What is the future of peer review? Why is there fraud in science? Is plagiarism out of control? Why do scientists do bad things? Is it all a case of:“All that is necessary for the triumph of evil is that good men do nothing?”

Peer review is an essential component of the process that is universally applied prior to the acceptance of a manuscript, grant or other scholarly work. Most of us willingly accept the responsibilities that come with being a reviewer but how comfortable are we with the process? Peer review is open to abuse but how should it be policed and can it be improved? A bad peer review process can inadvertently ruin an individual’s career, but are there penalties for policing a reviewer who deliberately sabotages a manuscript or grant? Science has received an increasingly tainted name because of recent high profile cases of alleged scientific misconduct. Once considered the results of work stress or a temporary mental health problem, scientific misconduct is increasingly being reported and proved to be a repeat offence. How should scientific misconduct be handled—is it a criminal offence and subject to national or international law? Similarly plagiarism is an ever-increasing concern whether at the level of the student or a university president. Are the existing laws tough enough? These issues, with appropriate examples, are dealt with in this review

Are We Over Oxidized? Oxidative Stress, Cardiovascular Disease, and the Future of Intervention Studies with Antioxidants

A number of recent clinical trials with antioxidants, notably vitamin C and E, have provided no support for the commonly held view that increasing our intake of antioxidants will offset the ravages of cardiovascular disease as well as other diseases (for extensive critical reviews see: Kritharides and Stocker 2002; Antoniades et al 2003; Touyz 2004). Is this conclusion justified? The role of antioxidant dietary adjuncts and therapy in prevention and treatment remains a highly important clinical question. In this opinion article we address the question: Is there a future for antioxidant therapy in the treatment and prevention of cardiovascular disease? We conclude that there is a need for better-designed studies as well as a re-thinking of the choice of antioxidants

3,5-Bis(ethoxy­carbon­yl)-2,6-dimethyl-1,4-dihydro­pyridine-4-carboxylic acid

The title mol­ecule, C14H19NO6, was synthesized by the reaction of glyoxylic acid, ethyl acetoacetate and NH4HCO3. In the crystal structure, the dihydro­pyridine ring adopts an asymmetric boat-type conformation with the C atom bearing the carboxyl group showing a signficantly larger deviation [0.325 (2) Å] from the base plane then the N atom [0.137 (2) Å]. One of the ethyl groups is disordered over two positions with occupancies of 0.741 (10) and 0.259 (10). The crystal is stabilized by strong inter­molecular hydrogen bonds. N—H⋯O inter­actions form infinite chains in the a direction. O—H⋯O hydrogen bonds form typical carboxylic acid dimers, which link the N—H⋯O chains into a ladder-type double chain

Primary structure and functional expression of a high voltage activated calcium channel from rabbit lung

The complete amino acid sequence of the receptor for organic calcium channel blockers (CaCB) from rabbit lung has been deduced by cloning and sequence analysis of the cDNA. Synthetic RNA derived from this cDNA induces the formation of a functional CaCB-sensitive high voltage activated calcium channel in Xenopus oocytes

Room for one more? A review of the literature on ‘inappropriate’ admissions to hospital for older people in the English NHS

This paper reports the findings of a review of the literature on emergency admissions to hospital for older people in the UK, undertaken between May and June 2014 at the Health Services Management Centre, University of Birmingham. This review sought to explore: the rate of in/appropriate emergency admissions of older people in the UK; the way this is defined in the literature; solutions proposed to reduce the rate of inappropriate admissions; and the methodological issues which particular definitions of ‘inappropriateness’ raise. The extent to which a patient perspective is included in these definitions of inappropriateness was also noted, given patient involvement is such a key policy priority in other areas of health policy. Despite long-standing policy debates, relatively little research has been published on formal rates of ‘inappropriate’ emergency hospital admissions for older people in the UK NHS in recent years. What has been produced indicates varying rates of in/appropriateness, inconsistent ways of defining appropriateness and a lack of focus on the possible solutions to address the problem. Significantly, patient perspectives are lacking, and we would suggest that this is a key factor in fully understanding how to prevent avoidable admissions. With an ageing population, significant financial challenges and a potentially fragmented health and social care system, the issue of the appropriateness of emergency admission is a pressing one which requires further research, greater focus on the experiences of older people and their families, and more nuanced contextual and evidence-based responses

Mirror-Image Packing Provides a Molecular Basis for the Nanomolar Equipotency of Enantiomers of an Experimental Herbicide

Programs of drug discovery generally exploit one enantiomer of a chiral compound for lead development following the principle that enantiomer recognition is central to biological specificity. However, chiral promiscuity has been identified for a number of enzyme families, which have shown that mirror-image packing can enable opposite enantiomers to be accommodated in an enzyme's active site. Reported here is a series of crystallographic studies of complexes between an enzyme and a potent experimental herbicide whose chiral center forms an essential part of the inhibitor pharmacophore. Initial studies with a racemate at 1.85 Å resolution failed to identify the chirality of the bound inhibitor, however, by extending the resolution to 1.1 Å and by analyzing high-resolution complexes with the enantiopure compounds, we determined that both enantiomers make equivalent pseudosymmetric interactions in the active site, thus mimicking an achiral reaction intermediate

Diethyl 4-[4-(dimethyl­amino)phen­yl]-2,6-dimethyl-1,4-dihydro­pyridine-3,5-dicarboxyl­ate

In the title compound, C21H28N2O4, the dihydro­pyridine ring adopts a flattened boat conformation. The mean plane of the dihydro­pyridine ring and the attached benzene ring form a dihedral angle of 85.1 (1) Å. One of two ethyl fragments is disordered between two conformations in a 0.67 (4):0.33 (4) ratio. In the crystal structure, mol­ecules related by translation along the a axis are linked into chains via inter­molecular N—H⋯O hydrogen bonds

Use of pyridinium ionic liquids as catalysts for the synthesis of 3,5-bis(dodecyloxycarbonyl)-1,4-dihydropyridine derivative

The synthesis of cationic amphiphilic 1,4-dihydropyridine derivative, potential gene delivery agent is achieved via an efficient multi-step sequence. The key step of this approach is a two-component Hantzsch type cyclisation of 3-oxo-2-[1-phenylmethylidene]-butyric acid dodecyl ester and 3-amino-but-2-enoic acid dodecyl ester utilising bis(2-hydroxyethyl)ether as a solvent and 1-butyl-4-methylpyridinium chloride as a catalyst. The 1,4-dihydropyridine derivative with long alkyl ester chains at positions 3 and 5 of the 1,4-DHP ring - 3,5-bis(dodecyloxycarbonyl)-2,6-dimethyl-4-phenyl-1,4-dihydropyridine was obtained in substantially higher yield with respect to classical Hantzsch synthesis. Bromination of this compound followed by nucleophilic substitution of bromine with pyridine gave the desired cationic amphiphilic 1,4-dihydropyridine.publishersversionPeer reviewe

Conformation of 1,4-dihydropyridine — planar or boat-like?

AbstractThe geometry of the 1,4-dihydropyridine molecule was completely optimized employing three different ab initio basis sets (6–31 G*, 4–31 G, STO—3G). The most reliable 6–31G* basis set provides a very flat boat conformation which may easily undergo defolding to a planar ring arrangement. This result is discussed with respect to enzymatic redox cofactors and the pharmacological activity of dihydropyridine calcium antagonists