Hearing-Aid Safety: A Comparison of Estimated Threshold Shifts for Gains Recommended by Nal-Nl2 and Dsl M[i/O] Prescriptions for Children

Objective: To investigate the predicted threshold shift associated with the use of nonlinear hearing aids fitted to the NAL-NL2 or the DSL m[i/o] prescription for children with the same audiograms. For medium and high input levels, we asked: (1) How does predicted asymptotic threshold shifts (ATS) differ according to the choice of prescription? (2) How does predicted ATS vary with hearing level for gains prescribed by the two prescriptions? Design: A mathematical model consisting of the modified power law combined with equations for predicting temporary threshold shift (Macrae, 1994b) was used to predict ATS. Study sample: Predicted threshold shift were determined for 57 audiograms at medium and high input levels. Results: For the 57 audiograms, DSL m[i/o] gains for high input levels were associated with increased risk relative to NAL-NL2. The variation of ATS with hearing level suggests that NAL-NL2 gains became unsafe when hearing loss \u3e 90 dB HL. The gains prescribed by DSL m[i/o] became unsafe when hearing loss \u3e 80 dB HL at a medium input level, and \u3e 70 dB HL at a high input level. Conclusion: There is a risk of damage to hearing for children using nonlinear amplification. Vigilant checking for threshold shift is recommended

Reply: Screening for colorectal cancer with immunological FOBT

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Analytical modeling and sensor monitoring for optimal processing of advanced textile structural composites by resin transfer molding

A two-dimensional model of the resin transfer molding (RTM) process was developed which can be used to simulate the infiltration of resin into an anisotropic fibrous preform. Frequency dependent electromagnetic sensing (FDEMS) has been developed for in situ monitoring of the RTM process. Flow visualization tests were performed to obtain data which can be used to verify the sensor measurements and the model predictions. Results of the tests showed that FDEMS can accurately detect the position of the resin flow-front during mold filling, and that the model predicted flow-front patterns agreed well with the measured flow-front patterns

4-[(E)-2-Ferrocenylethen­yl]-1,8-naphthalic anhydride

In the structure of the title compound, [Fe(C5H5)(C19H11O3)], the plane of the substituted ferrocene ring is tilted by 14.17 (6)° with respect to the mean plane through the naphthalene ring system. In the crystal structure, centrosymmetric dimers are formed through π–π inter­actions [centroid–centroid distance = 3.624 (2) Å] between the substituted ferrocene ring and the three fused rings of the naphthalic anhydride unit. Pairs of dimers are held together by further naphthalene–naphthalene π–π interactions [distance between parallel mean planes 3.45 (3) Å]. Each dimer inter­acts with four neighbouring dimers in a herringbone fashion through C—H⋯π inter­actions, so forming a two-dimensional sheet-like structure

The human squamous oesophagus has widespread capacity for clonal expansion from cells at diverse stages of differentiation.

OBJECTIVE: Knowledge of the cellular mechanisms involved in homeostasis of human squamous oesophagus in the steady state and following chronic injury is limited. We aimed to better understand these mechanisms by using a functional 3D approach. DESIGN: Proliferation, mitosis and the expression of progenitor lineage markers were assessed in normal squamous oesophagus from 10 patients by immunofluorescence on 3D epithelial whole mounts. Cells expressing differential levels of epithelial and progenitor markers were isolated using flow cytometry sorting and characterised by qPCR and IF. Their self-renewing potential was investigated by colony forming cells assays and in vitro organotypic culture models. RESULTS: Proliferation and mitotic activity was highest in the interpapillary basal layer and decreased linearly towards the tip of the papilla (p<0.0001). The orientation of mitosis was random throughout the basal layer, and asymmetric divisions were not restricted to specific cell compartments. Cells sorted into distinct populations based on the expression of epithelial and progenitor cell markers (CD34 and EpCAM) showed no difference in self-renewal in 2D culture, either as whole populations or as single cells. In 3D organotypic cultures, all cell subtypes were able to recapitulate the architecture of the tissue of origin and the main factor determining the success of the 3D culture was the number of cells plated, rather than the cell type. CONCLUSIONS: Oesophageal epithelial cells demonstrate remarkable plasticity for self-renewal. This situation could be viewed as an ex vivo wounding response and is compatible with recent findings in murine models

A network of Rab GTPases controls phagosome maturation and is modulated by Salmonella enterica serovar Typhimurium

Members of the Rab guanosine triphosphatase (GTPase) family are key regulators of membrane traffic. Here we examined the association of 48 Rabs with model phagosomes containing a non-invasive mutant of Salmonella enterica serovar Typhimurium (S. Typhimurium). This mutant traffics to lysosomes and allowed us to determine which Rabs localize to a maturing phagosome. In total, 18 Rabs associated with maturing phagosomes, each with its own kinetics of association. Dominant-negative mutants of Rab23 and 35 inhibited phagosome–lysosome fusion. A large number of Rab GTPases localized to wild-type Salmonella-containing vacuoles (SCVs), which do not fuse with lysosomes. However, some Rabs (8B, 13, 23, 32, and 35) were excluded from wild-type SCVs whereas others (5A, 5B, 5C, 7A, 11A, and 11B) were enriched on this compartment. Our studies demonstrate that a complex network of Rab GTPases controls endocytic progression to lysosomes and that this is modulated by S. Typhimurium to allow its intracellular growth

Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22

A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI)-high tumors, or no evidence of linkage to MMR genes). Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR), the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected) were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLOD = 4.51, α = 0.84, 145.40 cM, rs10518142) and among all families at 12q24.32 (dominant HLOD = 3.60, α = 0.48, 285.15 cM, rs952093). Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD = 3.07, α = 0.29; dominant HLOD = 3.03, α = 0.32, respectively). Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD = 3.02, α = 0.51, 132.52 cM, rs1319036). These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated. © 2012 Cicek et al

Diagnostic performance of the IMMY cryptococcal antigen lateral flow assay on serum and cerebrospinal fluid for diagnosis of cryptococcosis in HIV-negative patients: a systematic review.

BACKGROUND: The incidence of cryptococcosis amongst HIV-negative persons is increasing. Whilst the excellent performance of the CrAg testing in people living with HIV is well described, the diagnostic performance of the CrAg LFA has not been systematically evaluated in HIV-negative cohorts on serum or cerebrospinal fluid. METHODS: We performed a systematic review to characterise the diagnostic performance of IMMY CrAg® LFA in HIV-negative populations on serum and cerebrospinal fluid. A systematic electronic search was performed using Medline, Embase, Global Health, CENTRAL, WoS Science Citation Index, SCOPUS, Africa-Wide Information, LILACS and WHO Global Health Library. Studies were screened and data extracted from eligible studies by two independent reviewers. A fixed effect meta-analysis was used to estimate the diagnostic sensitivity and specificity. RESULTS: Of 447 records assessed for eligibility, nine studies met our inclusion criteria, including 528 participants overall. Amongst eight studies that evaluated the diagnostic performance of the IMMY CrAg® LFA on serum, the pooled median sensitivity was 96% (95% Credible Interval (CrI) 68-100%) with a pooled specificity estimate of 96% (95%CrI 84-100%). Amongst six studies which evaluated the diagnostic performance of IMMY CrAg® LFA on CSF, the pooled median sensitivity was 99% (95%CrI 95-100%) with a pooled specificity median of 99% (95%CrI 95-100%). CONCLUSIONS: This review demonstrates a high pooled sensitivity and specificity for the IMMY CrAg® LFA in HIV-negative populations, in keeping with findings in HIV-positive individuals. The review was limited by the small number of studies. Further studies using IMMY CrAg® LFA in HIV-negative populations would help to better determine the diagnostic value of this test