bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of exercise selection on hamstring muscle activation
Authors: Bourne Matthew N , Williams Morgan D , Opar David A , Al Najjar Aiman , Kerr Graham K , Shield Anthony J
Published: May 2016

Objective

To determine which strength training exercises selectively activate the biceps femoris long head (BFLongHead) muscle.

Methods

We recruited 24 recreationally active men for this two-part observational study.Part 1: We explored the amplitudes and the ratios of lateral (BF) to medial hamstring (MH) normalised electromyography (nEMG) during the concentric and eccentric phases of 10 common strength training exercises. Part 2: We used functional MRI (fMRI) to determine the spatial patterns of hamstring activation during two exercises which (1) most selectively and (2) least selectively activated the BF in part 1.

Results

Eccentrically, the largest BF/MH nEMG ratio occurred in the 45° hip-extension exercise; the lowest was in the Nordic hamstring (Nordic) and bent-knee bridge exercises. Concentrically, the highest BF/MH nEMG ratio occurred during the lunge and 45° hip extension; the lowest was during the leg curl and bent-knee bridge. fMRI revealed a greater BF(LongHead)to semitendinosus activation ratio in the 45° hip extension than the Nordic (p<0.001). The T2 increase after hip extension for BFLongHead, semitendinosus and semimembranosus muscles was greater than that for BFShortHead(p<0.001). During the Nordic, the T2 increase was greater for the semitendinosus than for the other hamstring muscles (p≤0.002).

We highlight the heterogeneity of hamstring activation patterns in different tasks. Hip-extension exercise selectively activates the long hamstrings, and the Nordic exercise preferentially recruits the semitendinosus. These findings have implications for strategies to prevent hamstring injury as well as potentially for clinicians targeting specific hamstring components for treatment (mechanotherapy).
Focused ultrasound and metrics of diffusion of disruptive medical innovation
Authors: Pomeraniec I Jonathan , Spekman Robert , Kassell Neal
Published: May 2016

Innovation, as a concept in healthcare, has broad implications ranging from diagnosis to treatment of disease. The advent of new surgical modalities and medical devices continues to refine and reshape the provision of care for millions of patients across the world. Despite the tangible promise of such innovation, there remains a dearth of frameworks to understand how and how much progress has been made, particularly with regard to early-stage, non-invasive therapeutic technologies that have the potential to transform the treatment of medical disorders. A chief example of this is provided by MR-guided Focused Ultrasound. To the best of our knowledge, there are no prior reviews of the factors affecting adoption and diffusion of MR-guided Focused Ultrasound as a proxy for disruptive medical technologies. The purpose of this review is to provide a comprehensive set of metrics to measure the factors affecting the rate of adoption and diffusion of these medical technologies with special focus on MR-guided Focused Ultrasound, Gamma Knife radiosurgery, and the da Vinci system. The authors review background information and literature regarding innovation in medical technology, and what constitutes disruptive innovation in the medical field. Metrics of adoption and diffusion are evaluated and applied to MR-guided Focused Ultrasound. Gamma Knife radiosurgery and the da Vinci system provide reasonable proxy technologies to understand the factors affecting the adoption and diffusion of MR-guided Focused Ultrasound. With a more comprehensive set of metrics to measure the rate of uptake and use of disruptive technology, we might move towards a better understanding of the limitations of new and potentially beneficial therapeutic modalities.
Strengthening leadership as a catalyst for enhanced patient safety culture: a repeated cross-sectional experimental study
Authors: Kristensen Solvejg , Christensen Karl Bang , Jaquet Annette , Møller Beck Carsten , Sabroe Svend , Bartels Paul , Mainz Jan
Published: May 2016

Objectives

Current literature emphasises that clinical leaders are in a position to enable a culture of safety, and that the safety culture is a performance mediator with the potential to influence patient outcomes. This paper aims to investigate staff's perceptions of patient safety culture in a Danish psychiatric department before and after a leadership intervention.

Methods

A repeated cross-sectional experimental study by design was applied. In 2 surveys, healthcare staff were asked about their perceptions of the patient safety culture using the 7 patient safety culture dimensions in the Safety Attitudes Questionnaire. To broaden knowledge and strengthen leadership skills, a multicomponent programme consisting of academic input, exercises, reflections and discussions, networking, and action learning was implemented among the clinical area level leaders.

Results

In total, 358 and 325 staff members participated before and after the intervention, respectively. 19 of the staff members were clinical area level leaders. In both surveys, the response rate was >75%. The proportion of frontline staff with positive attitudes improved by ≥5% for 5 of the 7 patient safety culture dimensions over time. 6 patient safety culture dimensions became more positive (increase in mean) (p<0.05). Frontline staff became more positive on all dimensions except stress recognition (p<0.05). For the leaders, the opposite was the case (p<0.05). Staff leaving the department after the first measurement had rated job satisfaction lower than the staff staying on (p<0.05).

Conclusions

The improvements documented in the patient safety culture are remarkable, and imply that strengthening the leadership can act as a significant catalyst for patient safety culture improvement. Further studies using a longitudinal study design are recommended to investigate the mechanism behind leadership's influence on patient safety culture, sustainability of improvements over time, and the association of change in the patient safety culture measures with change in psychiatric patient safety outcomes.
Prescribed opioids in primary care: cross-sectional and longitudinal analyses of influence of patient and practice characteristics
Authors: Foy Robbie , Leaman Ben , McCrorie Carolyn , Petty Duncan , House Allan , Bennett Michael , Carder Paul , Faulkner Simon , Glidewell Liz , West Robert
Published: May 2016

Objectives

To examine trends in opioid prescribing in primary care, identify patient and general practice characteristics associated with long-term and stronger opioid prescribing, and identify associations with changes in opioid prescribing.

Design

Trend, cross-sectional and longitudinal analyses of routinely recorded patient data.

Setting

111 primary care practices in Leeds and Bradford, UK.

Participants

We observed 471 828 patient-years in which all patients represented had at least 1 opioid prescription between April 2005 and March 2012. A cross-sectional analysis included 99 847 patients prescribed opioids between April 2011 and March 2012. A longitudinal analysis included 49 065 patient-years between April 2008 and March 2012. We excluded patients with cancer or treated for substance misuse.

Main outcome measures

Long-term opioid prescribing (4 or more prescriptions within 12 months), stronger opioid prescribing and stepping up to or down from stronger opioids.

Results

Opioid prescribing in the adult population almost doubled for weaker opioids over 2005–2012 and rose over sixfold for stronger opioids. There was marked variation among general practices in the odds of patients stepping up to stronger opioids compared with those not stepping up (range 0.31–3.36), unexplained by practice-level variables. Stepping up to stronger opioids was most strongly associated with being underweight (adjusted OR 3.26, 1.49 to 7.17), increasing polypharmacy (4.15, 3.26 to 5.29 for 10 or more repeat prescriptions), increasing numbers of primary care appointments (3.04, 2.48 to 3.73 for over 12 appointments in the year) and referrals to specialist pain services (5.17, 4.37 to 6.12). Compared with women under 50 years, men under 50 were less likely to step down once prescribed stronger opioids (0.53, 0.37 to 0.75).

Conclusions

While clinicians should be alert to patients at risk of escalated opioid prescribing, much prescribing variation may be attributable to clinical behaviour. Effective strategies targeting clinicians and patients are needed to curb rising prescribing, especially of stronger opioids.
Exploring the views of GPs, people with dementia and their carers on assistive technology: a qualitative study
Authors: Newton Lisa , Dickinson Claire , Gibson Grant , Brittain Katie , Robinson Louise
Published: May 2016

Objectives

To explore the views and experiences of people with dementia, their family carers and general practitioners (GPs) on their knowledge and experience of accessing information about, and use of, assistive technology (AT) in dementia care.

Design

Qualitative methods with semistructured interviews and thematic analysis.

Participants

56 participants comprising 17 GPs, 13 people with dementia and 26 family carers.

Setting

Community care settings in the North East of England.

Results

4 main themes emerged: awareness and experience of AT; accessing information on AT; roles and responsibilities in the current care system and the future commissioning of AT services. All participants had practical experience of witnessing AT being used in practice. For people with dementia and their families, knowledge was usually gained from personal experience rather than from health and social care professionals. For GPs, knowledge was largely gained through experiential, patient-led learning. All groups acknowledged the important role of the voluntary sector but agreed a need for clear information pathways for AT; such pathways were perceived to be essential to both service providers and service commissioners.

Conclusions

People with dementia and their family carers appear to be mainly responsible for driving a gradual increase in both awareness and the use of AT in dementia care. GPs should be equipped with the relevant knowledge to ensure families living with dementia receive appropriate information and support to enable them to live independently for as long as possible. There is an urgent need to simplify current complex community care pathways; as demonstrated in other chronic health conditions, a single point of access and a named lead professional may improve future care.
Pregnancy outcomes in Lebanese women with multiple sclerosis (the LeMS study): a prospective multicentre study
Authors: Fares Jawad , Nassar Anwar H , Gebeily Souheil , Kobeissy Firas , Fares Youssef
Published: May 2016

Objective

The Lebanese Multiple Sclerosis (LeMS) study aims to assess the influence of pregnancy and delivery on the clinical course of multiple sclerosis (MS) in Lebanese women.

Setting

This prospective multicentre study took place in three MS referral university medical centres in Lebanon.

Participants

Included were 29 women over 18 years who had been diagnosed with MS according to the McDonald criteria, and became pregnant between 1995 and 2015. Participating women should have stopped treatment 3 months before conception and become pregnant after the onset of MS. Women were followed up from 1 year preconceptionally and for 4 years postpartum.

Main outcome measures

The annualised relapse rates per participant during each 3-month period during pregnancy and each year postpartum were compared with the relapse rate during the year before pregnancy using the paired two-tailed t test. p Values <0.05 were considered statistically significant for all analyses (95% CI).

Results

64 full-term pregnancies were recorded. All pregnancies (100%) resulted in live births, with no complications or other diseases. In comparison with the prepregnancy year, in which the mean relapse rate±SE was 0.17±0.07, there was a significant reduction in the relapse rate during pregnancy and in the first year postpartum (p=0.02), but an increase in the rate in the second year postpartum (0.21±0.08). Thereafter, from the third year postpartum through the following fourth year, the annualised relapse rate fell slightly but did not differ from the annualised relapse rate recorded in the prepregnancy year (0.17±0.07).

Conclusions

Pregnancy in Lebanese women with MS does not seem to increase the risk of complications. No relapses were observed during pregnancy and in the first year postpartum; however, relapses rebounded in the second year postpartum, and over the long term, returned to the levels that preceded pregnancy.
Is omission of free text records a possible source of data loss and bias in Clinical Practice Research Datalink studies? A case–control study
Authors: Price Sarah J , Stapley Sal A , Shephard Elizabeth , Barraclough Kevin , Hamilton William T
Published: May 2016

Objectives

To estimate data loss and bias in studies of Clinical Practice Research Datalink (CPRD) data that restrict analyses to Read codes, omitting anything recorded as text.

Design

Matched case–control study.

Setting

Patients contributing data to the CPRD.

Participants

4915 bladder and 3635 pancreatic, cancer cases diagnosed between 1 January 2000 and 31 December 2009, matched on age, sex and general practitioner practice to up to 5 controls (bladder: n=21 718; pancreas: n=16 459). The analysis period was the year before cancer diagnosis.

Primary and secondary outcome measures

Frequency of haematuria, jaundice and abdominal pain, grouped by recording style: Read code or text-only (ie, hidden text). The association between recording style and case–control status (χ2test). For each feature, the odds ratio (OR; conditional logistic regression) and positive predictive value (PPV; Bayes’ theorem) for cancer, before and after addition of hidden text records.

Results

Of the 20 958 total records of the features, 7951 (38%) were recorded in hidden text. Hidden text recording was more strongly associated with controls than with cases for haematuria (140/336=42% vs 556/3147=18%) in bladder cancer (χ2test, p<0.001), and for jaundice (21/31=67% vs 463/1565=30%, p<0.0001) and abdominal pain (323/1126=29% vs 397/1789=22%, p<0.001) in pancreatic cancer. Adding hidden text records corrected PPVs of haematuria for bladder cancer from 4.0% (95% CI 3.5% to 4.6%) to 2.9% (2.6% to 3.2%), and of jaundice for pancreatic cancer from 12.8% (7.3% to 21.6%) to 6.3% (4.5% to 8.7%). Adding hidden text records did not alter the PPV of abdominal pain for bladder (codes: 0.14%, 0.13% to 0.16% vs codes plus hidden text: 0.14%, 0.13% to 0.15%) or pancreatic (0.23%, 0.21% to 0.25% vs 0.21%, 0.20% to 0.22%) cancer.

Conclusions

Omission of text records from CPRD studies introduces bias that inflates outcome measures for recognised alarm symptoms. This potentially reinforces clinicians’ views of the known importance of these symptoms, marginalising the significance of ‘low-risk but not no-risk’ symptoms.
Gender differences in the duration of non-work-related sickness absence episodes due to musculoskeletal disorders
Authors: Arcas M Marta , Delclos George L , Torá-Rocamora Isabel , Martínez José Miguel , Benavides Fernando G
Published: May 2016

Background

There is wide evidence that women present longer duration of sickness absence (SA) than men. Musculoskeletal disorders are influenced by gender due to the sexual division of work.

Methods

354 432 episodes of non-work-related SA due to musculoskeletal disorders, which were registered in Catalonia between 2005 and 2008, were selected. The outcome variable was the duration of SA. Frailty survival models, stratified by sex and adjusted for explanatory variables (age, employment status, case management, economic activity and repeated episode), were fitted to study the association between each variable and the duration of SA, obtaining HRs.

Results

Women presented longer SA episodes than men in all variable categories. A trend from shorter to longer duration of SA with increasing age was observed in men, whereas in women, it had a fluctuating pattern. Analysing most frequent diagnostic subgroups from the sample, only ‘non-specific lumbago’ and ‘sciatic lumbago’ showed these age patterns. Frailty survival models applied to these 2 subgroups confirmed the described age patterns in SA duration.

Conclusions

Women have longer non-work-related SA due to musculoskeletal disorders than men. However, while men have longer absences as their age increases, in women some older groups have shorter absences than younger ones. These findings could be explained by gender differences in the interaction between paid work and family demands. Our results highlight the need for continued research on SA from a gender perspective, in order to improve management of SA in terms of clinical practice and public policies.
Does cessation of community water fluoridation lead to an increase in tooth decay? A systematic review of published studies
Authors: McLaren Lindsay , Singhal Sonica
Published: May 2016

Background

Cessation of community water fluoridation (CWF) appears to be occurring with increasing frequency in some regions. Our objective was to comprehensively review published research on the impact of CWF cessation on dental caries.

Methods

We searched 13 multidisciplinary databases. Results were synthesised qualitatively and quantitatively.

Results

We identified 15 instances of CWF cessation (‘intervention’) in 13 countries, which covered a broad time frame (1956–2003) and diverse geographical and political/economic contexts. Overall, results were mixed, but pointed more to an increase in caries postcessation than otherwise. For example, of the 9 studies with at least moderate methodological quality based on criteria we developed for this review, 5 showed an increase in caries postcessation. 3 studies did not show an increase in caries postcessation; however, important postcessation changes (eg, implementation of alternative fluoride delivery programmes) and/or large-scale social change may have contributed to those effects. Of the 3 study groupings that permitted quantitative synthesis, 2 showed statistically significant mean overall increase in caries postcessation; however, quantitative synthesis results must be interpreted cautiously.

Conclusions

Overall, the published research points more to an increase in dental caries post-CWF cessation than otherwise. However, the literature is highly diverse and variable in methodological quality. To build this literature, it is important to exploit research opportunities presented by CWF cessation. Remaining knowledge gaps include the impact of CWF cessation on the distribution of dental caries (ie, equitable or not) and understanding the decision-making circumstances around CWF cessation.
DFT calculations of the molecular structures and vibrational spectra of dimethylzinc and dimethylcadmium complexes with bidentate nitrogen ligands
Authors: Butler Ian S. , Gilson Denis F.R. , Newbury M. Louisa
Published: May 2016

The structures and vibrational spectra of dimethylzinc and dimethylcadmium complexes with o-phenanthroline (PHEN), 2,2′-bipyridine (BIPY), and tetramethylethylenediamine (TMED) have been calculated by DFT methods. The unexpected deviations in the dihedral angles between the plane of the o-phenanthroline ligand and the planes of the dimethyl-metal groups are due to low wavenumber twisting vibrations and the previously unknown locations of the metal–nitrogen stretching motions have been established. The results indicate that the ligands are not strongly bound, suggesting that the complexes may indeed be useful nontoxic precursors to Me2Zn and Me2Cd for use in the electronics industry.
Variability in the growth rates and foliage δ15N values of black spruce trees across a slope gradient in the Alaskan Interior
Authors: Tanaka-Oda Ayumi , Kenzo Tanaka , Toriyama Jumpei , Matsuura Yojiro
Published: May 2016

Black spruce (Picea mariana (Mill.) B.S.P.) is a dominant species on north-facing slopes located on the permafrost in the Alaskan Interior, where tree growth rates vary significantly across slope gradients. To better understand the effects of nitrogen (N) and mycorrhizal associations on plant growth, we investigated the relationships between tree growth and isotope ratios of nitrogen (δ15N) in foliage and roots, because plant δ15N values reflect tree dependencies on N uptake by mycorrhizae. We established two transects (one along a slope gradient, and a second on a north-to-east axis at a fixed elevation) and four plots on the slope gradient transect. We measured current shoot growth of saplings on transects and aboveground biomass (AGB) in the plots. We collected foliage and fine root samples and measured their δ15N signatures and N concentrations. The AGB and shoot growth varied widely across the gradient: values were higher at high elevations and at the east–northeast aspect. Foliage δ15N values and N concentrations were positively correlated with tree growth, but growth rate was negatively correlated with the dependency on mycorrhizae for N uptake. Thus, black spruce had a reduced dependency on mycorrhizae for N uptake on the upper slope, where conditions were N-rich. On the lower slope, where the soil active layer was shallow, black spruce growth was limited and had an elevated dependency on mycorrhizae for N uptake.
Anaerobic digestion for the stabilization of the organic fraction of municipal solid waste: A review
Authors: Chatterjee Biswabandhu , Mazumder Debabrata
Published: May 2016

Anaerobic digestion (AD) of the organic fraction of municipal solid waste (OFMSW) has gained great interest in the last few decades. Presently, among the various municipal solid waste management (MSWM) techniques, such as sanitary land-filling, aerobic or anaerobic composting, and thermal incineration, AD is being considered as the most techno-economically viable method owing to its many advantages. AD not only serves to efficiently manage and treat an enormous quantity of OFMSW but also acts as a convenient source of non-conventional energy. The methane generated via AD of OFMSW serves as a potent substitute for fossil-based fuels. Given the current global energy crisis, this technology may be a welcome boost to the global energy demand. In this review an attempt has been made to provide a comprehensive understanding of: (i) the origin and scope of AD of OFMSW; (ii) the potential of AD for OFMSW stabilization; (iii) various pilot and bench-scale studies conducted hitherto; (iv) the process design aspects of AD of OFMSW; (v) the potential of energy recovery from AD of OFMSW; and (vi) the past experiences of AD of OFMSW. This review also delves into the critical issues that govern the process of AD in stabilizing OFMSW. In addition, the compatibility of AD for MSWM in the Indian scenario compared to other classical methodologies, such as landfilling, composting, thermal incineration, and pyrolysis or gasification, is highlighted. An overview of the overall future prospect of AD of OFMSW is discussed.
Power counting and Wilsonian renormalization in nuclear effective field theory
Authors: Valderrama Manuel Pavón
Published: May 2016

Effective field theories are the most general tool for the description of low energy phenomena. They are universal and systematic: they can be formulated for any low energy systems we can think of and offer a clear guide on how to calculate predictions with reliable error estimates, a feature that is called power counting. These properties can be easily understood in Wilsonian renormalization, in which effective field theories are the low energy renormalization group evolution of a more fundamental — perhaps unknown or unsolvable — high energy theory. In nuclear physics they provide the possibility of a theoretically sound derivation of nuclear forces without having to solve quantum chromodynamics explicitly. However there is the problem of how to organize calculations within nuclear effective field theory: the traditional knowledge about power counting is perturbative but nuclear physics is not. Yet power counting can be derived in Wilsonian renormalization and there is already a fairly good understanding of how to apply these ideas to non-perturbative phenomena and in particular to nuclear physics. Here we review a few of these ideas, explain power counting in two-nucleon scattering and reactions with external probes and hint at how to extend the present analysis beyond the two-body problem.
Voltage control of ferromagnetic resonance
Authors: Zhou Ziyao , Peng Bin , Zhu Mingmin , Liu Ming
Published: May 2016

Voltage control of magnetism in multiferroics, where the ferromagnetism and ferroelectricity are simultaneously exhibiting, is of great importance to achieve compact, fast and energy efficient voltage controllable magnetic/microwave devices. Particularly, these devices are widely used in radar, aircraft, cell phones and satellites, where volume, response time and energy consumption is critical. Researchers realized electric field tuning of magnetic properties like magnetization, magnetic anisotropy and permeability in varied multiferroic heterostructures such as bulk, thin films and nanostructure by different magnetoelectric (ME) coupling mechanism: strain/stress, interfacial charge, spin–electromagnetic (EM) coupling and exchange coupling, etc. In this review, we focus on voltage control of ferromagnetic resonance (FMR) in multiferroics. ME coupling-induced FMR change is critical in microwave devices, where the electric field tuning of magnetic effective anisotropic field determines the tunability of the performance of microwave devices. Experimentally, FMR measurement technique is also an important method to determine the small effective magnetic field change in small amount of magnetic material precisely due to its high sensitivity and to reveal the deep science of multiferroics, especially, voltage control of magnetism in novel mechanisms like interfacial charge, spin–EM coupling and exchange coupling.
Releasing the sequence stratigraphy paradigm. Overview and perspectives
Authors: Ridente Domenico
Published: May 2016

Sequence stratigraphy arose as a paradigm in stratigraphy after the integration of the descriptive seismic method, introduced by Exxon researchers in the 1970s, with genetic concepts linking seismic attributes to sedimentary dynamics. Since then, the sequence stratigraphy model underwent significant modification owing to the increasing scenarios of application, each with its own practical requirements. This led to the fragmentation of the original model into a plethora of sub-methods and the flourishing of redundant notions and terminology. Reviewers striving to preserve the unity and fitness of sequence stratigraphy systematically weakened the central assumption by which it stood as a novelty and a paradigm: the relevance of relative sea-level cycles in shaping strata ‘sequentially’. In contrast to this attitude, the value of a model explicitly relying on the upholding control of sea-level is herein reconsidered, based on the marine record of Quaternary, climate-driven, sea-level cycles. Traditionally conceived as exceptionally short-lived and extraordinary events in the history of the Earth, these cycles are documented worldwide on modern continental margins, providing convincing evidence of how sea-level fluctuations actually shape sequences.
Landslide stability evaluation using high-resolution satellite SAR data in the Three Gorges area
Authors: Shi Xuguo , Liao Mingsheng , Zhang Lu , Balz Timo
Published: May 2016

Because of its centimetre-level precision, SAR interferometry (InSAR) has been widely recognized as an effective tool for large-area deformation mapping. However, applications of InSAR technology are limited by temporal–geometric decorrelation and atmospheric disturbance. Large-field displacement could be underestimated as a result of these limitations. A point-like target offset tracking (PTOT) method that solely uses SAR pixel amplitude information through highly accurate image matching can measure 2D displacements in the azimuth and range directions. This method is minimally affected by decorrelation and weather, and it is more suitable for mapping large displacements. In this study, landslide-prone areas were identified using high-resolution TerraSAR-X InSAR data pairs with short normal baselines and temporal baselines covering Zigui County in the Three Gorges area, and the PTOT method was applied to study potential landslides using image pairs with long temporal baselines. An estimate of the cumulative deformation was given. Time series displacements measured at corner reflectors and point-like targets were analysed. The feasibilities of landslide detection using DInSAR and PTOT methods with high-resolution SAR images were then evaluated and summarized.
Females have greater left ventricular twist mechanics than males during acute reductions to preload
Authors: Williams Alexandra M. , Shave Rob E. , Stembridge Mike , Eves Neil D.
Published: May 2016

Compared to males, females have smaller left ventricular (LV) dimensions and volumes, higher ejection fractions (EF), and higher LV longitudinal and circumferential strain. LV twist mechanics determine ventricular function and are preload-dependent. Therefore, the sex differences in LV structure and myocardial function may result in different mechanics when preload is altered. This study investigated sex differences in LV mechanics during acute challenges to preload. With the use of conventional and speckle-tracking echocardiography, LV structure and function were assessed in 20 males (24 ± 6.2 yr) and 20 females (23 ± 3.1 yr) at baseline and during progressive levels of lower body negative pressure (LBNP). Fourteen participants (8 males, 6 females) were also assessed following a rapid infusion of saline. LV end-diastolic volume, end-systolic volume, stroke volume (SV), and EF were reduced in both groups during LBNP ( P < 0.001). While males had greater absolute volumes ( P < 0.001), there were no sex differences in allometrically scaled volumes at any stage. Sex differences were not detected at baseline in basal rotation, apical rotation, or twist. Apical rotation and twist increased in both groups ( P < 0.001) with LBNP. At −60 mmHg, females had greater apical rotation ( P = 0.009), twist ( P = 0.008), and torsion ( P = 0.002) and faster untwisting velocity ( P = 0.02) than males. There were no differences in mechanics following saline infusion. Females have larger LV twist and a faster untwisting velocity than males during large reductions to preload, supporting that females have a greater reliance on LV twist mechanics to maintain SV during severe reductions to preload.
Differential effects of nebivolol vs. metoprolol on microvascular function in hypertensive humans
Authors: Velasco Alejandro , Solow Elizabeth , Price Angela , Wang Zhongyun , Arbique Debbie , Arbique Gary , Adams-Huet Beverley , Schwedhelm Edzard , Lindner Jonathan R. , Vongpatanasin Wanpen
Published: May 2016

Use of β-adrenergic receptor (AR) blocker is associated with increased risk of fatigue and exercise intolerance. Nebivolol is a newer generation β-blocker, which is thought to avoid this side effect via its vasodilating property. However, the effects of nebivolol on skeletal muscle perfusion during exercise have not been determined in hypertensive patients. Accordingly, we performed contrast-enhanced ultrasound perfusion imaging of the forearm muscles in 25 untreated stage I hypertensive patients at rest and during handgrip exercise at baseline or after 12 wk of treatment with nebivolol (5–20 mg/day) or metoprolol succinate (100–300 mg/day), with a subsequent double crossover for 12 wk. Metoprolol and nebivolol each induced a reduction in the resting blood pressure and heart rate (130.9 ± 2.6/81.7 ± 1.8 vs. 131.6 ± 2.7/80.8 ± 1.5 mmHg and 63 ± 2 vs. 64 ± 2 beats/min) compared with baseline (142.1 ± 2.0/88.7 ± 1.4 mmHg and 75 ± 2 beats/min, respectively, both P < 0.01). Metoprolol significantly attenuated the increase in microvascular blood volume (MBV) during handgrip at 12 and 20 repetitions/min by 50% compared with baseline (mixed-model P < 0.05), which was not observed with nebivolol. Neither metoprolol nor nebivolol affected microvascular flow velocity (MFV). Similarly, metoprolol and nebivolol had no effect on the increase in the conduit brachial artery flow as determined by duplex Doppler ultrasound. Thus our study demonstrated a first direct evidence for metoprolol-induced impairment in the recruitment of microvascular units during exercise in hypertensive humans, which was avoided by nebivolol. This selective reduction in MBV without alteration in MFV by metoprolol suggested impaired vasodilation at the precapillary arteriolar level.
The α11 integrin mediates fibroblast–extracellular matrix–cardiomyocyte interactions in health and disease
Authors: Civitarese Robert A. , Talior-Volodarsky Ilana , Desjardins Jean-Francois , Kabir Golam , Switzer Jennifer , Mitchell Melissa , Kapus Andras , McCulloch Christopher A. , Gullberg Donald , Connelly Kim A.
Published: May 2016

Excessive cardiac interstitial fibrosis impairs normal cardiac function. We have shown that the α11β1 (α11) integrin mediates fibrotic responses to glycated collagen in rat myocardium by a pathway involving transforming growth factor-β. Little is known of the role of the α11 integrin in the developing mammalian heart. Therefore, we examined the impact of deletion of the α11 integrin in wild-type mice and in mice treated with streptozotocin (STZ) to elucidate the role of the α11 integrin in normal cardiac homeostasis and in the pathogenesis of diabetes-related fibrosis. As anticipated, cardiac fibrosis was reduced in α11 integrin knockout mice (α11−/−; C57BL/6 background) treated with STZ compared with STZ-treated wild-type mice ( P < 0.05). Unexpectedly, diastolic function was impaired in both vehicle and STZ-treated α11−/− mice, as shown by the decreased minimum rate of pressure change and prolonged time constant of relaxation in association with increased end-diastolic pressure (all P < 0.05 compared with wild-type mice). Accordingly, we examined the phenotype of untreated α11−/− mice, which demonstrated a reduced cardiomyocyte cross-sectional cell area and myofibril thickness (all P < 0.05 compared with wild-type mice) and impaired myofibril arrangement. Immunostaining for desmin and connexin 43 showed abnormal intermediate filament organization at intercalated disks and impaired gap-junction development. Overall, deletion of the α11 integrin attenuates cardiac fibrosis in the mammalian mouse heart and reduces ECM formation as a result of diabetes. Furthermore, α11 integrin deletion impairs cardiac function and alters cardiomyocyte morphology. These findings shed further light on the poorly understood interaction between the fibroblast–cardiomyocyte and the ECM.
Sarcomere neutralization in inherited cardiomyopathy: small-molecule proof-of-concept to correct hyper-Ca2+-sensitive myofilaments
Authors: Thompson Brian R. , Martindale Joshua , Metzger Joseph M.
Published: May 2016

The sarcomere is the functional unit of the heart. Alterations in sarcomere activation lead to disease states such as hypertrophic and restrictive cardiomyopathy (HCM/RCM). Mutations in many of the sarcomeric genes are causal for HCM/RCM. In most cases, these mutations result in increased Ca2+ sensitivity of the sarcomere, giving rise to altered systolic and diastolic function. There is emerging evidence that small-molecule sarcomere neutralization is a potential therapeutic strategy for HCM/RCM. To pursue proof-of-concept, W7 was used here because of its well-known Ca2+ desensitizer biochemical effects at the level of cardiac troponin C. Acute treatment of adult cardiac myocytes with W7 caused a dose-dependent (1–10 μM) decrease in contractility in a Ca2+-independent manner. Alkalosis was used as an in vitro experimental model of acquired heightened Ca2+ sensitivity, resulting in increased live cell contractility and decreased baseline sarcomere length, which were rapidly corrected with W7. As an inherited cardiomyopathy model, R193H cardiac troponin I (cTnI) transgenic myocytes showed significant decreased baseline sarcomere length and slowed relaxation that were rapidly and dose-dependently corrected by W7. Langendorff whole heart pacing stress showed that R193H cTnI transgenic hearts had elevated end-diastolic pressures at all pacing frequencies compared with hearts from nontransgenic mice. Acute treatment with W7 rapidly restored end-diastolic pressures to normal values in R193H cTnI hearts, supporting a sarcomere intrinsic mechanism of dysfunction. The known off-target effects of W7 notwithstanding, these results provide further proof-of-concept that small-molecule-based sarcomere neutralization is a potential approach to remediate hyper-Ca2+-sensitive sarcomere function.
Adult Patient Care Plan: Management of the Febrile Neutropenic Cancer Patient on an Outpatient Basis
Authors: Rotstein Coleman , Bow Eric J , The Febrile Neutropenia Care Plan Working Group
Published: May 2016

Invasive infection may complicate the course of neutropenic cancer patients receiving intensive chemotherapy. The rate
of complications is related to prognostic factors including the underlying malignant diagnosis, the state of responsiveness
of the underlying disease to treatment, the dose‐intensity of the cytotoxic therapy, the duration of neutropenia, the
performance status of the patient and comorbid conditions. The pathogens involved are usually the patients’ endogenous
microflora, and the sites of infection are those anatomic sites colonized with the endogenous microflora. The approach
to the febrile neutropenic episode requires a sequence of steps including the recognition of the febrile state (oral
temperature higher than 38°C), the depth and duration of the neutropenia (absolute neutrophil count less than
0.5×109/L), the identification of a clinical focus of infection and a potential pathogen, the administration of empirical antibacterial
therapy, and finally, an assessment of the outcome. Management decisions about whether to treat with oral
or parenteral antibacterial agents, with a combination or single agent therapy, or as an inpatient or an outpatient can be
based on an assessments of risks of the severity of the patient’s comorbid conditions and the patient’s risk of developing
medical complications that would require inpatient management. The duration of antimicrobial treatment depends on
the recovery from the state of neutropenia and the origin of the infectious process.
Analysis of Veterinary Drug and Pesticide Residues Using the Ethyl Acetate Multiclass/Multiresidue Method in Milk by Liquid Chromatography-Tandem Mass Spectrometry
Authors: Imamoglu Husniye , Oktem Olgun Elmas
Published: May 2016

A rapid and simple multiclass, ethyl acetate (EtOAc) multiresidue method based on liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) detection was developed for the determination and quantification of 26 veterinary drugs and 187 total pesticide residues in milk. Sample preparation was a simple procedure based on liquid–liquid extraction with ethyl acetate containing 0.1% acetic acid, followed by centrifugation and evaporation of the supernatant. The residue was dissolved in ethyl acetate with 0.1% acetic acid and centrifuged prior to LC-MS/MS analysis. Chromatographic separation of analytes was performed on an Inertsil X-Terra C18 column with acetic acid in methanol and water gradient. The repeatability and reproducibility were in the range of 2 to 13% and 6 to 16%, respectively. The average recoveries ranged from 75 to 120% with the RSD (n=18). The developed method was validated according to the criteria set in Commission Decision 2002/657/EC and SANTE/11945/2015. The validated methodology represents a fast and cheap alternative for the simultaneous analysis of veterinary drug and pesticide residues which can be easily extended to other compounds and matrices.
TheIn VitroLipolysis of Lipid-Based Drug Delivery Systems: A Newly Identified Relationship between Drug Release and Liquid Crystalline Phase
Authors: Xiao Lu , Yi Tao , Liu Ying , Zhou Hua
Published: May 2016

The purpose of this study was to offer a new insight into the microstructure changes duringin vitrolipolysis of five lipid-based drug delivery formulations belonging to different lipid formulation types. Five lipid-based formulations of indomethacin were investigated using anin vitrolipolysis model. During lipolysis, microstructures of the intermediate phase formed by lipolytic products were observed. The results showed that the time of liquid crystal formation duringin vitrodigestion for these formulations was Type I > Type II > Type IIIB > Type IV > Type IIIA (p<0.05). After lipolysis, the drug releases from these formulations were determined. The results showed that the amount of drug distributed in the aqueous phase, obtained by ultracentrifuge after lipolysis, was, astonishingly, in inverse rank order of the above mentioned, that is, Type IIIA > Type IV > Type IIIB > Type II > Type I (p<0.05). These results showed that the liquid crystalline phase probably has a critical influence on the fate of the drug duringin vitrolipolysis and suggested that the liquid crystalline phase facilitated drug precipitation. These findings may improve the understanding of lipolysis of lipid-based drug delivery systems for designing better delivery system.
Metformin Protects H9C2 Cardiomyocytes from High-Glucose and Hypoxia/Reoxygenation Injury via Inhibition of Reactive Oxygen Species Generation and Inflammatory Responses: Role of AMPK and JNK
Authors: Hu Mingyan , Ye Ping , Liao Hua , Chen Manhua , Yang Feiyan
Published: May 2016

Metformin is a first-line drug for the management of type 2 diabetes. Recent studies suggested cardioprotective effects of metformin against ischemia/reperfusion injury. However, it remains elusive whether metformin provides direct protection against hypoxia/reoxygenation (H/R) injury in cardiomyocytes under normal or hyperglycemic conditions. This study in H9C2 rat cardiomyoblasts was designed to determine cell viability under H/R and high-glucose (HG, 33 mM) conditions and the effects of cotreatment with various concentrations of metformin (0, 1, 5, and 10 mM). We further elucidated molecular mechanisms underlying metformin-induced cytoprotection, especially the possible involvement of AMP-activated protein kinase (AMPK) and Jun NH(2)-terminal kinase (JNK). Results indicated that 5 mM metformin improved cell viability, mitochondrial integrity, and respiratory chain activity under HG and/or H/R (P<0.05). The beneficial effects were associated with reduced levels of reactive oxygen species generation and proinflammatory cytokines (TNF-α, IL-1α, and IL-6) (P<0.05). Metformin enhanced phosphorylation level of AMPK and suppressed HG + H/R induced JNK activation. Inhibitor of AMPK (compound C) or activator of JNK (anisomycin) abolished the cytoprotective effects of metformin. In conclusion, our study demonstrated for the first time that metformin possessed direct cytoprotective effects against HG and H/R injury in cardiac cells via signaling mechanisms involving activation of AMPK and concomitant inhibition of JNK.
Effectiveness of Strengthening Exercises for the Elderly with Low Back Pain to Improve Symptoms and Functions: A Systematic Review
Authors: Ishak Nor Azizah , Zahari Zarina , Justine Maria
Published: May 2016

Objective. To determine the effect of strengthening exercises for older people with low back pain (LBP).Methods. This study is a systematic review of experimental study which evaluated the evidence regarding exercises for older people with LBP by using EBSCO Academic Search Premier, EBSCO EconLit, Science Direct, PUBMED, and PEDro from 2006 to 2016. Search strategy for each database was conducted by using keywords such as “low back pain”, “older people”, and “strengthening exercise”. Boolean operators were used to combine keywords and manual exclusion was conducted to verify studies which met the inclusion criteria. The articles reviewed were evaluated and critically appraised by using PEDro scale and SPSS version 20 was used to analyze the data.Results. Three articles were found regarding strengthening exercise for older people with LBP whereas one study was conducted on multicomponent exercise. The mean, standard deviation, and variance of the PEDro score of all the studies were 5.67, 2.33, and 1.528, respectively. Overall, the qualities of all studies reviewed were fair. Two articles showed significant results when compared to control group (p<0.05).Conclusions. Strengthening exercise is a beneficial treatment for older people with LBP in reducing pain intensity, disability, and improved functional performances.
Transit-Based Emergency Evacuation with Transit Signal Priority in Sudden-Onset Disaster
Authors: Lin Ciyun , Gong Bowen
Published: May 2016

This study presents methods of transit signal priority without transit-only lanes for a transit-based emergency evacuation in a sudden-onset disaster. Arterial priority signal coordination is optimized when a traffic signal control system provides priority signals for transit vehicles along an evacuation route. Transit signal priority is determined by “transit vehicle arrival time estimation,” “queuing vehicle dissipation time estimation,” “traffic signal status estimation,” “transit signal optimization,” and “arterial traffic signal coordination for transit vehicle in evacuation route.” It takes advantage of the large capacities of transit vehicles, reduces the evacuation time, and evacuates as many evacuees as possible. The proposed methods were tested on a simulation platform with Paramics V6.0. To evaluate and compare the performance of transit signal priority, three scenarios were simulated in the simulator. The results indicate that the methods of this study can reduce the travel times of transit vehicles along an evacuation route by 13% and 10%, improve the standard deviation of travel time by 16% and 46%, and decrease the average person delay at a signalized intersection by 22% and 17% when the traffic flow saturation along an evacuation route is0.81.0, respectively.
KCl-Dependent Release of Mitochondrial Membrane-Bound Arginase Appears to Be a Novel Variant of Arginase-II
Authors: Suman Mishra , Rajnikant Mishra
Published: May 2016

Arginase regulates arginine metabolism, ornithine-urea cycle, and immunological surveillance. Arginase-I is predominant in cytosol, and arginase-II is localised in the mitochondria. A mitochondrial membrane-bound arginase has also been proposed to be adsorbed with outer membrane of mitochondria which gets released by 150 mM potassium chloride (KCl). It is presumed that inclusion of 150 mM KCl in the homogenization medium would not only facilitate release of arginase bound with outer membrane of mitochondria but also affect functional anatomy of mitochondria, mitochondrial enzymes, and proteins. Therefore, it has been intended to characterize KCl-dependent release of mitochondrial membrane-bound arginase from liver of mice. Results provide advancement in the area of arginase biology and suggest that fraction of mitochondrial membrane-bound arginase contains mitochondrial arginase-II and a variant of arginase-II.
Origin of Serum Affects Quality of Engineered Tissues Produced by the Self-Assembly Approach
Authors: Chabaud Stéphane , Simard Melissa , Gendreau Isabelle , Pouliot Roxane , Bolduc Stéphane
Published: May 2016

Despite the emergence of serum-free media for cell culture, the use of serum to supplement the culture media is still essential in order to produce engineered urologic tissues using the self-assembly approach, not only for the stromal compartment but also for the uroepithelium. Effects of sera on thickness of these two compartments were measured and quality of the epithelial differentiation was evaluated. For bladder mucosa substitute reconstruction, the use of postnatal sera failed to produce an adequate uroepithelium whereas the fetal sera supplementation did. Postnatal sera also provided thinner stromal compartments than the one obtained using fetal sera, no matter if the fibroblasts from healthy or psoriatic donors were used to reconstruct human skin substitutes.