Equilibrium binding energies from fluctuation theorems and force spectroscopy simulations

Brownian dynamics simulations are used to study the detachment of a particle from a substrate. Although the model is simple and generic, we attempt to map its energy, length and time scales onto a specific experimental system, namely a bead that is weakly bound to a cell and then removed by an optical tweezer. The external driving force arises from the combined optical tweezer and substrate potentials, and thermal fluctuations are taken into account by a Brownian force. The Jarzynski equality and Crooks' fluctuation theorem are applied to obtain the equilibrium free energy difference between the final and initial states. To this end, we sample non--equilibrium work trajectories for various tweezer pulling rates. We argue that this methodology should also be feasible experimentally for the envisioned system. Furthermore, we outline how the measurement of a whole free energy profile would allow the experimentalist to retrieve the unknown substrate potential by means of a suitable deconvolution. The influence of the pulling rate on the accuracy of the results is investigated, and umbrella sampling is used to obtain the equilibrium probability of particle escape for a variety of trap potentials.Comment: 21 pages, 11 figures, To appear in Soft Matte

Creatine supplementation enhances muscle force recovery after eccentrically-induced muscle damage in healthy individuals

Eccentric exercise-induced damage leads to reductions in muscle force, increased soreness, and impaired muscle function. Creatine monohydrate's (Cr) ergogenic potential is well established; however few studies have directly examined the effects of Cr supplementation on recovery after damage. We examined the effects of Cr supplementation on muscle proteins and force recovery after eccentrically-induced muscle damage in healthy individuals. The major finding of this investigation was a significant improvement in the rate of recovery of knee extensor muscle function after Cr supplementation following injury

Whey protein isolate attenuates strength decline after eccentrically-induced muscle damage in healthy individuals

We examined the effects of short-term consumption of whey protein isolate on muscle proteins and force recovery after eccentrically-induced muscle damage in healthy individuals. The major finding of this investigation was that whey protein isolate supplementation attenuated the impairment in isometric and isokinetic muscle forces during recovery from exercise-induced muscle injury

A national survey of clinical practice for the management of whiplash-associated disorders in UK emergency departments

Objective: To undertake a national survey to determine current practice for the management of whiplash injuries in UK emergency departments (ED). Methods: Postal questionnaire survey. 316 lead consultants from all UK ED with annual new attendances of over 50 000 people were asked to indicate the use of a range of treatments and the frequency with which these treatments were used. Samples of written advice were requested and content analysis was conducted and compared with survey responses. Results: The response rate was 79% (251/316). The intervention most frequently used was verbal advice to exercise, reported by 84% of respondents for most or all cases, and advice against the use of a collar (83%). Other treatments reported as being used frequently were written advice and anti-inflammatory medication. 106 consultants (42%) provided a sample of written materials. Reference to expected recovery and encouragement for early return to activities were included in less than 6%. Nearly 50% of written materials contained information on how to use a soft collar and 61% contained information on solicitors and pursuing a personal injury claim. There were important differences between reported verbal behaviours and written advice. Conclusion: Verbal advice is the primary method for managing whiplash injuries in ED and is usually supplemented by written advice. Within individual hospitals there is a lack of consistency between verbal and written advice. The promotion of personal injury claims is a common feature of written advice. Research is required to develop effective and consistent models of advice

Mutation of the Mouse Syce1 Gene Disrupts Synapsis and Suggests a Link between Synaptonemal Complex Structural Components and DNA Repair

In mammals, the synaptonemal complex is a structure required to complete crossover recombination. Although suggested by cytological work, in vivo links between the structural proteins of the synaptonemal complex and the proteins of the recombination process have not previously been made. The central element of the synaptonemal complex is traversed by DNA at sites of recombination and presents a logical place to look for interactions between these components. There are four known central element proteins, three of which have previously been mutated. Here, we complete the set by creating a null mutation in the Syce1 gene in mouse. The resulting disruption of synapsis in these animals has allowed us to demonstrate a biochemical interaction between the structural protein SYCE2 and the repair protein RAD51. In normal meiosis, this interaction may be responsible for promoting homologous synapsis from sites of recombination

Accelerating Bayesian hierarchical clustering of time series data with a randomised algorithm

We live in an era of abundant data. This has necessitated the development of new and innovative statistical algorithms to get the most from experimental data. For example, faster algorithms make practical the analysis of larger genomic data sets, allowing us to extend the utility of cutting-edge statistical methods. We present a randomised algorithm that accelerates the clustering of time series data using the Bayesian Hierarchical Clustering (BHC) statistical method. BHC is a general method for clustering any discretely sampled time series data. In this paper we focus on a particular application to microarray gene expression data. We define and analyse the randomised algorithm, before presenting results on both synthetic and real biological data sets. We show that the randomised algorithm leads to substantial gains in speed with minimal loss in clustering quality. The randomised time series BHC algorithm is available as part of the R package BHC, which is available for download from Bioconductor (version 2.10 and above) via http://bioconductor.org/packages/2.10/bioc/html/BHC.html. We have also made available a set of R scripts which can be used to reproduce the analyses carried out in this paper. These are available from the following URL. https://sites.google.com/site/randomisedbhc/

Where and what you drink is linked to how much you drink: A survey of alcohol use in 17 countries

Background:  This paper aimed to explore the differences in subjective experiences of intoxication depending on drinking location and drink type. Methods: Data came from 32,194 respondents to The Global Drug Survey (GDS) 2015, an annual, cross-sectional, online survey. Respondents selected their usual drinking location (home alone: home with partner/family: house parties: pubs/bars or clubs) and usual drink (wine; beer/cider/lager; spirits or alcopops/coolers). They indicated how many drinks they required to reach three stages of intoxication (feeling the effects; an ideal stage of intoxication; and the tipping point) and how frequently they reached each stage. Results: Drink type affected grams of alcohol reported to reach the tipping point: 109gm wine, 127gm alcopops, 133gm of beer, and 134gm of spirts. Respondents who drank at home alone, or in clubs reached their tipping point more frequently compared to other locations. Conclusions: Where people drink, and the type of alcohol they drink, affected the amount of alcohol reported to reach different stages of intoxication. Understanding why different drinking locations, and drink types lead to a need for greater consumption to reach an ideal state of drunkenness, such as social cues from other people who drink, may enable people to reduce their drinking

Drinking to excess and the tipping point: An international study of alcohol intoxication in 61,000 people

Background: People who drink alcohol often seek to manage their intake in order to maximise the pleasurable effects, such as feelings of sociability and relaxation, without reaching their ‘tipping point’, where they feel out of control, or unwell. This paper aimed to explore three stages of intoxication; feeling the effects; being as drunk as you would like to be; and reaching the tipping point (feeling more drunk than you want to be) in a large international sample. Methods: The Global Drug Survey (GDS) is an annual, cross-sectional, online survey of drug use. This paper draws on data from 61,043 respondents (63.7% male) from 21 countries who took part in GDS2015 collected in November 2014 to January 2015. Respondents reported their usual type of drink; how many drinks they would require to reach each stage of intoxication and how frequently they reached each stage. Alongside socio-demographic measures, they also completed the Alcohol Use Disorders Identification Test (AUDIT). Results: Male respondents reported consuming 87.55gm to be as drunk as they want to be and female respondents reported 70.16gm, on average. The tipping point was reached at 138.65gm for male respondents and 106.54 gm for female respondents. Overall 20.3% reported reaching their tipping point at least once a month. Being male, aged under 25 and at higher risk for alcohol use disorder was associated with reporting reaching the tipping point more frequently. Conclusions: The amount of alcohol being consumed to reach a desired point of intoxication is much higher than the maximum daily, and sometimes weekly, amount recommended by country guidelines. Encouraging people to avoid reaching their tipping point may be a useful intervention point alongside better communication of low risk drinking guidelines