bluuebunny/crossref_metadata_2025 huggingface dataset:
Reflections on work and employment into the 21st century: between equal rights, force decides
Authors: Stuart Mark , Grugulis Irena , Tomlinson Jennifer , Forde Chris , MacKenzie Robert
Published: June 2013

In this introductory article, the editors of Work, Employment and Society reflect on the journal’s body of published work and present the main contributions of the 25-year anniversary issue. As a journal of record WES is now well established and offers extensive conceptual insights into, and empirical analysis of, contemporary trends and experiences of work, employment and unemployment. Yet academic scholarship should also aspire to comment, critique and counter; four themes are elaborated, with reference to the issue’s contributions, to illustrate this: labour market change; work in the service sector; post-Fordism, disconnection and financialization; and moral economy and counter movements.
Synthesis and property of epoxy prepolymer and curing agent with high refractive index
Authors: Luo Chaoyun , Zuo Jiandong , Zhao Jianqing
Published: June 2013

An epoxy prepolymer with high refractive index, diglycidyl ether of thiodiphenol (DGETP), was synthesized by 4,4′-thiodiphenol and epichlorohydrin via a two-step method. The curing agent o-benzenedimethanethiol (OBDMT) was synthesized by thiourea method. Fourier transform infrared spectroscopy and proton nuclear magnetic resonance were employed to characterize the structures of these resins. The cured product of DGETP and OBDMT was analyzed by differential scanning calorimetry, ultraviolet–visible spectrometer, and Abbe refractometer and compared with the property of traditional curing agent of methyl hexahydrophthalic anhydride (MHHPA) and ordinary bisphenol A diglycidyl ether epoxy prepolymer cured products. The lower curing temperature and glass transition temperature of DGETP than those of MHHPA can be mainly attributed to the strong rotation capability of thioether bond. The zero light transmittance region of DGETP/OBDMT curing adhesive (200–380 nm) was broader than that of the other three. The refractive index of DGETP/OBDMT was up to 1.654.
Reliability of a production system with intersectional lines
Authors: Lin Yi-Kuei , Chang Ping-Chen
Published: June 2013

This article addresses reliability evaluation for a production system with intersectional lines and multiple reworking actions, where the reliability is the probability of demand satisfaction. First, the production system is constructed as a capacitated-flow production network by the revised graphical transformation and decomposition techniques. Capacity analysis is implemented to determine the input flow of each workstation subsequently. Second, two algorithms, including a general algorithm, are proposed to generate all minimal capacity vectors that workstations should provide to satisfy demand. The reliability is derived in terms of such vectors accordingly. A real-world case of printed circuit board production system is utilized to demonstrate the performance evaluation procedure.
Lymphogranuloma venereum detected from the pharynx in four London men who have sex with men
Authors: Dosekun O , Edmonds S , Stockwell S , French P , White JA
Published: June 2013

Summary

Lymphogranuloma venereum (LGV) is an established cause of proctitis in men who have sex with men (MSM). Currently in the UK, testing for pharyngeal Chlamydia trachomatis (CT) is not routine, and LGV typing is usually only performed in patients with anorectal symptoms. We report four cases where LGV-associated CT DNA was detected from the pharynx in MSM, demonstrating that nucleic acid amplification testing (NAAT) can be used for detecting and typing pharyngeal CT infection. These cases also highlight other possible routes of infection for LGV, and add to the broad spectrum of clinical presentations associated with this infection.
Liver function test abnormalities in Nigerian patients with human immunodeficiency virus and hepatitis B virus co-infection
Authors: Iroezindu M O , Agbaji O O , Daniyam C A , Isiguzo G C , Isichei C , Akanbi M O
Published: June 2013

Summary

Data on baseline hepatic function of HIV and hepatitis B virus (HBV) co-infected patients are limited in sub-Saharan Africa. We assessed liver function test (LFT) abnormalities in Nigerian patients with HIV/HBV co-infection to highlight the impact of HIV on HBV-related liver disease in sub-Saharan Africa. A cross-sectional study involving 100 HIV/HBV co-infected patients and 100 age- and sex-matched HBV mono-infected controls. Blood testing for HIV antibodies, CD4+ cell count, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), LFTs, platelet count, fasting blood glucose and lipid profile were carried out. Non-invasive hepatic fibrosis scores (aspartate aminotransferase-platelet ratio index [APRI] and FIB-4) were also calculated. Co-infected patients had deranged liver enzymes more than the controls (77% versus 64%, P = 0.04). The predominant patterns of enzyme derangement in co-infected patients were either predominantly ↑ALP (30% versus 4%, P < 0.0001) or mixed (30% versus 15%, P = 0.01) but predominantly ↑AST/ALT in the controls (25% versus 9%, P = 0.003). Co-infected patients had higher fibrosis scores for both APRI ( P = 0.002) and FIB-4 ( P = 0.0001). On further analysis, LFT abnormalities and fibrosis scores were only significantly higher in co-infected patients in the immune clearance and HBeAg-negative chronic hepatitis phases. LFT abnormalities are common in Nigerians with HBV infection and co-infection with HIV negatively impacts on hepatic function.
Rising Stars and Sinking Ships
Authors: Pettit Nathan C. , Sivanathan Niro , Gladstone Eric , Marr Jennifer Carson
Published: June 2013

Differences in rank are a ubiquitous feature of social life. Moving beyond the traditional static view of social hierarchy, five studies spanning multiple contexts examined how intertemporal changes in rank influenced people’s status judgments. When final rank was held constant, people, products, and institutions were judged as higher status when they had arrived at this position by ascending, rather than descending, the hierarchy; moreover, these judgments affected downstream pricing recommendations, willingness to pay for products, and influence accepted from others. This impact of rank history on status judgments was accounted for by expectations of future status and moderated by the involvement of the self: The self and others are afforded an equivalent status boost for ascending to a given rank; however, only the self is pardoned the status tax that is levied on others for descending to the same rank. The theoretical utility of a dynamic approach to social hierarchy is discussed.
Diet Pills, Powders, and Liquids
Authors: Thorlton Janet , Park Chang , Hughes Tonda
Published: June 2013

About 35% of healthy weight adolescent females describe themselves as overweight, and 66% report planning to lose weight. Body weight dissatisfaction is associated with unhealthy weight loss practices including diet pill/powder/liquid (PPL) use. Few studies have examined diet PPL use in healthy weight adolescent females; therefore, Youth Risk Behavior Survey data ( n = 247) were analyzed to identify predictors of use. Descriptive statistics and logistic regression analyses were conducted using Statistical Package for the Social Sciences Complex Samples software. Social cognitive theory served as the framework guiding the analysis. Approximately 8% of healthy weight females reported using diet PPL for weight loss. Describing self as overweight, planning to lose weight, being offered drugs at school, fasting to lose weight, cigarette/alcohol use, vomiting, and laxative use were significantly associated ( p < .05) with diet PPL use. Health professionals, including school nurses, must assess for unhealthy weight loss practices in healthy weight females, in order to adequately address related issues.
Induced Pluripotent Stem Cells and Disorders of the Nervous System
Authors: Faiz Maryam , Nagy Andras
Published: June 2013

Advances in cellular reprograming have shown that the delivery of specific transcription factors can result in the shift of one cell type to another. Brief forced expression of the four Yamanaka reprogramming factors (Klf4, Sox2, c-Myc, and Oct4) is able to convert many cell types into induced pluripotent stem cells, whereas some lineage specific transcription factors can convert cells from one type directly to another. Numerous strategies have already been developed for deriving neural cell types, with the hopes of better understanding/alleviating neurodegenerative disease. These cells facilitate drug discovery and constitute an autologous source of cells for brain repair, thus, avoiding rejection issues faced by allografts derived from embryonic stem cells. However, proper characterization of the various types of reprogrammed cells and an understanding of how these cells acquire neural fate is necessary before their translation into the clinic. Here, we review the progress, problems, and prospects with reprogrammed cell types with regards to neurodegenerative disease.
Acoustic radiation and active control from a smart functionally graded submerged hollow cylinder
Authors: Hasheminejad Seyyed M , Alaei-Varnosfaderani Mahdi
Published: June 2013

The 3D piezoelasticity theory and the spatial state-space approach are used to study the steady-state non-axisymmetric sound radiation and scattering characteristics of an infinitely long, arbitrarily thick, orthotropic functionally graded hollow circular cylinder, coupled with an inner (actuator) layer of functionally graded piezoceramic material. The method of stationary phase is employed for evaluation of the radiated far-field pressure integral. Numerical simulations include water-submerged air-filled steel-PZT4 composite cylinders driven by harmonic electromechanical loads or insonified by an obliquely incident plane sound wave. Also, when the actuator layer is operating in the active vibration mode, the effects of the number of control modes on the input voltage required for partial or complete cancellation of the far-field and internal radiated pressures as well as on the backscattering form function and noise reduction amplitudes are examined. Limiting cases are considered and validity of formulation is established by comparison with available data as well as with the aid of a commercial finite element package.
Steady-state dynamic behavior of an on-board rotor under combined base motions
Authors: Dakel Mzaki , Baguet Sébastien , Dufour Régis
Published: June 2013

In the transportation domain, on-board rotors in bending are subjected not only to rotating mass unbalance but also to several movements of their base. The main objective of this article is to predict the dynamic behavior of a rotor in the presence of base excitations. The proposed on-board rotor model is based on the Timoshenko beam finite element. It takes into account the effects corresponding to rotary inertia, gyroscopic inertia, and shear deformation of shaft as well as the geometric asymmetry of disk and/or shaft and considers six types of deterministic motions (rotations and translations) of the rotor’s rigid base. The use of Lagrange’s equations associated with the finite element method yields the linear second-order differential equations of vibratory motion of the rotating rotor in bending relative to the moving rigid base which forms a non-inertial frame of reference. The linear equations of motion highlight periodic parametric terms due to the geometric asymmetry of the rotor components and time-varying parametric terms due to the rotational motions of the rotor rigid base. These parametric terms are considered as sources of internal excitation and can lead to lateral dynamic instability. In the presented applications, the rotor is excited by a rotating mass unbalance combined with constant rotation and sinusoidal translation of the base. Quasi-analytical and numerical solutions for two different rotor configurations (symmetric and asymmetric) are analyzed by means of stability charts, Campbell diagrams, steady-state responses as well as orbits of the rotor.
Data-filtering-based iterative identification methods for nonlinear FIR-MA systems
Authors: Wang Ziyun , Ji Zhicheng
Published: June 2013

This paper considers identification problems of Hammerstein finite impulse response moving average (FIR-MA) systems and presents a gradient-based iterative algorithm and a least-squares-based iterative algorithm to estimate the parameters of the Hammerstein systems by using the data filtering technique. The analysis and simulation results show that the gradient-based iterative algorithm has a higher computational efficiency than the least-squares-based iterative algorithm.
On the analytical and experimental assessment of the performance of a quasi-zero-stiffness isolator
Authors: Xu Daolin , Zhang Yueying , Zhou Jiaxi , Lou Jingjun
Published: June 2013

This paper presents a study of a quasi-zero-stiffness (QZS) isolator. A unique relationship between the geometry configuration and the stiffness of the spring elements is obtained in order to design the property of high-static-low-dynamic stiffness. Analytical solutions of the nonlinear QZS system are derived with the harmonic balance method for the characteristic analysis of the force transmissibility and critical conditions for occurring jump-down and jump-up phenomena. The effects of damping and excitation force on the system behaviors are discussed. A series of experimental tests demonstrate that the QZS system greatly outperforms a corresponding linear isolation system. The former enables vibration to be attenuated at 0.5 Hz, while the latter can only execute attenuation after 4.2 Hz. The QZS system is especially effective for vibration isolation in the low-frequency range.
The Relevance of Cultural Tourism as the Next Frontier for Small Island Destinations
Authors: Croes Robertico , Semrad Kelly J.
Published: June 2013

The purpose of this study is to apply the cultural tourism typology of McKercher and to estimate the economic relevance of cultural tourism to the context of a small island destination tourist market. Small island destinations may be confronted with environmental constraints that restrain the traditional small island tourism development model, which is based on sun, sand, and sea. The cultural tourism typology is used in order to determine whether the typology may be used to segment tourists thereby allowing researchers to determine the economic impact of different cultural tourist segments. This study draws attention to some of the foundational issues that researchers face when attempting to quantify the economic impact of cultural tourists. The results of the study indicate that McKercher’s typology may provide more refined results when incorporating the purpose of a trip; and, that cultural tourists may be a lucrative market for destinations to pursue given the results of an economic input–output model.
The Impact of Servicescape Cues on Consumer Prepurchase Authenticity Assessment and Patronage Intentions to Ethnic Restaurants
Authors: Wang Chen-Ya , Mattila Anna S.
Published: June 2013

In the context of ethnic dining services, authenticity is the key ingredient. This study aims to investigate the impact of servicescape dimensions on consumers’ prepurchase authenticity perceptions and patronage intentions to ethnic restaurants. The authors propose that three key dimensions of the servicescape—the physical setting, service providers, and other customers—provide ethnic-associated cues for consumers to assess authenticity in the preconsumption stage. Empirical results from a between-subject experimental design suggest that servicescape dimensions can induce preconsumption authenticity perceptions of ethnic restaurants and that the dimensional cues interplay to affect authenticity assessments. Furthermore, a customer’s ethnicity (referent ethnic vs. mainstream) affects how she/he interprets servicescape cues and, therefore, his/her authenticity assessment. The perceived authenticity, together with a consumer’s trait of cosmopolitanism and his/her familiarity with such ethnic restaurants, consequently affect consumers’ patronage intentions. These findings contribute to hospitality research on consumers’ authenticity assessments of ethnic restaurants. Furthermore, managerial implications for ethnic restaurants in terms of marketing strategies will be discussed.
Sport, glocalization and the new Indian middle class
Authors: Andrews David L. , Batts Callie , Silk Michael
Published: June 2013

Focusing on the structure and influence of transnational sport – namely the Commonwealth Games and fitness culture within the context of contemporary India – we draw on observations derived from empirical research to explore the complex interrelationships between economic liberalization, globalization, and consumer capitalism. Our argument centres on the processes through which contemporary Indian sport culture is being re-made within the image of India’s new middle class; a set of processes that simultaneously contributes toward the hegemony of India’s protuberant new middle class and thereby patently re-inscribes the social inequities and polarities evident within Indian life more generally. Through a contextual consideration of the economic liberalization policies and allied neoliberal ideologies that propelled the emergence of the new middle class (Antonio, 2007), and the consumer culture through which its identities are substantiated and boundaries demarcated (Bauman, 2001), we point to those bodies valorized (productive, consumptive and functional) and those pathologized (impoverished, underserved and disposable) within a transnational sporting culture that espouses the dictates of neoliberal polity, policy and body politics.
Soldiers, scapegoats, and the tragic demands of Operation First Casualty
Authors: Ajello Linell
Published: June 2013

In 2008, the activist group Iraq Veterans Against the War (IVAW) produced Operation First Casualty, a piece of guerrilla theater staged on streets and in parks in U.S. cities, in which members performed actions that they had carried out as they patrolled Iraq and Afghanistan. In opposition to representations of war that excerpt violent events from daily life, IVAW portrays military culture as one of habitual brutality. At the same time, Operation First Casualty placed an audience of American bystanders in positions akin to those of Iraqis and Afghanis, in an attempt to engage empathy for, and enable solidarity with, the people whose countries are occupied by the US. Due to what I describe as soldiers’ function as a scapegoat figure in the national imaginary, IVAW’s insight has had little influence on public discourse. To understand the co-determinacy of the marginal status of soldiers and the social framing that gives the soldier figure such pull, I overlay theories of tragedy and political sociology in which scholars explore the ritualistic dynamics of scapegoats, collective identity, and outsiders in democratic society.
Smooth Pursuit Eye Movement Training Promotes Recovery From Auditory and Visual Neglect
Authors: Kerkhoff Georg , Reinhart Stefan , Ziegler Wolfram , Artinger Frank , Marquardt Christian , Keller Ingo
Published: June 2013

Background. No treatment for auditory neglect and no randomized controlled trial evaluating smooth pursuit eye movement therapy (SPT) for multimodal neglect are available. Objective. To compare the effects of SPT and visual scanning therapy (VST) on auditory and visual neglect in chronic stroke patients with neglect. Methods. A randomized, prospective trial was conducted. Fifty patients with left auditory and visual neglect were randomly assigned. Twenty-four patients completed SPT therapy and 21 patients VST. Five patients (4 VST, 1 SPT) were lost. Each group received 1-hour sessions of neglect therapy for 5 consecutive days totaling 5 hours. Outcome measures in visual neglect (digit cancellation, visuoperceptual- and motor line bisection, paragraph reading) and auditory neglect (auditory midline) were assessed twice before therapy, thereafter, and at 2-week follow-up. The SPT group practiced smooth pursuit eye movements while tracking stimuli moving leftward. The VST group systematically scanned the same but static stimuli. Both groups were divided into subgroups, and effects were separately investigated for mild and severe neglect. Results. Both groups did not differ before therapy in clinical/demographic variables or neglect severity (auditory/visual). After treatment, the SPT group showed significant and lasting improvements in all visual measures and normal performance in the auditory midline. Neither visual nor auditory neglect impairments changed significantly after VST. Moreover, the treatment effect sizes (Cohen’s d) were considerably higher for visual and auditory neglect after SPT versus VST, both for mild and severe neglect. Conclusions. Repetitive contralesional, smooth pursuit training induces superior, multimodal therapeutic effects in mild and severe neglect.
Platelet-Rich Plasma in Addition to Rehabilitation for Acute Hamstring Injuries in NFL Players
Authors: Rettig Arthur C. , Meyer Susan , Bhadra Arup K.
Published: June 2013

Background:

Platelet-rich plasma (PRP) injections have been proposed to hasten soft tissue healing. There is a lack of evidence in the current literature to support their efficacy in elite athletes.

Purpose:

To investigate the effects of the addition of PRP to rehabilitation in the treatment of acute hamstring injuries in professional National Football League (NFL) players and to report the time to return to play.

Study Design:

Case control study.

Methods:

Ten NFL players with similar hamstring injury patterns were retrospectively divided into 2 groups. The treatment group (PRP; n = 5) was injected with PRP and the control group (non-PRP; n = 5) was not injected; both groups completed a rehabilitation program. The PRP injections were administered under ultrasound guidance with precise localization of the injury site, within 24 to 48 hours of injury. Age, muscle involved, extent of injury, grading, and time to return to play were noted. Descriptive statistics and the exact Wilcoxon rank-sum test were used for data analysis.

Results:

The mean age was 23 years (range, 22-27 years) for the PRP group and 26 years (range, 22-28 years) for the non-PRP group ( P = .42). The median longitudinal extent of the injury was 14 cm (range, 9-18 cm) in the PRP group and 15 cm (range, 9-16 cm) in the non-PRP group ( P = .77). The average transverse extent of the injury in the PRP and non-PRP groups was 4 cm (range, 1.6-6 cm) and 3.5 cm (range, 2-5 cm), respectively, and the respective average anteroposterior extent was 4 cm (range, 1.9-5 cm) and 2.9 cm (range, 1.5-4 cm). The long head of biceps femoris was most commonly involved (4 in each group), with a single tear of the semimembranosus in each group. The median injury classification was grade 2 in both groups. The median time to return to play was 20 days (range,16-30 days) in the PRP group and 17 days (range, 8-81 days) in the non-PRP group ( P = .73).

Conclusion:

There were no significant differences in recovery from hamstring injury between treatment with PRP and routine rehabilitation. A larger, randomized controlled trial is warranted.
CC chemokine receptor 8 potentiates donor Treg survival and is critical for the prevention of murine graft-versus-host disease
Authors: Coghill James M. , Fowler Kenneth A. , West Michelle L. , Fulton LeShara M. , van Deventer Hendrik , McKinnon Karen P. , Vincent Benjamin G. , Lin Kaifeng , Panoskaltsis-Mortari Angela , Cook Donald N. , Blazar Bruce R. , Serody Jonathan S.
Published: June 2013

Key Points

Extended donor Treg survival is required for protection from GVHD; donor Treg longevity depends on Treg CCR8 expression. Donor CD11c+ APCs promote Treg longevity in vivo; host CD11c+ APCs do not appear to contribute to donor Treg reconstitution.
Advanced drug delivery systems for antithrombotic agents
Authors: Greineder Colin F. , Howard Melissa D. , Carnemolla Ronald , Cines Douglas B. , Muzykantov Vladimir R.
Published: June 2013

Despite continued achievements in antithrombotic pharmacotherapy, difficulties remain in managing patients at high risk for both thrombosis and hemorrhage. Utility of antithrombotic agents (ATAs) in these settings is restricted by inadequate pharmacokinetics and narrow therapeutic indices. Use of advanced drug delivery systems (ADDSs) may help to circumvent these problems. Various nanocarriers, affinity ligands, and polymer coatings provide ADDSs that have the potential to help optimize ATA pharmacokinetics, target drug delivery to sites of thrombosis, and sense pathologic changes in the vascular microenvironment, such as altered hemodynamic forces, expression of inflammatory markers, and structural differences between mature hemostatic and growing pathological clots. Delivery of ATAs using biomimetic synthetic carriers, host blood cells, and recombinant fusion proteins that are activated preferentially at sites of thrombus development has shown promising outcomes in preclinical models. Further development and translation of ADDSs that spare hemostatic fibrin clots hold promise for extending the utility of ATAs in the management of acute thrombotic disorders through rapid, transient, and targeted thromboprophylaxis. If the potential benefit of this technology is to be realized, a systematic and concerted effort is required to develop clinical trials and translate the use of ADDSs to the clinical arena.
Lenalidomide induces long-lasting responses in elderly patients with chronic lymphocytic leukemia
Authors: Strati Paolo , Keating Michael J. , Wierda William G. , Badoux Xavier C. , Calin Steliana , Reuben James M. , O’Brien Susan , Kornblau Steven M. , Kantarjian Hagop M. , Gao Hui , Ferrajoli Alessandra
Published: June 2013

Key Points

Treatment with lenalidomide induces long-lasting responses. Lenalidomide can produce a sustained increase in immunoglobulin levels and a sustained normalization in circulating T cells.
Automatic workflow for the classification of local DNA conformations
Authors: Čech Petr , Kukal Jaromír , Černý Jiří , Schneider Bohdan , Svozil Daniel
Published: June 2013

Background

A growing number of crystal and NMR structures reveals a considerable structural polymorphism of DNA architecture going well beyond the usual image of a double helical molecule. DNA is highly variable with dinucleotide steps exhibiting a substantial flexibility in a sequence-dependent manner. An analysis of the conformational space of the DNA backbone and the enhancement of our understanding of the conformational dependencies in DNA are therefore important for full comprehension of DNA structural polymorphism.

Results

A detailed classification of local DNA conformations based on the technique of Fourier averaging was published in our previous work. However, this procedure requires a considerable amount of manual work. To overcome this limitation we developed an automatic classification method consisting of the combination of supervised and unsupervised approaches. A proposed workflow is composed of k-NN method followed by a non-hierarchical single-pass clustering algorithm. We applied this workflow to analyze 816 X-ray and 664 NMR DNA structures released till February 2013. We identified and annotated six new conformers, and we assigned four of these conformers to two structurally important DNA families: guanine quadruplexes and Holliday (four-way) junctions. We also compared populations of the assigned conformers in the dataset of X-ray and NMR structures.

Conclusions

In the present work we developed a machine learning workflow for the automatic classification of dinucleotide conformations. Dinucleotides with unassigned conformations can be either classified into one of already known 24 classes or they can be flagged as unclassifiable. The proposed machine learning workflow permits identification of new classes among so far unclassifiable data, and we identified and annotated six new conformations in the X-ray structures released since our previous analysis. The results illustrate the utility of machine learning approaches in the classification of local DNA conformations.
Changing practice as a quality indicator for primary care: analysis of data on voluntary disenrollment from the English GP Patient Survey
Authors: Nagraj Shobhana , Abel Gary , Paddison Charlotte , Payne Rupert , Elliott Marc , Campbell John , Roland Martin
Published: June 2013

Background

Changing family practice (voluntary disenrollment) without changing address may indicate dissatisfaction with care. We investigate the potential to use voluntary disenrollment as a quality indicator for primary care.

Methods

Data from the English national GP Patient Survey (2,169,718 respondents), the number of voluntary disenrollments without change of address, data relating to practice characteristics (ethnicity, deprivation, gender of patients, practice size and practice density) and doctor characteristics were obtained for all family practices in England (n = 8450). Poisson regression analyses examined associations between rates of voluntary disenrollment, patient experience, and practice and doctor characteristics.

Results

Mean and median rates of annual voluntary disenrollment were 11.2 and 7.3 per 1000 patients respectively. Strongest associations with high rates of disenrollment were low practice scores for doctor-patient communication and confidence and trust in the doctor (rate ratios 4.63 and 4.85). In a fully adjusted model, overall satisfaction encompassed other measures of patient experience (rate ratio 3.46). Patients were more likely to move from small practices (single-handed doctors had 2.75 times the disenrollment rate of practices with 6–9 doctors) and where there were other local practices. After allowing for these, substantial unexplained variation remained in practice rates of voluntary disenrollment.

Conclusion

Family practices with low levels of patient satisfaction, especially for doctor patient communication, are more likely to experience high rates of disenrollment. However substantial variation in disenrollment rates remains among practices with similar levels of patient satisfaction, limiting the utility of voluntary disenrollment as a performance indicator for primary care in England.
Macromolecular juggling by ubiquitylation enzymes
Authors: Lorenz Sonja , Cantor Aaron J , Rape Michael , Kuriyan John
Published: June 2013

The posttranslational modification of target proteins with ubiquitin and ubiquitin-like proteins is accomplished by the sequential action of E1, E2, and E3 enzymes. Members of the E1 and E3 enzyme families can undergo particularly large conformational changes during their catalytic cycles, involving the remodeling of domain interfaces. This enables the efficient, directed and regulated handover of ubiquitin from one carrier to the next one. We review some of these conformational transformations, as revealed by crystallographic studies.
Comparing influenza vaccine efficacy against mismatched and matched strains: a systematic review and meta-analysis
Authors: Tricco Andrea C , Chit Ayman , Soobiah Charlene , Hallett David , Meier Genevieve , Chen Maggie H , Tashkandi Mariam , Bauch Chris T , Loeb Mark
Published: June 2013

Background

Influenza vaccines are most effective when the antigens in the vaccine match those of circulating strains. However, antigens contained in the vaccines do not always match circulating strains. In the present work we aimed to examine the vaccine efficacy (VE) afforded by influenza vaccines when they are not well matched to circulating strains.

Methods

We identified randomized clinical trials (RCTs) through MEDLINE, EMBASE, the Cochrane Library, and references of included RCTs. RCTs reporting laboratory-confirmed influenza among healthy participants vaccinated with antigens of matching and non-matching influenza strains were included. Two independent reviewers screened citations/full-text articles, abstracted data, and appraised risk of bias. Conflicts were resolved by discussion. A random effects meta-analysis was conducted. VE was calculated using the following formula: (1 - relative risk × 100%).

Results

We included 34 RCTs, providing data on 47 influenza seasons and 94,821 participants. The live-attenuated influenza vaccine (LAIV) showed significant protection against mismatched (six RCTs, VE 54%, 95% confidence interval (CI) 28% to 71%) and matched (seven RCTs, VE 83%, 95% CI 75% to 88%) influenza strains among children aged 6 to 36 months. Differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 75%, 95% CI 41% to 90%) and mismatched influenza B (five RCTs, VE 42%, 95% CI 22% to 56%) estimates among children aged 6 to 36 months. The trivalent inactivated vaccine (TIV) also afforded significant protection against mismatched (nine RCTs, VE 52%, 95% CI 37% to 63%) and matched (eight RCTs, VE 65%, 95% CI 54% to 73%) influenza strains among adults. Numerical differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 64%, 95% CI 23% to 82%) and mismatched influenza B (eight RCTs, VE 52%, 95% CI 19% to 72%) estimates among adults. Statistical heterogeneity was low (I2 <50%) across all meta-analyses, except for the LAIV meta-analyses among children (I2 = 79%).

Conclusions

The TIV and LAIV vaccines can provide cross protection against non-matching circulating strains. The point estimates for VE were different for matching versus non-matching strains, with overlapping CIs.
Body mass index in relation to truncal asymmetry of healthy adolescents, a physiopathogenetic concept in common with idiopathic scoliosis: summary of an electronic focus group debate of the IBSE
Authors: Grivas Theodoros B , Burwell R Geoffrey , Dangerfield Peter H
Published: June 2013

There is no generally accepted scientific theory for the cause of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE).introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The text for this debate was written by Dr TB Grivas. It is based on published research from Athens, Greece evaluating schoolchildren age 11–17 years for the relation of body mass index (BMI) to each of truncal asymmetry (TA) and menarcheal status. Girls with relatively lower BMI were found to have a significant excess of severe TAs and significantly later menarche confirming the well-known relation of BMI to menarche. Together with other evidence linking nutritional status to skeletal growth, the observations suggest energy balance via the hypothalamus is related to trunk asymmetry. As with a recent speculative hypothesis for the pathogenesis of AIS in girls, Grivas et al. suggest that the severe TAs involve a genetically-determined selectively increased sensitivity (up-regulation) of the hypothalamus to circulating leptin with asymmetry as an adverse response to stress (hormesis). The TA is expressed bilaterally via the sympathetic nervous system to produce left-right asymmetry in ribs and/or vertebrae leading to severe TAs when beyond the capacity of postural mechanisms of the somatic nervous system to control the shape distortion in the trunk. This EFG discusses the findings and interpretations of the paper by Grivas and colleagues as research at the borderland between the genesis of TA (physiogenesis) and AIS (pathogenesis). It is suggested that TAs, here regarded in common with AIS, result from the combination of secondary sexual development affecting body composition, adolescent skeletal growth velocity, and an asymmetry process. The possible involvement of epigenetic factors is not considered.
Functional characterisation of the non-essential protein kinases and phosphatases regulating Aspergillus nidulans hydrolytic enzyme production
Authors: Brown Neil Andrew , de Gouvea Paula Fagundes , Krohn Nádia Graciele , Savoldi Marcela , Goldman Gustavo Henrique
Published: June 2013

Background

Despite recent advances in the understanding of lignocellulolytic enzyme regulation, less is known about how different carbon sources are sensed and the signaling cascades that result in the adaptation of cellular metabolism and hydrolase secretion. Therefore, the role played by non-essential protein kinases (NPK) and phosphatases (NPP) in the sensing of carbon and/or energetic status was investigated in the model filamentous fungus Aspergillus nidulans.

Results

Eleven NPKs and seven NPPs were identified as being involved in cellulase, and in some cases also hemicellulase, production in A. nidulans. The regulation of CreA-mediated carbon catabolite repression (CCR) in the parental strain was determined by fluorescence microscopy, utilising a CreA::GFP fusion protein. The sensing of phosphorylated glucose, via the RAS signalling pathway induced CreA repression, while carbon starvation resulted in derepression. Growth on cellulose represented carbon starvation and derepressing conditions. The involvement of the identified NPKs in the regulation of cellulose-induced responses and CreA derepression was assessed by genome-wide transcriptomics (GEO accession 47810). CreA::GFP localisation and the restoration of endocellulase activity via the introduction of the ∆creA mutation, was assessed in the NPK-deficient backgrounds. The absence of either the schA or snfA kinase dramatically reduced cellulose-induced transcriptional responses, including the expression of hydrolytic enzymes and transporters. The mechanism by which these two NPKs controlled gene transcription was identified, as the NPK-deficient mutants were not able to unlock CreA-mediated carbon catabolite repression under derepressing conditions, such as carbon starvation or growth on cellulose.

Conclusions

Collectively, this study identified multiple kinases and phosphatases involved in the sensing of carbon and/or energetic status, while demonstrating the overlapping, synergistic roles of schA and snfA in the regulation of CreA derepression and hydrolytic enzyme production in A. nidulans. The importance of a carbon starvation-induced signal for CreA derepression, permitting transcriptional activator binding, appeared paramount for hydrolase secretion.
Chromosomal Abnormalities Are Major Prognostic Factors in Elderly Patients With Multiple Myeloma: The Intergroupe Francophone du Myélome Experience
Authors: Avet-Loiseau Hervé , Hulin Cyrille , Campion Loic , Rodon Philippe , Marit Gerald , Attal Michel , Royer Bruno , Dib Mamoun , Voillat Laurent , Bouscary Didier , Caillot Denis , Wetterwald Marc , Pegourie Brigitte , Lepeu Gerard , Corront Bernadette , Karlin Lionel , Stoppa Anne-Marie , Fuzibet Jean-Gabriel , Delbrel Xavier , Guilhot Francois , Kolb Brigitte , Decaux Olivier , Lamy Thierry , Garderet Laurent , Allangba Olivier , Lifermann Francois , Anglaret Bruno , Moreau Philippe , Harousseau Jean-Luc , Facon Thierry
Published: June 2013

Purpose

Chromosomal abnormalities, especially t(4;14) and del(17p), are major prognostic factors in patients with multiple myeloma (MM). However, this has been especially demonstrated in patients age < 66 years treated with intensive approaches. The goal of this study was to address this issue in elderly patients treated with conventional-dose chemotherapy.

Patients and Methods

To answer this important question, we retrospectively analyzed a series of 1,890 patients (median age, 72 years; range, 66 to 94 years), including 1,095 with updated data on treatment modalities and survival.

Results

This large study first showed that the incidence of t(4;14) was not uniform over age, with a marked decrease in the oldest patients. Second, it showed that both t(4;14) and del(17p) retained their prognostic value in elderly patients treated with melphalan and prednisone–based chemotherapy.

Conclusion

t(4;14) and del(17p) are major prognostic factors in elderly patients with MM, both for progression-free and overall survival, indicating that these two abnormalities should be investigated at diagnosis of MM, regardless of age.
Role of Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem-Cell Transplantation in Older Patients With De Novo Myelodysplastic Syndromes: An International Collaborative Decision Analysis
Authors: Koreth John , Pidala Joseph , Perez Waleska S. , Deeg H. Joachim , Garcia-Manero Guillermo , Malcovati Luca , Cazzola Mario , Park Sophie , Itzykson Raphael , Ades Lionel , Fenaux Pierre , Jadersten Martin , Hellstrom-Lindberg Eva , Gale Robert Peter , Beach C.L. , Lee Stephanie J. , Horowitz Mary M. , Greenberg Peter L. , Tallman Martin S. , DiPersio John F. , Bunjes Donald , Weisdorf Daniel J. , Cutler Corey
Published: June 2013

Purpose

Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders that are more common in patients aged ≥ 60 years and are incurable with conventional therapies. Reduced-intensity conditioning (RIC) allogeneic hematopoietic stem-cell transplantation is potentially curative but has additional mortality risk. We evaluated RIC transplantation versus nontransplantation therapies in older patients with MDS stratified by International Prognostic Scoring System (IPSS) risk.

Patients and Methods

A Markov decision model with quality-of-life utility estimates for different MDS and transplantation states was assessed. Outcomes were life expectancy (LE) and quality-adjusted life expectancy (QALE). A total of 514 patients with de novo MDS aged 60 to 70 years were evaluated. Chronic myelomonocytic leukemia, isolated 5q– syndrome, unclassifiable, and therapy-related MDS were excluded. Transplantation using T-cell depletion or HLA-mismatched or umbilical cord donors was also excluded. RIC transplantation (n = 132) stratified by IPSS risk was compared with best supportive care for patients with nonanemic low/intermediate-1 IPSS (n = 123), hematopoietic growth factors for patients with anemic low/intermediate-1 IPSS (n = 94), and hypomethylating agents for patients with intermediate-2/high IPSS (n = 165).

Results

For patients with low/intermediate-1 IPSS MDS, RIC transplantation LE was 38 months versus 77 months with nontransplantation approaches. QALE and sensitivity analysis did not favor RIC transplantation across plausible utility estimates. For intermediate-2/high IPSS MDS, RIC transplantation LE was 36 months versus 28 months for nontransplantation therapies. QALE and sensitivity analysis favored RIC transplantation across plausible utility estimates.

Conclusion

For patients with de novo MDS aged 60 to 70 years, favored treatments vary with IPSS risk. For low/intermediate-1 IPSS, nontransplantation approaches are preferred. For intermediate-2/high IPSS, RIC transplantation offers overall and quality-adjusted survival benefit.
Treatment-Related Mortality in Patients With Advanced-Stage Hodgkin Lymphoma: An Analysis of the German Hodgkin Study Group
Authors: Wongso Diana , Fuchs Michael , Plütschow Annette , Klimm Beate , Sasse Stephanie , Hertenstein Bernd , Maschmeyer Georg , Vieler Tom , Dührsen Ulrich , Lindemann Walter , Aulitzky Walter , Diehl Volker , Borchmann Peter , Engert Andreas
Published: June 2013

Purpose

The introduction of BEACOPPescalated (escalated-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) has significantly improved tumor control and overall survival in patients with advanced-stage Hodgkin lymphoma. However, this regimen has also been associated with higher treatment-related mortality (TRM). Thus, we analyzed clinical course and risk factors associated with TRM during treatment with BEACOPPescalated.

Patients and Methods

In this retrospective analysis, we investigated incidence, clinical features, and risk factors for BEACOPPescalated-associated TRM in the German Hodgkin Study Group trials HD9, HD12, and HD15.

Results

Among a total of 3,402 patients, TRM of 1.9% (64 of 3,402) was mainly related to neutropenic infections (n = 56; 87.5%). Twenty of 64 events occurred during the first course of BEACOPPescalated (31.3%). Higher risk of TRM was seen in patients age ≥ 40 years with poor performance status (PS) and in patients age ≥ 50 years. PS and age were then used to construct a new risk score; those with a score ≥ 2 had TRM of 7.1%, whereas patients who scored 0 or 1 had TRM of 0.9%.

Conclusion

The individual risk of TRM associated with BEACOPPescalated can be predicted by a simple algorithm based on age and PS. High-risk patients should receive special clinical attention.
Central Hypothyroidism and Its Replacement Have a Significant Influence on Cardiovascular Risk Factors in Adult Hypopituitary Patients
Authors: Klose M. , Marina D. , Hartoft-Nielsen M.-L. , Klefter O. , Gavan V. , Hilsted L. , Rasmussen Å. K. , Feldt-Rasmussen U.
Published: June 2013

Context:

Thyroid dysfunction may have detrimental effects on patient outcomes. Few studies have assessed this issue in patients with secondary hypothyroidism.

Objective:

Our objective was to test the hypothesis that thyroid hormone status has an impact on cardiovascular risk factors in adult patients with hypopituitarism.

Design and Setting:

This was a retrospective observational study (1993–2012) at a tertiary referral university hospital.

Patients:

All GH-deficient patients starting GH replacement (1993–2009) with measured free T4 (fT4) (n = 208). Baseline fT4 defined patients as TSH-sufficient and TSH-deficient (further divided into tertiles according to baseline fT4; first tertile had lowest fT4).

Main Outcome Measures:

Anthropometric (body mass index [BMI], waist circumference, total fat (fat mass) and lean body mass [LBM]) and biochemical (lipids and fasting plasma glucose) data were collected at baseline and a median 4.1 years after commencement of GH.

Results:

At baseline, fT4 was negatively associated with BMI and waist circumference, but positively with high-density lipoprotein, independent of age, gender, and IGF-I (SD score). Only first-tertile TSH-deficient patients had higher BMI (P = .02), fat mass (P = .03), total cholesterol (P = .05), triglycerides (P < .01), and waist circumference (P = .01), and lower high-density lipoprotein cholesterol (P = .03) as compared with TSH-sufficient patients. At follow-up, IGF-I, LBM, and plasma glucose had increased in all subgroups (P < .01). The change in fT4 (ΔfT4) (follow-up − baseline) was negatively correlated to ΔBMI, ΔLBM, Δtotal cholesterol, and Δlow-density lipoprotein cholesterol (all P < .05, adjusted for ΔIGF-I and ΔGH and hydrocortisone dose). The negative correlation to Δtotal cholesterol and Δlow-density lipoprotein cholesterol persisted only in first-tertile TSH-deficient patients.

Conclusion:

This single-center study over a 20-year period has strengthened the importance of improved awareness of thyroid status and optimal thyroid replacement of hypopituitary patients to reduce cardiovascular risks in hypopituitary patients.
Olfactory ensheathing glia are required for embryonic olfactory axon targeting and the migration of gonadotropin-releasing hormone neurons
Authors: Barraud Perrine , St John James A. , Stolt C. Claus , Wegner Michael , Baker Clare V. H.
Published: June 2013

Kallmann's syndrome is caused by the failure of olfactory axons and gonadotropin-releasing hormone (GnRH) neurons to enter the embryonic forebrain, resulting in anosmia and sterility. Sox10 mutations have been associated with Kallmann's syndrome phenotypes, but their effect on olfactory system development is unknown. We recently showed that Sox10 is expressed by neural crest-derived olfactory ensheathing cells (OECs). Here, we demonstrate that in homozygous Sox10lacZ/lacZ mouse embryos, OEC differentiation is disrupted; olfactory axons accumulate in the ventromedial olfactory nerve layer and fewer olfactory receptor neurons express the maturation marker OMP (most likely owing to the failure of axonal targeting). Furthermore, GnRH neurons clump together in the periphery and a smaller proportion enters the forebrain. Our data suggest that human Sox10 mutations cause Kallmann's syndrome by disrupting the differentiation of OECs, which promote embryonic olfactory axon targeting and hence olfactory receptor neuron maturation, and GnRH neuron migration to the forebrain.