Can screening and brief intervention lead to population-level reductions in alcohol-related harm?

A distinction is made between the clinical and public health justifications for screening and brief intervention (SBI) against hazardous and harmful alcohol consumption. Early claims for a public health benefit of SBI derived from research on general medical practitioners' (GPs') advice on smoking cessation, but these claims have not been realized, mainly because GPs have not incorporated SBI into their routine practice. A recent modeling exercise estimated that, if all GPs in England screened every patient at their next consultation, 96% of the general population would be screened over 10 years, with 70-79% of excessive drinkers receiving brief interventions (BI); assuming a 10% success rate, this would probably amount to a population-level effect of SBI. Thus, a public health benefit for SBI presupposes widespread screening; but recent government policy in England favors targeted versus universal screening, and in Scotland screening is based on new registrations and clinical presentation. A recent proposal for a national screening program was rejected by the UK National Health Service's National Screening Committee because 1) there was no good evidence that SBI led to reductions in mortality or morbidity, and 2) a safe, simple, precise, and validated screening test was not available. Even in countries like Sweden and Finland, where expensive national programs to disseminate SBI have been implemented, only a minority of the population has been asked about drinking during health-care visits, and a minority of excessive drinkers has been advised to cut down. Although there has been research on the relationship between treatment for alcohol problems and population-level effects, there has been no such research for SBI, nor have there been experimental investigations of its relationship with population-level measures of alcohol-related harm. These are strongly recommended. In this article, conditions that would allow a population-level effect of SBI to occur are reviewed, including their political acceptability. It is tentatively concluded that widespread dissemination of SBI, without the implementation of alcohol control measures, might have indirect influences on levels of consumption and harm but would be unlikely on its own to result in public health benefits. However, if and when alcohol control measures were introduced, SBI would still have an important role in the battle against alcohol-related harm

Interpopulation crosses, inheritance study, and genetic variability in the brown planthopper complex, Nilaparvata lugens (Homoptera: Delphacidae)

Studies on hybridization, inheritance, and population genetics of brown planthoppers that infest rice and weeds were undertaken using starch gel electrophoresis to determine whether the weed-infesting population represents a biological race or a species. F(1) and F(2) generations were produced by crosses between parental insects from the two populations with little indication of hybrid sterility. Gpi, Mdh, and Idh loci were inherited in a simple Mendelian fashion in families of two sympatric populations. Sixteen populations of Nilaparvata spp. from eight locations were collected. The Mdh, Idh, Pgm, Gpi, 6Pgd, and Acp loci were polymorphic. The N. lugens of rice with high esterase activity were clustered into a group and characterized by the presence of alleles Gpi (110) and Gpi (120), whereas N. lugens from weeds with low esterase activity were clustered into another group and characterized by Gpi (100) and Gpi (90) . There was a lack of heterozygotes between the common alleles of the two populations. This means that the two groups of individuals belong to different gene pools

Conformational Space and Stability of ETD Charge Reduction Products of Ubiquitin

Owing to its versatility, electron transfer dissociation (ETD) has become one of the most commonly utilized fragmentation techniques in both native and non-native top-down mass spectrometry. However, several competing reactions—primarily different forms of charge reduction—occur under ETD conditions, as evidenced by the distorted isotope patterns usually observed. In this work, we analyze these isotope patterns to compare the stability of nondissociative electron transfer (ETnoD) products, specifically noncovalent c/z fragment complexes, across a range of ubiquitin conformational states. Using ion mobility, we find that more extended states are more prone to fragment release. We obtain evidence that for a given charge state, populations of ubiquitin ions formed either directly by electrospray ionization or through collapse of more extended states upon charge reduction, span a similar range of collision cross-sections. Products of gas-phase collapse are, however, less stabilized towards unfolding than the native conformation, indicating that the ions retain a memory of previous conformational states. Furthermore, this collapse of charge-reduced ions is promoted if the ions are ‘preheated’ using collisional activation, with possible implications for the kinetics of gas-phase compaction

Nf2/Merlin controls spinal cord neural progenitor function in a Rac1/ErbB2-dependent manner

Objective: Individuals with the neurofibromatosis type 2 (NF2) cancer predisposition syndrome develop spinal cord glial tumors (ependymomas) that likely originate from neural progenitor cells. Whereas many spinal ependymomas exhibit indolent behavior, the only treatment option for clinically symptomatic tumors is surgery. In this regard, medical therapies are unfortunately lacking due to an incomplete understanding of the critical growth control pathways that govern the function of spinal cord (SC) neural progenitor cells (NPCs). Methods: To identify potential therapeutic targets for these tumors, we leveraged primary mouse Nf2-deficient spinal cord neural progenitor cells. Results: We demonstrate that the Nf2 protein, merlin, negatively regulates spinal neural progenitor cell survival and glial differentiation in an ErbB2-dependent manner, and that NF2-associated spinal ependymomas exhibit increased ErbB2 activation. Moreover, we show that Nf2-deficient SC NPC ErbB2 activation results from Rac1-mediated ErbB2 retention at the plasma membrane. Significance: Collectively, these findings establish ErbB2 as a potential rational therapeutic target for NF2-associated spinal ependymoma

Impaired innate interferon induction in severe therapy resistant atopic asthmatic children

Deficient type I interferon-β and type III interferon-λ induction by rhinoviruses has previously been reported in mild/moderate atopic asthmatic adults. No studies have yet investigated if this occurs in severe therapy resistant asthma (STRA). Here, we show that compared with non-allergic healthy control children, bronchial epithelial cells cultured ex vivo from severe therapy resistant atopic asthmatic children have profoundly impaired interferon-β and interferon-λ mRNA and protein in response to rhinovirus (RV) and polyIC stimulation. Severe treatment resistant asthmatics also exhibited increased virus load, which negatively correlated with interferon mRNA levels. Furthermore, uninfected cells from severe therapy resistant asthmatic children showed lower levels of Toll-like receptor-3 mRNA and reduced retinoic acid inducible gene and melanoma differentiation-associated gene 5 mRNA after RV stimulation. These data expand on the original work, suggesting that the innate anti-viral response to RVs is impaired in asthmatic tissues and demonstrate that this is a feature of STRA

Fear expression is suppressed by tyrosine administration

Animal studies have demonstrated that catecholamines regulate several aspects of fear conditioning. In humans, however, pharmacological manipulations of the catecholaminergic system have been scarce, and their primary focus has been to interfering with catecholaminergic activity after fear acquisition or expression had taken place, using L-Dopa, primarily, as catecholaminergic precursor. Here, we sought to determine if putative increases in presynaptic dopamine and norepinephrine by tyrosine administered before conditioning could affect fear expression. Electrodermal activity (EDA) of 46 healthy participants (24 placebo, 22 tyrosine) was measured in a fear instructed task. Results showed that tyrosine abolished fear expression compared to placebo. Importantly, tyrosine did not affect EDA responses to the aversive stimulus (UCS) or alter participants' mood. Therefore, the effect of tyrosine on fear expression cannot be attributed to these factors. Taken together, these findings provide evidence that the catecholaminergic system influences fear expression in humans

Exploring perceptions of advertising ethics: an informant-derived approach

Whilst considerable research exists on determining consumer responses to pre-determined statements within numerous ad ethics contexts, our understanding of consumer thoughts regarding ad ethics in general remains lacking. The purpose of our study therefore is to provide a first illustration of an emic and informant-based derivation of perceived ad ethics. The authors use multi-dimensional scaling as an approach enabling the emic, or locally derived deconstruction of perceived ad ethics. Given recent calls to develop our understanding of ad ethics in different cultural contexts, and in particular within the Middle East and North Africa (MENA) region, we use Lebanon—the most ethically charged advertising environment within MENA—as an illustrative context for our study. Results confirm the multi-faceted and pluralistic nature of ad ethics as comprising a number of dimensional themes already salient in the existing literature but in addition, we also find evidence for a bipolar relationship between individual themes. The specific pattern of inductively derived relationships is culturally bound. Implications of the findings are discussed, followed by limitations of the study and recommendations for further research

Skp is a multivalent chaperone of outer membrane proteins

The trimeric chaperone Skp sequesters outer-membrane proteins (OMPs) within a hydrophobic cage, thereby preventing their aggregation during transport across the periplasm in Gram-negative bacteria. Here, we studied the interaction between Escherichia coli Skp and five OMPs of varying size. Investigations of the kinetics of OMP folding revealed that higher Skp/OMP ratios are required to prevent the folding of 16-stranded OMPs compared with their 8-stranded counterparts. Ion mobility spectrometry–mass spectrometry (IMS–MS) data, computer modeling and molecular dynamics simulations provided evidence that 10- to 16-stranded OMPs are encapsulated within an expanded Skp substrate cage. For OMPs that cannot be fully accommodated in the expanded cavity, sequestration is achieved by binding of an additional Skp trimer. The results suggest a new mechanism for Skp chaperone activity involving the coordination of multiple copies of Skp in protecting a single substrate from aggregation

Full field electroretinogram in autism spectrum disorder

Purpose To explore early findings that individuals with autism spectrum disorder (ASD) have reduced scotopic ERG b-wave amplitudes. Methods Dark adapted (DA) ERGs were acquired to a range of flash strengths, (-4.0 to 2.3 log phot cd.s.m-2), including and extending the ISCEV standard, from two subject groups: (ASD) N=11 and (Control) N=15 for DA and N=14 for light adapted (LA) ERGs who were matched for mean age and range. Naka-Rushton curves were fitted to DA b-wave amplitude growth over the first limb (-4.0 to -1.0 log phot cd.s.m-2). The derived parameters (Vmax, Km and n) were compared between groups. Scotopic 15 Hz flicker ERGs (14.93Hz) were recorded to 10 flash strengths presented in ascending order from -3.0 to 0.5 log Td.s to assess the slow and fast rod pathways respectively. LA ERGs were acquired to a range of flash strengths, (-0.5 to 1.0 log phot cd.s.m-2). Photopic 30 Hz, flicker ERGs, oscillatory potentials (OPs) and the responses to prolonged 120 ms ON- OFF stimuli were also recorded. Results For some individuals the DA b-wave amplitudes fell below the control 5th centile of the controls with up to four ASD participants (36%) at the 1.5 log phot cd.s.m-2 flash strength and two (18%) ASD participants at the lower -2 log phot cd.s.m-2 flash strength. However, across the thirteen flash strengths there were no significant group differences for b-wave amplitude’s growth (repeated measures ANOVA p=0.83). Nor were there any significant differences between the groups for the Naka-Rushton parameters (p>0.09). No group differences were observed in the 15Hz scotopic flicker phase or amplitude (p>0.1), DA ERG a- wave amplitude or time to peak (p>26). The DA b-wave time to peak at 0.5 log phot cd.s.m-2 were longer in the ASD group (corrected p=0.04). The single ISCEV LA 0.5 log phot cd.s.m-2 (p0.08) to the single flash stimuli although there was a significant interaction between group and flash strength for the b-wave amplitude (corrected p=0.006). The prolonged 120 ms ON-responses were smaller in the ASD group (corrected p=0.003), but the OFF response amplitude (p>0.6) and ON and OFF times to peaks (p>0.4) were similar between groups. The LA OPs showed an earlier bifurcation of OP2 in the younger ASD participants, however no other differences were apparent in the OPs or 30Hz flicker waveforms. Conclusion Some ASD individuals show subnormal DA ERG b-wave amplitudes. Under LA conditions the b-wave is reduced across the ASD group along with the ON response of the ERG. These exploratory findings, suggest there is altered cone-ON bipolar signalling in ASD