutants within the affected area, and the quantity of pollutants involved. Estimates of volumes and flow rates are based on estimated changes in areal extent of the spill. Uncertainties in measurement of area degrade the accuracy of estimating other parameters. To resolve this problem, available stock components have now been assembled into a system that yields repeatable, economical measurement of the areal extent of oil spills at acceptable levels of accuracy. The system comprises overflights with a thermal infrared imaging system, densitometric color enhancement of the infrared images, and automatic digital planimetry of the areas of specified image densities.


Complication with intraosseous access: scandinavian users' experience.
Intraosseous access (IO) is indicated if vascular access cannot be quickly established during resuscitation. Complication rates are estimated to be low, based on small patient series, model or cadaver studies, and case reports. However, user experience with IO use in real-life emergency situations might differ from the results in the controlled environment of model studies and small patient series. We performed a survey of IO use in real-life emergency situations to assess users' experiences of complications. An online questionnaire was sent to Scandinavian emergency physicians, anesthesiologists and pediatricians. 1,802 clinical cases of IO use was reported by n=386 responders. Commonly reported complications with establishing IO access were patient discomfort/pain (7.1%), difficulties with penetration of periosteum with IO needle (10.3%), difficulties with aspiration of bone marrow (12.3%), and bended/broken needle (4.0%). When using an established IO access the reported complications were difficulties with injection fluid and drugs after IO insertion (7.4%), slow infusion (despite use of pressure bag) (8.8%), displacement after insertion (8.5%), and extravasation (3.7%). Compartment syndrome and osteomyelitis occurred in 0.6% and 0.4% of cases respectively. In users' recollection of real-life IO use, perceived complications were more frequent than usually reported from model studies. The perceived difficulties with using IO could affect the willingness of medical staff to use IO. Therefore, user experience should be addressed both in education of how to use, and research and development of IOs.


Characterisation of Arctic Bacterial Communities in the Air above Svalbard.
Atmospheric dispersal of bacteria is increasingly acknowledged as an important factor influencing bacterial community biodiversity, biogeography and bacteria-human interactions, including those linked to human health. However, knowledge about patterns in microbial aerobiology is still relatively scarce, and this can be attributed, in part, to a lack of consensus on appropriate sampling and analytical methodology. In this study, three different methods were used to investigate aerial biodiversity over Svalbard: impaction, membrane filtration and drop plates. Sites around Svalbard were selected due to their relatively remote location, low human population, geographical location with respect to air movement and the tradition and history of scientific investigation on the archipelago, ensuring the presence of existing research infrastructure. The aerial bacterial biodiversity found was similar to that described in other aerobiological studies from both polar and non-polar environments, with Proteobacteria, Actinobacteria, and Firmicutes being the predominant groups. Twelve different phyla were detected in the air collected above Svalbard, although the diversity was considerably lower than in urban environments elsewhere. However, only 58 of 196 bacterial genera detected were consistently present, suggesting potentially higher levels of heterogeneity. Viable bacteria were present at all sampling locations, showing that living bacteria are ubiquitous in the air around Svalbard. Sampling location influenced the results obtained, as did sampling method. Specifically, impaction with a Sartorius MD8 produced a significantly higher number of viable colony forming units (CFUs) than drop plates alone.


Center-of-pressure movements during equine-assisted activities.
We compared anteroposterior and mediolateral range of motion and velocity of the center of pressure (COP) on the horse's back between riders without disabilities and riders with cerebral palsy. An electronic pressure mat was used to track COP movements beneath the saddle in 4 riders without disabilities and 4 riders with cerebral palsy. Comparisons between rider groups were made using the Mann-Whitney test (p < .05). The two rider groups differed significantly in anteroposterior range of COP motion, mediolateral range of COP motion, and mediolateral COP velocity. Anteroposterior COP velocity did not differ between groups. The results suggest that measurements of COP range of motion and velocity are potentially useful for monitoring changes in balance as an indicator of core stability during equine-assisted activities.


DNA bacterial load in children with bacteremic pneumococcal community-acquired pneumonia.
This study was conducted to evaluate the association between pneumococcal DNA load and parapneumonic pleural effusion (PPE) in children with community-acquired pneumonia. Bacterial load was quantified and related to the presence of PPE with or without empyema in 72 otherwise healthy children aged ≤5 years who were hospitalised because of radiographically confirmed CAP and showed a real-time polymerase chain reaction that was positive for Streptococcus pneumoniae. The proportion of children with a high bacterial load (i.e. ≥265 DNA copies/mL) was larger among the subjects with PPE than those without it. Multivariate analysis showed that a high bacterial load was significantly associated with PPE (OR 8.65; 95% CI 1.10-67.8 vs a bacterial load of <125 copies/mL). Children with infection due to pneumococcal serotype 19A were at highest risk of developing PPE (OR 7.44; 95% CI 1.10-50.4 vs all other typeable serotypes). The patients with CAP due to pneumococcal serotypes that are not included in the 13-valent conjugate vaccine (PCV13) were more frequently affected by PPE than those with infections associated with serotypes included in the vaccine, except for serotype 19A. Bacterial loads of ≥265 DNA copies/mL are significantly associated with PPE, and serotype 19A is significantly associated with a high bacterial load and the development of PPE. The mean bacterial load of the patients with empyema was higher than that of patients with simple PPE. Although further studies are required, it seems that serotypes not included in PCV13 can play a major role in causing a higher bacterial load and PPE.


Early Years Policy.
In this paper, we analyze the role that early years policy might play in narrowing educational attainment gaps. We begin by examining gaps in school readiness between low-, middle-, and high-income children, drawing on data from new large and nationally representative birth cohort studies in the US and UK. We find that sizable income-related gaps in school readiness are present in both countries before children enter school and then decompose these gaps to identify the factors that account for the poorer scores of low-income children. We then consider what role early years policy could play in tackling these gaps, drawing on the best available evidence to identify promising programs.


A genome-wide survey over the ChIP-on-chip identified androgen receptor-binding genomic regions identifies a novel prostate cancer susceptibility locus at 12q13.13.
The molecular mechanisms for the genome-wide association studies (GWAS)-identified prostate cancer (PCa) risk-associated single-nucleotide polymorphisms (SNP) remain largely unexplained. One recent finding that the PCa risk SNPs are enriched in genomic regions containing androgen receptor (AR)-binding sites has suggested altered AR signaling as a potentially important mechanism. To explore novel associations by leveraging this knowledge, we utilized a meta-analysis previously done over SNPs harbored in ChIP-on-chip identified AR-binding genomic regions using the GWAS data from the Johns Hopkins Hospital (JHH) and the Cancer Genetic Markers of Susceptibility (CGEMS) study, and subsequently evaluated the top associations in a third population from the CAncer of the Prostate in Sweden (CAPS) study. One SNP (rs4919743: G>A), located at the KRT8 locus at 12q13.13 which encodes a keratin protein (K8) long used as a prostate epithelial malignancy marker and implicated in the tumorigenesis of several cancer types, was identified to be associated with PCa risk. The frequency of its minor "A" allele was consistently higher in PCa cases than in controls in all three study populations, with a combined OR of 1.22 (95% CI: 1.13-1.32) and an overall P value of 4.50 × 10(-7) (Bonferroni corrected, P = 0.006). We have identified a novel genetic locus that is associated with PCa risk. This study illustrated the great potential of prior biological knowledge in facilitating the search for novel disease-associated genetic loci. This finding warrants further replication in other studies.


Whistle-blowing and workplace culture in older peoples' care: qualitative insights from the healthcare and social care workforce.
Inquiries in the UK into mistreatment of older people by healthcare employees over the last 30 years have focused on introducing or supporting employee whistle-blowing. Although whistle-blowers have made an important contribution to patient safety it remains a controversial activity. The fate of whistle-blowers is bleak, often resulting in personal and professional sacrifices. Here we draw on the views of healthcare and social care employees working with older people to explore perceptions of whistle-blowing as well as alternative strategies that may be used to raise concerns about the mistreatment of patients by co-workers. Whistle-blowing was perceived as a negative term. Managers said they promoted open cultures underpinned by regular team meetings and an open-door ethos. Others described workplace norms that were somewhat at odds with these open culture ideals. Whistle-blowing was considered risky, and this led to staff creating informal channels through which to raise concerns. Those who witnessed wrongdoing were aware that support was available from external agencies but preferred local solutions and drew upon personal ethics rather than regulatory edicts to shape their responses. We argue that the importance of workplace relationships and informal channels for raising concerns should be better understood to help prevent the mistreatment of vulnerable groups.


Varicella vaccine studies in healthy children and adults.
Immunization of normal children and adults with Oka strain live varicella vaccine from several manufacturers has been studied in our laboratory and elsewhere. This paper summarizes clinical trials designed to obtain information on minimum dose immunogenicity pre- and postexposure prophylaxis, immunization of various age groups, and booster immunizations for seropositive individuals. These studies documented a 94% to 100% seroconversion rate with 95% to 100% persistence of antibodies at 3 to 4 years. Protective efficacy was more than 90%, and the vaccine was successful in preventing varicella when a high dose was given postexposure. Clinical reactions were limited to temperature elevations and minor papulovesicular rashes that occurred in 5% to 10% of vaccinees. Herpes zoster has been absent in vaccinated healthy individuals.