Relative Wage Movements and the Distribution of Consumption

We analyze how relative wage movements across birth cohorts and education groups during the 1980s affected the distribution of household consumption. The analysis integrates the labor economics literature on time variation in the wage structure with the consumption insurance literature. In contrast to previous tests of consumption insurance, we examine the impact of systematic, publicly observable shifts in the hourly wage structure. To circumvent the extreme scarcity of longitudinal data with high quality information on both consumption and labor market outcomes, we draw upon the best available cross-sectional data sources to construct synthetic panel data on consumption, labor supply and wages. We find that low-frequency movements in the cohort-education structure of pre-tax hourly wages drove large changes in the distribution of household consumption. The results constitute a spectacular failure of the consumption insurance hypothesis, and one that is not explained by existing theories of informationally constrained optimal consumption allocations. We also develop a procedure for assessing the welfare consequences of deviations from full consumption insurance and, in particular, from the failure to insulate the consumption distribution from relative wage shifts across cohort-education groups. For a coefficient of relative risk aversion equal to two, fully insulating households from group-specific endowment variation would raise welfare by an amount equivalent to a uniform 2.7% consumption increase.

The MRN complex in double-strand break repair and telomere maintenance

AbstractGenomes are subject to constant threat by damaging agents that generate DNA double-strand breaks (DSBs). The ends of linear chromosomes need to be protected from DNA damage recognition and end-joining, and this is achieved through protein–DNA complexes known as telomeres. The Mre11–Rad50–Nbs1 (MRN) complex plays important roles in detection and signaling of DSBs, as well as the repair pathways of homologous recombination (HR) and non-homologous end-joining (NHEJ). In addition, MRN associates with telomeres and contributes to their maintenance. Here, we provide an overview of MRN functions at DSBs, and examine its roles in telomere maintenance and dysfunction

Persistent neutrophil to lymphocyte ratio >3 during treatment with enzalutamide and clinical outcome in patients with castration-resistant prostate cancer

The baseline value of neutrophil to lymphocyte ratio (NLR) has been found to be prognostic in patients with metastatic castration resistant prostate cancer (CRPC). We evaluated the impact of baseline NLR and its change in patients receiving enzalutamide. We included consecutive metastatic CRPC patients treated with enzalutamide after docetaxel and studies the change of NLR (>3 vs ≤3) after week 4 and 12 weeks. Progression-free survival (PFS), overall survival (OS) and their 95% Confidence Intervals (95% CI) were estimated by the Kaplan-Meier method and compared with the log-rank test. The impact of NLR on PFS and OS was evaluated by Cox regression analyses and on prostate-specific antigen response rates (PSA RR; PSA decline >50%) were evaluated by binary logistic regression. Data collected on 193 patients from 9 centers were evaluated. Median age was 73.1 years (range, 42.8–90.7). The median baseline NLR was 3.2. The median PFS was 3.2 months (95% CI = 2.7–4.2) in patients with baseline NLR >3 and 7.4 months (95% CI = 5.5–9.7) in those with NLR ≤3, p < 0.0001. The median OS was 10.4 months (95% CI = 6.5–14.9) in patients with baseline NLR >3 and 16.9 months (95% CI = 11.2–20.9) in those with baseline NLR ≤3, p < 0.0001. In multivariate analysis, changes in NLR at 4 weeks were significant predictors of both PFS [hazard ratio (HR) 1.24, 95% confidence interval (95% CI) 1.07–1.42, p = 0.003, and OS (HR 1.29, 95% CI 1.10–1.51, p = 0.001. A persistent NLR >3 during treatment with enzalutamide seems to have both prognostic and predictive value in CRPC patients

Compliance with international guidelines for chronic inflammatory neuropathies

ERare diseases’ management guidelines are produced with the primary aim of improving practice and standards of care for patients and may represent a useful framework for clinical practice. The EFNS/PNS (European Federation of Neurological Societies/Peripheral Nerve Society) guidelines for CIDP (chronic inflammatory demyelinating polyneuropathy) and MMN (multifocal motor neuropathy) were last published in 2010 (1, 2). Enthusiasm of the audience for whom they are produced, arguably primarily non‐sub‐specialists, is however largely unexplored. Compliance to these guidelines by neuromuscular and/or peripheral nerve specialists has not been investigated

Organochlorine Chemical Residues in Northern Cardinal (Cardinalis cardinalis) Eggs from Greater Washington, DC USA

Northern Cardinal eggs from six neighborhoods near Washington DC were analyzed for organochlorine pesticides and PCBs. All compounds were detected more frequently and at higher concentrations in more heavily urbanized neighborhoods. DDT (mostly as p,pʹ-DDE) was detected in all neighborhoods. p,pʹ-DDT was typically 0.5‒16 ng/g (ww) in most suburban neighborhoods but was not detected (\u3c 0.1 ng/g) in more rural areas; however, p,pʹ-DDT was 127‒1130 ng/g in eggs from two suburban Maryland nests and comprised 65.7% of total p,pʹ-DDT isomers in the most contaminated sample, indicating recent exposure to un-weathered DDT. Total chlordane (sum of 5 compounds) was 2‒70 ng/g; concentrations were greatest in older suburban neighborhoods. Total PCB (sum of detected congeners) was \u3c 5‒21 ng/g. Congener patterns were similar in all neighborhoods and resembled those typical of weathered mixtures. Results indicate that wildlife remains exposed to low concentrations of legacy contaminants in suburban neighborhoods and that cardinal eggs can be used to monitor local- ized contamination

Immunosuppressant and immunomodulatory treatments for multifocal motor neuropathy

BACKGROUND: Multifocal motor neuropathy (MMN) is characterised by progressive, predominantly distal, asymmetrical limb weakness and usually multiple partial motor nerve conduction blocks. Intravenous immunoglobulin (IVIg) is beneficial but the role of immunosuppressive agents is uncertain. This is an update of a review first published in 2002 and previously updated in 2003, 2005, 2008 and 2011. OBJECTIVES: To assess the effects of immunosuppressive agents for the treatment of multifocal motor neuropathy. SEARCH METHODS: On 22 September 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE and LILACS for trials of MMN. We also searched two trials registers for ongoing studies. SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs) and quasi-RCTs. We considered prospective and retrospective case series and case reports in the Discussion. DATA COLLECTION AND ANALYSIS: Two review authors searched the titles and abstracts of the articles identified and extracted the data independently. MAIN RESULTS: Only one RCT of an immunosuppressive or immunomodulatory agent has been performed in MMN. This study randomised 28 participants and showed that mycophenolate mofetil, when used with IVIg, did not significantly improve strength, function or reduce the need for IVIg. No serious adverse events were observed. The study was deemed at low risk of bias. We summarised the results of retrospective and prospective case series in the discussion. AUTHORS' CONCLUSIONS: According to moderate quality evidence, mycophenolate mofetil did not produce significant benefit in terms of reducing need for IVIg or improving muscle strength in MMN. Trials of other immunosuppressants should be undertaken. Update of Immunosuppressant and immunomodulatory treatments for multifocal motor neuropathy

CRISPR-Cas9 Mediated Epitope Tagging Provides Accurate and Versatile Assessment of Myocardin

Objective- Unreliable antibodies often hinder the accurate detection of an endogenous protein, and this is particularly true for the cardiac and smooth muscle cofactor, MYOCD (myocardin). Accordingly, the mouse Myocd locus was targeted with 2 independent epitope tags for the unambiguous expression, localization, and activity of MYOCD protein. Approach and Results- 3cCRISPR (3-component clustered regularly interspaced short palindromic repeat) was used to engineer a carboxyl-terminal 3×FLAG or 3×HA epitope tag in mouse embryos. Western blotting with antibodies to each tag revealed a MYOCD protein product of ≈150 kDa, a size considerably larger than that reported in virtually all publications. MYOCD protein was most abundant in some adult smooth muscle-containing tissues with surprisingly low-level expression in the heart. Both alleles of Myocd are active in aorta because a 2-fold increase in protein was seen in mice homozygous versus heterozygous for FLAG-tagged Myocd. ChIP (chromatin immunoprecipitation)-quantitative polymerase chain reaction studies provide proof-of-principle data demonstrating the utility of this mouse line in conducting genome-wide ChIP-seq studies to ascertain the full complement of MYOCD-dependent target genes in vivo. Although FLAG-tagged MYOCD protein was undetectable in sections of adult mouse tissues, low-passaged vascular smooth muscle cells exhibited expected nuclear localization. Conclusions- This report validates new mouse models for analyzing MYOCD protein expression, localization, and binding activity in vivo and highlights the need for rigorous authentication of antibodies in biomedical research

CRISPR-Cas9 Mediated Epitope Tagging Provides Accurate and Versatile Assessment of Myocardin--Brief Report

OBJECTIVE: Unreliable antibodies often hinder the accurate detection of an endogenous protein, and this is particularly true for the cardiac and smooth muscle cofactor, MYOCD (myocardin). Accordingly, the mouse Myocd locus was targeted with 2 independent epitope tags for the unambiguous expression, localization, and activity of MYOCD protein. APPROACH AND RESULTS: 3cCRISPR (3-component clustered regularly interspaced short palindromic repeat) was used to engineer a carboxyl-terminal 3xFLAG or 3xHA epitope tag in mouse embryos. Western blotting with antibodies to each tag revealed a protein product of approximately 150 kDa, a size considerably larger than that reported in virtually all publications. MYOCD protein was most abundant in some adult smooth muscle-containing tissues with surprisingly low-level expression in the heart. Both alleles of Myocd are active in aorta because a 2-fold increase in protein was seen in mice homozygous versus heterozygous for FLAG-tagged Myocd. ChIP-quantitative polymerase chain reaction studies provide proof-of-principle data demonstrating the utility of this mouse line in conducting genome-wide ChIP-seq studies to ascertain the full complement of MYOCD-dependent target genes in vivo. Although FLAG-tagged MYOCD protein was undetectable in sections of adult mouse tissues, low-passaged vascular smooth muscle cells exhibited expected nuclear localization. CONCLUSIONS: This report validates new mouse models for analyzing MYOCD protein expression, localization, and binding activity in vivo and highlights the need for rigorous authentication of antibodies in biomedical research