Going-Concern Opinions: Broadening the Expectations Gap

A rash of high-profile bankruptcies has led to a search for answers. Many hold auditors responsible for not detecting the potential for bankruptcy during the most recent audit. The Weiss Report, a study of several dozen bankrupt companies submitted to the U.S. Senate during its deliberations on the Sarbanes-Oxley Act, found a broad and massive failure on the part of auditors to raise yellow flags that indicate potential bankruptcy. The authors examined Weiss\u27 methodology and found that, applied to a broader group of companies, Weiss\u27 criteria would have incorrectly predicted bankruptcy for nearly half of the non-bankrupt companies studied. This failure to accurately predict undermines the credibility of the subsequently enacted legislation

Oligonucleotide Based Magnetic Bead Capture of Onchocerca volvulus DNA for PCR Pool Screening of Vector Black Flies

The absence of infective larvae of Onchocerca volvulus in the black fly vector of this parasite is a major criterion used to certify that transmission has been eliminated in a focus. This process requires screening large numbers of flies. Currently, this is accomplished by screening pools of flies using a PCR-based assay. The number of flies that may be included in each pool is currently limited by the DNA purification process to 50 flies for Latin American vectors and 100 flies for African vectors. Here, we describe a new method for DNA purification that relies upon a specific oligonucleotide to capture and immobilize the parasite DNA on a magnetic bead. This method permits the reliable detection of a single infective larva of O. volvulus in pools containing up to 200 individual flies. The method described here will dramatically improve the efficiency of pool screening of vector black flies, making the process of elimination certification easier and less expensive to implement

Design, Analysis and Testing of a Novel Mitral Valve for Transcatheter Implantation

Mitral regurgitation is a common mitral valve dysfunction which may lead to heart failure. Because of the rapid aging of the population, conventional surgical repair and replacement of the pathological valve are often unsuitable for about half of symptomatic patients, who are judged high-risk. Transcatheter valve implantation could represent an effective solution. However, currently available aortic valve devices are inapt for the mitral position. This paper presents the design, development and hydrodynamic assessment of a novel bi-leaflet mitral valve suitable for transcatheter implantation. The device consists of two leaflets and a sealing component made from bovine pericardium, supported by a self-expanding wireframe made from superelastic NiTi alloy. A parametric design procedure based on numerical simulations was implemented to identify design parameters providing acceptable stress levels and maximum coaptation area for the leaflets. The wireframe was designed to host the leaflets and was optimised numerically to minimise the stresses for crimping in an 8 mm sheath for percutaneous delivery. Prototypes were built and their hydrodynamic performances were tested on a cardiac pulse duplicator, in compliance with the ISO5840-3:2013 standard. The numerical results and hydrodynamic tests show the feasibility of the device to be adopted as a transcatheter valve implant for treating mitral regurgitation

Phenotypic Complexity, Measurement Bias, and Poor Phenotypic Resolution Contribute to the Missing Heritability Problem in Genetic Association Studies

Background The variance explained by genetic variants as identified in (genome-wide) genetic association studies is typically small compared to family-based heritability estimates. Explanations of this ‘missing heritability’ have been mainly genetic, such as genetic heterogeneity and complex (epi-)genetic mechanisms. Methodology We used comprehensive simulation studies to show that three phenotypic measurement issues also provide viable explanations of the missing heritability: phenotypic complexity, measurement bias, and phenotypic resolution. We identify the circumstances in which the use of phenotypic sum-scores and the presence of measurement bias lower the power to detect genetic variants. In addition, we show how the differential resolution of psychometric instruments (i.e., whether the instrument includes items that resolve individual differences in the normal range or in the clinical range of a phenotype) affects the power to detect genetic variants. Conclusion We conclude that careful phenotypic data modelling can improve the genetic signal, and thus the statistical power to identify genetic variants by 20-99

Italian guidelines for primary headaches: 2012 revised version

The first edition of the Italian diagnostic and therapeutic guidelines for primary headaches in adults was published in J Headache Pain 2(Suppl. 1):105–190 (2001). Ten years later, the guideline committee of the Italian Society for the Study of Headaches (SISC) decided it was time to update therapeutic guidelines. A literature search was carried out on Medline database, and all articles on primary headache treatments in English, German, French and Italian published from February 2001 to December 2011 were taken into account. Only randomized controlled trials (RCT) and meta-analyses were analysed for each drug. If RCT were lacking, open studies and case series were also examined. According to the previous edition, four levels of recommendation were defined on the basis of levels of evidence, scientific strength of evidence and clinical effectiveness. Recommendations for symptomatic and prophylactic treatment of migraine and cluster headache were therefore revised with respect to previous 2001 guidelines and a section was dedicated to non-pharmacological treatment. This article reports a summary of the revised version published in extenso in an Italian version

Concentration-Discharge Patterns Reveal Catchment Controls Over the Stoichiometry of Carbon and Nutrient Supply to Boreal Streams

Carbon (C), nitrogen (N), and phosphorus (P) export from catchments is strongly regulated by interactions between hydrological flowpaths and their terrestrial use/storage. While concentration-discharge (c-Q) relationships have been widely used to understand this interplay for C, N, and P individually, how flow regulates the relative supply of these resources across spatial and temporal scales is not well documented. Here, we analyze c-Q relationships from 12 years of data to test how seasonal flow regulates the concentrations of inorganic N (Dissolved inorganic nitrogen [DIN]) and P (Dissolved inorganic phosphorus [DIP]), dissolved organic N (DON) and C (dissolved organic carbon [DOC]) and their respective ratios across 12 streams in a boreal landscape. We observed opposing c-Q relationships between organic and inorganic solutes. DOC and DON tended toward transport limitation with little year-to-year change, whereas ammonium (NH4) and DIP were increasingly source limited over time. These different c-Q relationships translated into large (up to three-fold) shifts in resource ratios (e.g., DOC:DIN) in response to changes in flow. Our results also highlight strong influences of catchment structure on c-Q patterns, regardless of solute, season, and longer-term directional changes. Here, the organic solute c-Q responses became less transport limited over time; while inorganic solute responses became less source limited with increasing mire/decreasing forest cover. Overall, differences in timing of catchment exports for C, N, and P, create dynamic variation in solute concentrations in streams with subsequent impacts on resource stoichiometry that is central to aquatic ecological processes

Concentration-discharge patterns reveal catchment controls over the stoichiometry of carbon and nutrient supply to boreal streams

Carbon (C), nitrogen (N), and phosphorus (P) export from catchments is strongly regulated by interactions between hydrological flowpaths and their terrestrial use/storage. While concentration-discharge (c-Q) relationships have been widely used to understand this interplay for C, N, and P individually, how flow regulates the relative supply of these resources across spatial and temporal scales is not well documented. Here, we analyze c-Q relationships from 12 years of data to test how seasonal flow regulates the concentrations of inorganic N (Dissolved inorganic nitrogen [DIN]) and P (Dissolved inorganic phosphorus [DIP]), dissolved organic N (DON) and C (dissolved organic carbon [DOC]) and their respective ratios across 12 streams in a boreal landscape. We observed opposing c-Q relationships between organic and inorganic solutes. DOC and DON tended toward transport limitation with little year-to-year change, whereas ammonium (NH4) and DIP were increasingly source limited over time. These different c-Q relationships translated into large (up to three-fold) shifts in resource ratios (e.g., DOC:DIN) in response to changes in flow. Our results also highlight strong influences of catchment structure on c-Q patterns, regardless of solute, season, and longer-term directional changes. Here, the organic solute c-Q responses became less transport limited over time; while inorganic solute responses became less source limited with increasing mire/decreasing forest cover. Overall, differences in timing of catchment exports for C, N, and P, create dynamic variation in solute concentrations in streams with subsequent impacts on resource stoichiometry that is central to aquatic ecological processes

Dopamine targets cycling B cells independent of receptors/transporter for oxidative attack: Implications for non-Hodgkin’s lymphoma

Human B lymphocytes and derived lines from a spectrum of B cell malignancy were studied for expression of dopaminergic pathway components and for their cytostatic response to the catecholamine and related, potentially therapeutic compounds. Proliferating normal lymphocytes and dividing malignant clones rapidly arrested on exposure to dopamine in the low (≤10 μM) micromolar range. The antiparkinsonian drugs l-DOPA and apomorphine (particularly) were similarly antiproliferative. With the exception of D4, dopamine receptors D1–D5 were variably expressed among normal and neoplastic B cell populations, as was the dopamine transporter. Transcripts for D1 and D2 were frequently found, whereas D3 and D5 revealed restricted expression; dopamine transporter was detected in most cases. Nevertheless, pharmacological analysis disclosed that dopamine targeted cycling B cells independent of these structures. Rather, oxidative stress constituted the primary mechanism: the catecholamine’s actions being mimicked by hydrogen peroxide and reversed by exogenous catalase, and evidence for the intracellular redox protein thioredoxin contributing protection. Among proliferating clones, growth arrest was accompanied by cell death in populations deplete in antiapoptotic Bcl-2: resting lymphocytes escaping low micromolar dopamine toxicity. Dysregulated bcl-2 expression, although preventing oxidative-induced caspase-dependent apoptosis, by itself conferred only minor protection against dopamine cytostasis. The selective impact of dopamine on lymphocytes that are in active cycle indicates an axis for therapeutic intervention not only in B cell neoplasia but also in lymphoproliferative disturbances generally. Rational tailoring of drug delivery systems already in development for Parkinson’s disease could provide ideal vehicles for carrying the oxidative hit directly to the target populations

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease