Human CD141(+) (BDCA-3)(+) dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens

The characterization of human dendritic cell (DC) subsets is essential for the design of new vaccines. We report the first detailed functional analysis of the human CD141(+) DC subset. CD141(+) DCs are found in human lymph nodes, bone marrow, tonsil, and blood, and the latter proved to be the best source of highly purified cells for functional analysis. They are characterized by high expression of toll-like receptor 3, production of IL-12p70 and IFN-beta, and superior capacity to induce T helper 1 cell responses, when compared with the more commonly studied CD1c(+) DC subset. Polyinosine-polycytidylic acid (poly I:C)-activated CD141(+) DCs have a superior capacity to cross-present soluble protein antigen (Ag) to CD8(+) cytotoxic T lymphocytes than poly I:C-activated CD1c(+) DCs. Importantly, CD141(+) DCs, but not CD1c(+) DCs, were endowed with the capacity to cross-present viral Ag after their uptake of necrotic virus-infected cells. These findings establish the CD141(+) DC subset as an important functionally distinct human DC subtype with characteristics similar to those of the mouse CD8 alpha(+) DC subset. The data demonstrate a role for CD141(+) DCs in the induction of cytotoxic T lymphocyte responses and suggest that they may be the most relevant targets for vaccination against cancers, viruses, and other pathogens.

Z-source converter based grid-interface for variable-speed permanent magnet wind turbine generators

A Z-source inverter based grid-interface for a variable-speed wind turbine connected to a permanent magnet synchronous generator is proposed. A control system is designed to harvest maximum wind energy under varied wind conditions with the use of the permanent magnet synchronous generator, diode-rectifier and Z-source inverter. Control systems for speed regulation of the generator and for DC- and AC- sides of the Z-source inverter are investigated using computer simulations and laboratory experiments. Simulation and experimental results verify the efficacy of the proposed approach.

Mandatory Reporting Laws and Identification of Child Abuse and Neglect: Consideration of Differential Maltreatment Types, and a Cross-Jurisdictional Analysis of Child Sexual Abuse Reports

Mandatory reporting laws have been created in many jurisdictions as a way of identifying cases of severe child maltreatment on the basis that cases will otherwise remain hidden. These laws usually apply to all four maltreatment types. Other jurisdictions have narrower approaches supplemented by differential response systems, and others still have chosen not to enact mandatory reporting laws for any type of maltreatment. In scholarly research and normative debates about mandatory reporting laws and their effects, the four major forms of child maltreatment—physical abuse, sexual abuse, emotional abuse, and neglect—are often grouped together as if they are homogenous in nature, cause, and consequence. Yet, the heterogeneity of maltreatment types, and different reporting practices regarding them, must be acknowledged and explored when considering what legal and policy frameworks are best suited to identify and respond to cases. A related question which is often conjectured upon but seldom empirically explored, is whether reporting laws make a difference in case identification. This article first considers different types of child abuse and neglect, before exploring the nature and operation of mandatory reporting laws in different contexts. It then posits a differentiation thesis, arguing that different patterns of reporting between both reporter groups and maltreatment types must be acknowledged and analysed, and should inform discussions and assessments of optimal approaches in law, policy and practice. Finally, to contribute to the evidence base required to inform discussion, this article conducts an empirical cross-jurisdictional comparison of the reporting and identification of child sexual abuse in jurisdictions with and withoutmandatory reporting, and concludes that mandatory reporting laws appear to be associated with better case identification.

Cross cultural adaptation and validation of a Spanish version of the lower limb functional index

Background: The Lower Limb Functional Index (LLFI) is a relatively recently published regional outcome measure. The development article showed the LLFI had robust and valid clinimetric properties with sound psychometric and practical characteristics when compared to the Lower Limb Extremity Scale (LEFS) criterion standard. Objective: The purpose of this study was cross cultural adaptation and validation of the LLFI Spanish-version (LLFI-Sp) in a Spanish population. Methods: A two stage observational study was conducted. The LLFI was initially cross-culturally adapted to Spanish through double forward and single backward translation; then subsequently validated for the psychometric characteristics of validity, internal consistency, reliability, error score and factor structure. Participants (n = 136) with various lower limb conditions of >12 weeks duration completed the LLFI-Sp, Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and the Euroqol Health Questionnaire 5 Dimensions (EQ-5D-3 L). The full sample was employed to determine internal consistency, concurrent criterion validity, construct validity and factor structure; a subgroup (n = 45) determined reliability at seven days concurrently completing a global rating of change scale. Results: The LLFI-Sp demonstrated high but not excessive internal consistency (α = 0.91) and high reliability (ICC = 0.96). The factor structure was one-dimensional which supported the construct validity. Criterion validity with the WOMAC was strong (r = 0.77) and with the EQ-5D-3 L fair and inversely correlated (r = -0.62). The study limitations included the lack of longitudinal data and the determination of responsiveness. Conclusions: The LLFI-Sp supports the findings of the original English version as being a valid lower limb regional outcome measure. It demonstrated similar psychometric properties for internal consistency, validity, reliability, error score and factor structure.

Biceps femoris long-head architecture: A reliability and retrospective injury study

Purpose: To determine i) the reliability of two-dimensional ultrasonography for the assessment of biceps femoris long head (BFlh) architectural characteristics; ii) if limbs with a history of strain injury in the BFlh display different architecture and eccentric strength compared to uninjured limbs. Methods: This case-control study (control [n=20], injured group [n=16], males) assessed the BFlh architecture at rest and during graded isometric contractions using two-dimensional ultrasonography. The control group were assessed three times (>24hrs apart) to determine reliability. Previously injured individuals were evaluated once. Results The assessment of BFlh architecture was highly reliable (intraclass correlations >0.90). Fascicle length (p<0.001; d range: 0.67 to 1.34) and fascicle length relative to muscle thickness (p<0.001; d range: 0.58 to 0.85) of the previously injured BFlh were significantly less than the contralateral uninjured BFlh at all intensities. Pennation angle of the previously injured BFlh was significantly greater (p<0.001; d range: 0.62 to 0.88) than the contralateral uninjured BFlh at all intensities. Eccentric strength in the previously injured limb was significantly lower than the contralateral limb (-15.4%; -52.5N; 95% CI=-28.45 to -76.23; p<0.001, d=0.56). Conclusion These data indicate that two-dimensional ultrasonography is reliable for assessing BFlh architecture at rest and during graded isometric contractions. Fascicle length, fascicle length relative to muscle thickness and pennation angle are significantly different in previously injured BFlh compared to an uninjured contralateral BFlh. Eccentric strength of the previously injured limb is also significantly lower than the uninjured contralateral limb. These findings have implications for rehabilitation and injury prevention practices which should consider altered architectural characteristics.

Influence of visible work activity on drivers’ speed choice at roadworks

Vehicle traffic through roadwork sites creates a hazardous work environment, with speed limit noncompliance a major contributor to the high risk and high severity of roadwork crashes. This paper examines responses to an online survey to better understand the factors underlying drivers’ work zone speed choices. Drivers’ stated speed choice was compared between two photographs of the same work zone section – one with workers and machinery present and another with no visible activity. Drivers also provided comments on any aspect of roadwork safety they thought was important. A paired t-test of stated speed choice revealed that significantly lower mean speeds were nominated when workers and machinery were clearly present and active (41.7 vs 53.5 km/h, p<0.01). Participants expressed concern about roadwork signage and reduced speed limits being left in place when there was no apparent work activity. Driver perceptions, and thus compliance, may be improved through technological and operational changes.

Queensland flood waters head south

AN explanation of the path of flood waters that have surged east and south west in southern Queensland. CREDITS: Audio by Amanda Gearing

Burglar target selection : a cross-national comparison

Objectives This study builds on research undertaken by Bernasco and Nieuwbeerta and explores the generalizability of a theoretically derived offender target selection model in three cross-national study regions. Methods Taking a discrete spatial choice approach, we estimate the impact of both environment- and offender-level factors on residential burglary placement in the Netherlands, the United Kingdom, and Australia. Combining cleared burglary data from all study regions in a single statistical model, we make statistical comparisons between environments. Results In all three study regions, the likelihood an offender selects an area for burglary is positively influenced by proximity to their home, the proportion of easily accessible targets, and the total number of targets available. Furthermore, in two of the three study regions, juvenile offenders under the legal driving age are significantly more influenced by target proximity than adult offenders. Post hoc tests indicate the magnitudes of these impacts vary significantly between study regions. Conclusions While burglary target selection strategies are consistent with opportunity-based explanations of offending, the impact of environmental context is significant. As such, the approach undertaken in combining observations from multiple study regions may aid criminology scholars in assessing the generalizability of observed findings across multiple environments.

Cross-cultural adaptation, reliability and validity of the Spanish version of the upper limb functional index

Background The Upper Limb Functional Index (ULFI) is an internationally widely used outcome measure with robust, valid psychometric properties. The purpose of study is to develop and validate a ULFI Spanish-version (ULFI-Sp). Methods A two stage observational study was conducted. The ULFI was cross-culturally adapted to Spanish through double forward and backward translations, the psychometric properties were then validated. Participants (n = 126) with various upper limb conditions of >12 weeks duration completed the ULFI-Sp, QuickDASH and the Euroqol Health Questionnaire 5 Dimensions (EQ-5D-3 L). The full sample determined internal consistency, concurrent criterion validity, construct validity and factor structure; a subgroup (n = 35) determined reliability at seven days. Results The ULFI-Sp demonstrated high internal consistency (α = 0.94) and reliability (r = 0.93). Factor structure was one-dimensional and supported construct validity. Criterion validity with the EQ-5D-3 L was fair and inversely correlated (r = −0.59). The QuickDASH data was unavailable for analysis due to excessive missing responses. Conclusions The ULFI-Sp is a valid upper limb outcome measure with similar psychometric properties to the English language version.

Demonstration of regulatory cross-talk between P fimbriae and type 1 fimbriae in uropathogenic Escherichia coli

The majority of Escherichia coli strains isolated from urinary tract infections have the potential to express multiple fimbriae. Two of the most common fimbrial adhesins are type 1 fimbriae and pyelonephritis-associated pili (Pap). Previous research has shown that induced, plasmid-based expression of a Pap regulator, papB, and its close homologues can prevent inversion of the fim switch controlling the expression of type 1 fimbriae. The aim of the present study was to determine if this cross-regulation occurs when PapB is expressed from its native promoter in the chromosome of E. coli K-12 and clinical isolates. The regulation was examined in three ways: (1) mutated alleles of the pap regulatory region, including papB and papI, that maintain the pap promoter in either the off or the on phase were exchanged into the chromosome of both E. coli K-12 and the clinical isolate E. coli CFT073, and the effect on type 1 fimbrial expression was measured; (2) type 1 fimbrial expression was determined using a novel fimS : : gfp+ reporter system in mutants of the clinical isolate E. coli 536 in which combinations of complete fimbrial clusters had been deleted; (3) type 1 fimbrial expression was determined in a range of clinical isolates and compared with both the number of P clusters and their expression. All three approaches demonstrated that P expression represses type 1 fimbrial expression. Using a number of novel genetic approaches, this work extends the initial finding that PapB inhibits FimB recombination to the impact of this regulation in clinical isolates.

Association of CYP1B1 codon 432 mutant allele in head and neck squamous cell cancer is reflected by somatic mutations of p53 in tumor tissue

Tobacco use is causally associated with head and neck squamous cell cancer (HNSCC). Here, we present the results of a case-control study that investigated the effects that the genetic variants of the cytochrome (CYP)1A1, CYP1B1, glutathione-S-transferase (GST)M1, GSTT1, and GSTP1 genes have on modifying the risk of smoking-related HNSCC. Allelisms of the CYP1A1, GSTT1, GSTM1, and GSTT1 genes alone were not associated with an increased risk. CYP1B1 codon 432 polymorphism was found to be a putative susceptibility factor in smoking-related HNSCC. The frequency of CYP1B1 polymorphism was significantly higher (P < 0.001) in the group of smoking cases when compared with smoking controls. Additionally, an odds ratio (OR) of 4.53 (2.62-7.98) was discovered when investigating smoking and nonsmoking cases for the susceptible genotype CYP1B1*2/*2, when compared with the presence of the genotype wild type. In combination with polymorphic variants of the GST genes, a synergistic-effect OR was observed. The calculated OR for the combined genotype CYP1B1*2/*2 and GSTM1*2/*2 was 12.8 (4.09-49.7). The calculated OR for the combined genotype was 13.4 (2.92-97.7) for CYP1B1*2/*2 and GSTT1*2/*2, and 24.1 (9.36-70.5) for the combination of CYP1B1*2/*2 and GSTT1-expressors. The impact of the polymorphic variants of the CYP1B1 gene on HNSCC risk is reflected by the strong association with the frequency of somatic mutations of the p53 gene. Smokers with susceptible genotype CYP1B1*2/*2 were 20 times more likely to show evidence of p53 mutations than were those with CYP1B1 wild type. Combined genotype analysis of CYP1B1 and GSTM1 or GSTT1 revealed interactive effects on the occurrence of p53 gene mutations. The results of the present study indicate that polymorphic variants of CYP1B1 relate significantly to the individual susceptibility of smokers to HNSCC.

Cytochrome p450 1b1, a new keystone in gene-environment interactions related to human head and neck cancer?

Alcohol consumption and tobacco smoking are major causes of head and neck cancers, and regional differences point to the importance of research into gene-environment interactions. Much interest has been focused on polymorphisms of CYP1A1 and of GSTM1 and GSTT1, but a number of studies have not demonstrated significant effects. This has mostly been ascribed to small sample sizes. In general, the impact of polymorphisms of metabolic enzymes appears inconsistent, with some reports of weak-to-moderate associations, and with others of no elevation of risks. The classical cytochrome P450 isoenzyme considered for metabolic activation of polycyclic aromatic hydrocarbons (PAH) is CYP1A1. A new member of the CYP1 family, CYP1B1, was cloned in 1994, currently representing the only member of the CYP1B subfamily. A number of single nucleotide polymorphisms of the CYP1B1 gene have been reported. The amino acid substitutions Val432Leu (CYP1B1*3) and Asn453Ser (CYP1B1*4), located in the heme binding domain of CYP1B1, appear as likely candidates to be linked with biological effects. CYP1B1 activates a wide range of PAH, aromatic and heterocyclic amines. Very recently, the CYP1B1 codon 432 polymorphism (CYP1B1*3) has been identified as a susceptibility factor in smoking-related head-and-neck squamous cell cancer. The impact of this polymorphic variant of CYP1B1 on cancer risk was also reflected by an association with the frequency of somatic mutations of the p53 gene. Combined genotype analysis of CYP1B1 and the glutathione transferases GSTM1 or GSTT1 has pointed to interactive effects. This provides new molecular evidence that tobacco smoke-specific compounds relevant to head and neck carcinogenesis are metabolically activated through CYP1B1 and is consistent with a major pathogenetic relevance of PAH as ingredients of tobacco smoke.