bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract IA21: Immune mobilizing TCR therapies against cancer (ImmTAC): A novel class of antigen-specific tumor immunotherapy
Authors: Coughlin Christina M.
Published: November 2016

Cancer immunosuppression prevents the effective activation of antigen-specific cytotoxic T cell responses against tumor cells. The activation of tumor-specific responses has the potential to halt the progression of cancer and, in some circumstances, eradicate it. Designing the therapeutic interventions that can achieve this intended mechanism of action (T cell eradication of tumors) aims to harness the known specificity of the T cell: target cell interaction to simultaneously a) lead to death of tumor target cells expressing the antigen and b) to limit surrounding tissue damage and thus manage potential toxicity. Previous design approaches of bispecific therapeutic molecules to redirect T cell responses against cancer cells have utilized antibody binding domains to recognize tumor cell-surface proteins. These first generation bi-specifics have proven efficacy in hematologic malignancies, and novel approaches such as TCR targeting have the goal of enhancing activity in solid tumor settings. The ImmTACs (immune-mobilizing monoclonal TCRs against cancer) are a new class of bispecific therapeutic molecule, utilizing the physiologic antigen recognition system of the T cell, the monoclonal T cell receptor (TCR), as the targeting effector fused to an anti-CD3 domain. The soluble TCRs have been engineered to possess extremely high affinity for their tumor antigen peptide-HLA complex. ImmTACs thus overcome the problem of low affinity tumor-specific T cells imposed by thymic selection, and provide a means to target intracellular tumor antigens not accessible to antibody binding domains. The ImmTACs drive recruitment of polyclonal T cells to the tumor, resulting in potent redirected T cell response and tumor cell destruction in an antigen-specific manner. The first ImmTAC tested in the clinic is IMCgp100, an engineered TCR recognizing the gp100 melanoma antigen in the context of HLA-A2 with promising, preliminary single agent activity in both cutaneous and uveal melanoma.

Citation Format: Christina M. Coughlin. Immune mobilizing TCR therapies against cancer (ImmTAC): A novel class of antigen-specific tumor immunotherapy [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr IA21.
Bradykinin Contributes to Sympathetic and Pressor Responses Evoked by Activation of Skeletal Muscle Afferents P2X in Heart Failure
Authors: Xing Jihong , Li Jianhua
Published: November 2016

Background/Aims: Published data suggest that purinergic P2X receptors of muscle afferent nerves contribute to the enhanced sympathetic nervous activity (SNA) and blood pressure (BP) responses during static exercise in heart failure (HF). In this study, we examined engagement of bradykinin (BK) in regulating responses of SNA and BP evoked by P2X stimulation in rats with HF. We further examined cellular mechanisms responsible for BK. We hypothesized that BK potentiates P2X currents of muscle dorsal root ganglion (DRG) neurons, and this effect is greater in HF due to upregulation of BK kinin B2 and P2X3 receptor. As a result, BK amplifies muscle afferents P2X-mediated SNA and BP responses. Methods: Renal SNA and BP responses were recorded in control rats and rats with HF. Western Blot analysis and patch-clamp methods were employed to examine the receptor expression and function of DRG neurons involved in the effects of BK. Results: BK injected into the arterial blood supply of the hindlimb muscles heightened the reflex SNA and BP responses induced by P2X activation with α,β-methylene ATP to a greater degree in HF rats. In addition, HF upregulated the protein expression of kinin B2 and P2X3 in DRG and the prior application of BK increased the magnitude of α,β-methylene ATP-induced currents in muscle DRG neurons from HF rats. Conclusion: BK plays a facilitating role in modulating muscle afferent P2X-engaged reflex sympathetic and pressor responses. In HF, P2X responsivness is augmented due to increases in expression of kinin B2 and P2X3 receptors and P2X current activity.
Targeting Dynamin 2 as a Novel Pathway to Inhibit Cardiomyocyte Apoptosis Following Oxidative Stress
Authors: Gao Danchen , Yang Jian , Wu Yutao , Wang Qiwen , Wang Qiaoling , Lai En Yin , Zhu Jianhua
Published: November 2016

Background/Aims: Inhibition of Drp-1-mediated mitochondrial fission limits reactive oxygen species (ROS) production and apoptosis in cardiomyocytes subjected to ischemia/reperfusion injury. It remains unknown if Dynamin 2 inhibition results in similar protective effects. Here we studied the role of Dynamin 2 in cardiomyocyte oxidative stress-induced apoptosis and ROS production. Methods: The effect of lentiviral shRNA (lv5-shRNA) mediated Dynamin 2 knockdown on apopotosis, mitochondria, and ROS production were studied in neonatal mouse cardiomycytes, which were further treated with either selective Drp1 inhibitor mdivi-1 or the Dynamin 2/Drp1 inhibitor Dynasore. Apoptosis was evaluated by flow cytometry. Mitochondrial morphology and transmembrane potential (ΔΨm) were studied by confocal microscopy, and ROS production was detected by dichlorofluorescein diacetate. Results: Inhibition of Drp1 and Dynamin 2 protected against mitochondrial fragmentation, maintained ΔΨm, attenuated cellular ROS production and limited apoptosis. Moreover, Lv5-shRNA mediated knockdown of Dynamin 2 alleviated mitochondrial fragmentation, and reduced both ROS production and oxidative stress-induced apoptosis. The protective effects of Dynamin 2 knockdown were enhanced by Dynasore, indicating an added benefit. Conclusions: Oxidative stress-induced apoptosis and ROS production are attenuated by not only Drp1 inhibition but also Dynamin 2 inhibition, implicating Dynamin 2 as a mediator of oxidative stress in cardiomyocytes.
Prognostic Value of Red Blood Cell Distribution Width on Bleeding Events in Nonvalvular Atrial Fibrillation Patients Taking Dabigatran (110 mg b.i.d.) after Catheter Ablation
Authors: Zhang Qing , Qin Yao , Zhao Dong-sheng , Zhao Hai-ping , Zhou Lei
Published: November 2016

Objectives: Recent research has indicated that red blood cell distribution width (RDW) is associated with the prognosis of cardiovascular diseases such as chronic heart failure and coronary heart disease. We aimed to study the predictive value of RDW for bleeding events in patients with nonvalvular atrial fibrillation (NVAF) during the administration of 110 mg of dabigatran twice a day after catheter ablation. Methods: One hundred and seventy-two NVAF patients who were hospitalized and received catheter ablation in Jiangsu Provincial People's Hospital from January 2014 to January 2015 were enrolled (110 mg of dabigatran was administered orally to outpatients preoperatively twice a day for 3 weeks). The enrolled patients were divided into the high RDW (>12.8%) group (n = 85) and the low RDW (≤12.8%) group (n = 87) according to the median RDW. The activated partial thromboplastin time (APTT) at dabigatran trough concentration was also detected. Patients were followed up for 3 months to observe the occurrence of bleeding events, and the predictive value of RDW as well as APTT for bleeding events was assessed from receiver-operating characteristic (ROC) analyses. Results: In all patients, preoperatively, no bleeding events were observed and the APTT did not exceed twice the normal upper limit. Thirteen cases of bleeding events, all minor bleeding, occurred after a 3-month follow-up: 3 of gingival bleeding, 3 of urinary tract bleeding, 3 conjunctival hemorrhages and 4 subcutaneous hemorrhages. The incidence of bleeding events in the low RDW group was lower than in the high RDW group (3.4 vs. 11.8%, p = 0.039). The areas under the ROC curve for RDW and APTT to predict the occurrence of bleeding events were 0.737 (cutoff point 13.25%; p < 0.05) and 0.558 (p > 0.05), respectively. Conclusion: RDW was associated with the occurrence of bleeding events in NVAF patients on dabigatran (110 mg twice a day) after ablation, while also being an independent predictor of bleeding events. RDW had superior predictive value for bleeding events over APTT when APTT did not exceed twice the normal upper limit.
Effect of Melatonin on Telocytes in the Seminal Vesicle of the Soay Ram: An Immunohistochemical, Ultrastructural and Morphometrical Study
Authors: Abd-Elhafeez Hanan H. , Mokhtar Doaa M. , Hassan Ahmed H.S.
Published: November 2016

Telocytes (TCs) are a special type of interstitial cell with characteristic cellular processes that are described in many organs. The current study aimed to investigate TCs in seminal vesicles of the Soay ram responding to melatonin treatment during the nonbreeding season by conventional immunohistochemical stains, and to detect the ultrastructural and morphometrical changes of TCs. TCs in the control group showed a broad range of staining affinity and also reacted positively to CD117/c-kit, CD34, desmin, S-100 protein, and progesterone and estrogen receptors alpha, while after melatonin treatment a strong reaction against these 6 antibodies was recorded. Electron microscopically, TCs in the control group were characterized by a small cell body with distinct long cytoplasmic extensions called telopodes (Tps). Tps had alternation of the thin segment (podomers) and dilated segments (podoms), in which the latter accommodate mitochondria, rough endoplasmic reticulum and caveolae. TCs and their Tps were interconnected by homo- and heterocellular junctions and form a wide network to communicate between different cell types. Tps showed close contact with immune cells, progenitor stem cells, smooth muscle cells and other interstitial cells. Melatonin caused a significant increase in the number of TCs, length of Tps, and number and diameter of secretory vesicles. Also, the melatonin-treated group showed exaggerated secretory activity in the form of a massive release of secretory vesicles from Tps. Moreover, Tps showed an increase in their contact with blood and lymphatic capillaries, nerve endings and Schwann cells. In addition, the shedding of secretory structures (exosomes, ectosomes, and multivesicular bodies) was greater from Tps, which were involved in paracrine signaling in the melatonin-treated group. The length and ramifications of Tps together with the intercellular junctions and the releasing of shed vesicles or exosomes assumed an essential role of TCs in intercellular signaling and coordination. On the basis of their distribution and morphology, we investigated whether the different locations of TCs could be associated with different roles.
Post-Discharge Survival Outcomes of Patients with Advanced Cancer from the University of Texas MD Anderson Cancer Center Investigational Cancer Therapeutics (Phase I Trials) Inpatient Unit
Authors: Kinahan Holly , Maiti Abhishek , Hess Kenneth , Dempsey Jennifer , Beatty Laura , Baldwin Sarah , Hong David S. , Naing Aung , Fu Siqing , Tsimberidou Apostolia M. , Piha-Paul Sarina , Janku Filip , Karp Daniel , Reddy Suresh , Yennu Sriram , Epner Daniel , Bruera Eduardo , Meric-Bernstam Funda , Falchook Gerald , Subbiah Vivek
Published: November 2016

Background: Patients with advanced cancer who progress on standard therapy are potential candidates for phase I clinical trials. Due to their aggressive disease and complex comorbid conditions, these patients often need inpatient admission. This study assessed the outcomes of such patients after they were discharged to hospice care. Patients and Methods: We performed a retrospective analysis of patients with solid tumor malignancies who were discharged to hospice care from the inpatient service. Results: One hundred thirty-three patients were included in the study cohort. All patients had metastatic disease and an Eastern Cooperative Oncology Group performance status ≥3. The median survival after discharge to hospice from an inpatient setting was 16 days, with a survival rate of 5% at 3 months after discharge. The median survival after the last cancer treatment was 46 days, with survival of 17% at 3 months, and 5% at 6 months. Patients with lactate dehydrogenase (LDH) >618 IU/L had a median post-discharge survival of 11 days versus 20 days for patients with LDH ≤618 IU/L. Conclusions: Patients with metastatic cancer participating in phase I trials who have poor performance status and require inpatient admission have a very short survival after discharge to hospice. A high LDH level predicts an even shorter survival.
Tissue-Derived Signals for Mesenchymal Stem Cell Stimulation: Role of Cardiac and Umbilical Cord Microenvironments
Authors: Robert Anny Waloski , Schittini Andressa Vaz , Marchini Fabricio Klerynton , Batista Michel , Affonso Da Costa Marise Brenner , Senegaglia Alexandra Cristina , Brofman Paulo Roberto Slud , Abud Ana Paula Ressetti , Stimamiglio Marco Augusto
Published: November 2016

The tissue microenvironment regulates such stem cell behaviors as self-renewal and differentiation. Attempts to mimic components of these microenvironments could provide new strategies for culturing and directing the behavior of stem cells. The aim of the present study was to mimic cardiac and umbilical cord tissue microenvironments in vitro and compare the resulting bone marrow-derived mesenchymal stem cell (BM-MSC) behaviors. We generated tissue microenvironments using conditioned medium (CM) and extracellular matrix (ECM) samples obtained from human heart and umbilical cord tissue explant cultures and by tissue decellularization. Mass spectrometry and immunostaining were used to characterize and determine the specific protein profiles of the ECMs and CMs. We demonstrated that the ECMs and CMs were not cytotoxic to BM-MSCs and could thus be tested via cell culture. The BM-MSCs showed a higher proliferation rate when cultured with umbilical cord-derived CM compared with the other analyzed conditions. Furthermore, the ECMs increased cell adhesion and migration. However, although the conditions tested in this work were able to maintain the viability and affect the proliferation, adhesion and migration of BM-MSCs in vitro, mimicking tissue microenvironments using ECM and CM was not sufficient to induce the cardiomyogenic differentiation of BM-MSCs. The present study provides a thorough characterization of the biological activity of these ECMs and CMs in human BM-MSC cultures.
Discurso soberano performativo-metateatral no Anfritrião de Plauto: sobre homens e deuses
Authors: Gonçalves Rodrigo Tadeu
Published: November 2016

Este artigo analisa a peça Anfitrião de Plauto a partir da proposição de uma discursividade de viés sofístico-demiúrgico a partir da presença de personagens divinos (Mercúrio e Júpiter) e dos efeitos teatrais e metateatrais de suas intervenções autoconscientes no desenrolar do enredo, desde o longo prólogo de Mercúrio até os semi-prólogos dos dois deuses a cada reinício de unidades estruturais (identificadas como arcos por C. W. Marshall). Procuro avaliar de que maneira Plauto maneja a discursividade do poder divino a fim de mascarar o jogo teatral dentro da peça, com ênfase na autoconsciência performativa do discurso de Mercúrio e de Júpiter.
O poder do rei na tragédia de Eurípides
Authors: Ribeiro Junior Wilson Alves
Published: November 2016

Do ponto de vista histórico, a instituição dos reis gregos é insuficientemente documentada e sua exata natureza está ainda por se revelar. A julgar pela obra dos poetas arcaicos e clássicos, no entanto, as características da realeza ficaram bem gravadas na memória dos gregos do Período Clássico. Nesta oportunidade, foram selecionadas e estudadas algumas passagens da tragédia de Eurípides nas quais a participação do rei pode detalhar ou esclarecer alguns aspectos do poder monárquico nas antigas comunidades gregas e seu reflexo no imaginário dos gregos do século V a.C.
Low Body Mass Index, Serum Creatinine, and Cause of Death in Patients Undergoing Percutaneous Coronary Intervention
Authors: Goel Kashish , Gulati Rajiv , Reeder Guy S. , Lennon Ryan J. , Lewis Bradley R. , Behfar Atta , Sandhu Gurpreet S. , Rihal Charanjit S. , Singh Mandeep
Published: November 2016

Background

Low body mass index (
BMI
) and serum creatinine are surrogate markers of frailty and sarcopenia. Their relationship with cause‐specific mortality in elderly patients undergoing percutaneous coronary intervention is not well studied.

Methods and Results

We determined long‐term cardiovascular and noncardiovascular mortality in 9394 consecutive patients aged ≥65 years who underwent percutaneous coronary intervention from 2000 to 2011.
BMI
and serum creatinine were divided into 4 categories. During a median follow‐up of 4.2 years (interquartile range 1.8–7.3 years), 3243 patients (33.4%) died. In the multivariable model, compared with patients with normal
BMI
, patients with low
BMI
had significantly increased all‐cause mortality (hazard ratio [
HR
] 1.4, 95%
CI
1.1–1.7), which was related to both cardiovascular causes (HR 1.4, 95% CI 1.0–1.8) and noncardiovascular causes (HR 1.4, 95% CI 1.06–1.9). Compared with normal
BMI
, significant reduction was noted in patients who were overweight and obese in terms of cardiovascular mortality (overweight: HR 0.77, 95% CI 0.67–0.88; obese: HR 0.80, 95% CI 0.70–0.93) and noncardiovascular mortality (overweight: HR 0.85, 95% CI 0.74–0.97; obese: HR 0.82, 95% CI 0.72–0.95). In a multivariable model, in patients with normal
BMI
, low creatinine (≤0.70 mg/dL) was significantly associated with increased all‐cause mortality (HR 1.8, 95% CI 1.3–2.5) and cardiovascular mortality (HR 2.3, 95% CI 1.4–3.8) compared with patients with normal creatinine (0.71–1.0 mg/dL); however, this was not observed in other
BMI
categories.

Conclusions

We identified a new subgroup of patients with low serum creatinine and normal
BMI
that was associated with increased all‐cause mortality and cardiovascular mortality in elderly patients undergoing percutaneous coronary intervention. Low
BMI
was associated with increased cardiovascular and noncardiovascular mortality. Nutritional support, resistance training, and weight‐gain strategies may have potential roles for these patients undergoing percutaneous coronary intervention.
Short‐Term Risk of Bleeding During Heparin Bridging at Initiation of Vitamin K Antagonist Therapy in More Than 90 000 Patients With Nonvalvular Atrial Fibrillation Managed in Outpatient Care
Authors: Bouillon Kim , Bertrand Marion , Boudali Lotfi , Ducimetière Pierre , Dray‐Spira Rosemary , Zureik Mahmoud
Published: November 2016

Background

Several studies have recently examined the risks of bleeding and of ischemic stroke and systemic embolism associated with perioperative heparin bridging anticoagulation in patients with nonvalvular atrial fibrillation. However, few studies have investigated bridging risks during vitamin K antagonist initiation in outpatient settings.

Methods and Results

A retrospective cohort study was conducted on individuals starting oral anticoagulation between January 2010 and November 2014 for nonvalvular atrial fibrillation managed in outpatient care and identified from French healthcare insurance. Bleeding and ischemic stroke and systemic embolism events were identified from the hospitalization database. Adjusted hazard ratios with 95%
CI
were estimated using Cox models during the first and 2 following months of anticoagulation. Of 90 826 individuals, 30% had bridging therapy. A total of 318 (0.35%) cases of bleeding and 151 (0.17%) ischemic stroke and systemic embolism cases were identified during the first month of follow‐up and 231 (0.31%) and 122 (0.16%) during the 2 following months, respectively. At 1 month of follow‐up, the incidence of bleeding was higher in the bridged group compared with the nonbridged group (0.47% versus 0.30%;
P
<0.001), and this increased risk persisted after adjustment for covariates (hazard ratio=1.60; 95%
CI
, 1.28–2.01). This difference disappeared after the first month of treatment (0.93; 0.70–1.23). No significant difference in the occurrence of ischemic stroke and systemic embolism was observed either at 1 month of follow‐up or later.

Conclusions

At vitamin K antagonist initiation for nonvalvular atrial fibrillation managed in ambulatory settings, bridging therapy is associated with a higher risk of bleeding and a similar risk of arterial thromboembolism compared with no bridging therapy.
Support for the underrepresented sex: new descriptions of scutacarid males (Acari, Heterostigmatina)
Authors: JAGERSBACHER-BAUMANN JULIA , EBERMANN ERNST
Published: November 2016

Based on males gained from laboratory cultures, nine new descriptions and one redescription of scutacarid males are given: the respective species are Heterodispus foveatus Jagersbacher-Baumann and Ebermann 2012, Imparipes dispar Rack, 1964, Lamnacarus ornatus Balogh and Mahunka, 1963, Scutacarus acarorum (Goeze, 1780), S. deserticolus Mahunka, 1969, S. ellipticus Karafiat, 1959, S. longipes Rack, 1975, S. longitarsus (Berlese, 1905), S. tackei Willmann, 1942 and S. tyrrhenicus Ebermann, 1986. The taxonomic relevance of male morphology is evaluated. It reveals a strong potential for differentiating between species, and possible characters diagnostic for scutacarid genera are discussed. Within Heterostigmatina, males of Scutacaridae show the most derived characters.
Predictability and Dynamics of Warm-Core Mesoscale Vortex Formation with the 8 May 2009 “Super Derecho” Event
Authors: Grunzke Caleb T. , Evans Clark
Published: November 2016

The predictability and dynamics of the warm-core mesovortex associated with the northern flank of the 8 May 2009 “super derecho” event are examined by coupling the Advanced Research Weather Research and Forecasting Model with the ensemble adjustment Kalman filter implementation within the Data Assimilation Research Testbed facility. Cycled analysis started at 1200 UTC 2 May 2009, with observations assimilated every 6 h until 1200 UTC 7 May 2009, at which time a 50-member ensemble of 36-h convection-allowing ensemble forecasts were launched. The ensemble forecasts all simulated a mesoscale convective system, but only 7 out of 50 members produced a warm-core mesovortex-like feature similar in intensity to the observed mesovortex.

Ensemble sensitivity and composite analyses were conducted to analyze the environmental differences between ensemble members. A more amplified upstream upper-level trough near the time of observed convection initiation is associated with a stronger simulated mesovortex. The amplification of the trough results in increases in the magnitudes of the low-level jet and thermal gradient. Consequently, more moisture is transported poleward into western Kansas, leading to earlier convection initiation in ensemble members with the strongest mesovortices. A circulation budget is performed on the ensemble members with the strongest (member 10) and weakest (member 5) time-averaged circulations. The ascending front-to-rear flow, descending rear-to-front flow, and divergent low-level flow of an MCS are more prominent in member 10, which is hypothesized to allow for the convergence of more background cyclonic absolute vorticity and, thus, facilitating the development of a stronger mesovortex.
Observed and Projected Changes in United States Tornado Exposure
Authors: Strader Stephen M. , Ashley Walker S. , Pingel Thomas J. , Krmenec Andrew J.
Published: November 2016

This study examines how tornado risk and societal exposure interact to create tornado disaster potential in the United States. Finescale historical and projected demographic data are used in a set of region-specific Monte Carlo tornado simulations to reveal how societal development has shaped, and will continue to shape, tornado disaster frequency and consequences. Results illustrate that although the U.S. Midwest contains the greatest built-environment exposure and the central plains experience the most significant tornadoes, the midsouth contains the greatest tornado disaster potential. This finding is attributed to the relatively elevated tornado risk and accelerated growth in developed land area that characterizes the midsouth region. Disaster potential is projected to amplify in the United States due to increasing built-environment development and its spatial footprint in at-risk regions. In the four regions examined, both average annual tornado impacts and associated impact variability are projected to be as much as 6 to 36 times greater in 2100 than 1940. Extreme annual tornado impacts for all at-risk regions are also projected to nearly double during the twenty-first century, signifying the potential for greater tornado disaster potential in the future. The key lesson is that it is the juxtaposition of both risk and societal exposure that drive disaster potential. Mitigation efforts should evaluate changes in tornado hazard risk and societal exposure in light of land-use planning, building codes, and warning dissemination strategies in order to reduce the effects of tornadoes and other environmental hazards.
Do cash transfers help the poor during trade liberalization? Evidence from Laos
Authors: Kyophilavong Phouphet , Lassachack Xaignasack , Volavong Thanouxay
Published: November 2016

Our objective is to assess the impact of trade liberalization and cash transfer programs on poverty and income distribution in Laos.We use the computable general equilibrium model and micro-simulation to assess the impact of transfer programs during trade liberalization.The results of this study indicate that cash transfers reduce poverty and narrow income inequality during trade liberalization. Policy-makers should promote development and implementation of cash transfer in Laos in order to protect poor people from the external shocks such the impact of trade liberalization. This finding might have significant impact on promotion of cash transfer programs in order to reduce poverty and income inequality.This is the first paper to investingate the impact of a cash transfer program on poverty in Laos during trade liberalization.
Interventions for female drug-using offenders
Authors: Perry Amanda E. , Neilson Matthew , James Marissa Martyn-St , Glanville Julie M. , Woodhouse Rebecca , Hewitt Catherine
Published: November 2016

This is an updated version of a Cochrane review first published in Issue 3, 2006 (Perry 2006). The review represents one in a family of four reviews focusing on the effectiveness of interventions in reducing drug use and criminal activity for offenders. This specific review considers interventions for female drug-using offenders.
Cervantes and Don Quixote de la Mancha
Authors: Oyebode Femi
Published: November 2016

Miguel de Cervantes, the most influential writer in Spanish literature, created two of the most recognisable fictional characters, Don Quixote de la Mancha and Sancho Panza, in 1605. His novel The Ingenious Hidalgo Don Quixote de la Mancha is regarded as the first modern novel and first international best seller. This article, in the 400th anniversary year of Cervantes' death, introduces Cervantes' biography, discusses the enduring features of his classic novel and explores the value and importance of the novel for psychiatry.
Transcranial magnetic stimulation in clinical practice
Authors: Hardy Sheila , Bastick Lorraine , O'Neill-Kerr Alex , Sabesan Priyadharshini , Lankappa Sudheer , Palaniyappan Lena
Published: November 2016

Up to 40% of people with depression do not recover following standard treatments such as medication and psychotherapy. Transcranial magnetic stimulation (TMS) is a treatment used worldwide for adult patients with severe clinical depression when antidepressants have repeatedly failed to control their symptoms. This article explains the use of TMS in clinical practice.
Auditory hallucinations in schizophrenia: helping patients to develop effective coping strategies
Authors: Turkington Douglas , Lebert Latoyah , Spencer Helen
Published: November 2016

Auditory hallucinations (voices) are the most common symptom in schizophrenia, occurring in 70% of those with the diagnosis. A proportion respond to antipsychotic medication, but despite adequate concordance with prescribed medication, voices may still remain. Voice hearers often inadvertently activate coping strategies that maintain the symptoms and linked distress. Assessment can identify ineffective strategies. Effective strategies can then be initiated, starting with distraction to reduce distress in the short term and leading to focusing approaches that give an improved understanding of voice maintenance. This article describes how to recognise voice hearers' ineffective coping strategies and how to teach effective approaches that are a crucial catalyst in the recovery process.
What to do with female drug-using offenders?
Authors: Rix Keith J. B.
Published: November 2016

Female drug-using offenders are a large but under-researched and vulnerable population with specific needs. Only a handful of randomised controlled trials of interventions for this population are of sufficient quality to shed light on what might work to reduce their criminal activity and drug use, and interpretation of the results of most of these trials is limited by an ‘unclear’ risk of bias due to a lack of descriptive information. Better-quality research is needed to inform practitioners and policy makers. In the meantime, this month's Cochrane Corner review provides cautious support for the use of some psychosocial treatments, particularly if delivered in a gender-responsive way addressing issues of abuse and victimisation, in the expectation that re-imprisonment can be prevented, even if there is no proven effect on re-arrest rates and only uncertain effects on substance use.
Ten books
Authors: Moncrieff Joanna
Published: November 2016

Writing this essay on ten books has been incredibly enjoyable and surprisingly helpful in clarifying my ideas. Before I wrote it I had no idea my tastes were so consistent – some might say predictable! The following list includes classic texts that have had a fundamental influence on my thinking, and books that highlight important issues in an original way.
Sexual violence and abuse and the care programme approach
Authors: Brooker Charles G. D. , Tocque Karen , Brown Martin , Kennedy Angela
Published: November 2016

In 2008 it became policy that all those on the care programme approach were assessed for sexual violence/abuse. The implementation of this policy was assessed 8 years on. The findings of a survey and data request to Health and Social Care Information Centre are disappointing. We argue that this important initiative needs to be reinvigorated.
Gestational Chronodisruption Impairs Circadian Physiology in Rat Male Offspring, Increasing the Risk of Chronic Disease
Authors: Mendez Natalia , Halabi Diego , Spichiger Carlos , Salazar Esteban R. , Vergara Karina , Alonso-Vasquez Pamela , Carmona Pamela , Sarmiento Jose M. , Richter Hans G. , Seron-Ferre Maria , Torres-Farfan Claudia
Published: November 2016

Chronic exposure to light at night, as in shift work, alters biological clocks (chronodisruption), negatively impacting pregnancy outcome in humans. Actually the interaction of maternal and fetal circadian systems could be a key factor determining a fitting health in adults. We propose that chronic photoperiod shift (CPS) during pregnancy alter maternal circadian rhythms and impair circadian physiology in the adult offspring, increasing health risks. Pregnant rats were exposed to normal photoperiod (12 h light, 12 h dark) or to CPS until 85% of gestation. The effects of gestational CPS were evaluated on the mother and adult offspring. In the mother we measured rhythms of heart rate, body temperature, and activity through gestation and daily rhythms of plasma variables (melatonin, corticosterone, aldosterone, and markers of renal function) at 18 days of gestation. In adult offspring, we measured rhythms of the clock gene expression in the suprachiasmatic nucleus (SCN), locomotor activity, body temperature, heart rate, blood pressure, plasma variables, glucose tolerance, and corticosterone response to ACTH. CPS altered all maternal circadian rhythms, lengthened gestation, and increased newborn weight. The adult CPS offspring presented normal rhythms of clock gene expression in the SCN, locomotor activity, and body temperature. However, the daily rhythm of plasma melatonin was absent, and corticosterone, aldosterone, renal markers, blood pressure, and heart rate rhythms were altered. Moreover, CPS offspring presented decreased glucose tolerance and an abnormal corticosterone response to ACTH. Altogether these data show that gestational CPS induced long-term effects on the offspring circadian system, wherein a normal SCN coexists with altered endocrine, cardiovascular, and metabolic function.
Why Does Canadian English Use try to but British English Use try And? Let's Try and/to Figure It Out
Authors: Brook Marisa , Tagliamonte Sali A.
Published: November 2016

This article examines the variation between try to and try and in two major varieties of English, Canadian and British. Embedding our research in earlier studies of corpora, we extend our knowledge of this phenomenon to vernacular community-based dialect data. Comparative sociolinguistic analysis and statistical methods establish the significant mechanisms underlying the alternation. Unexpected social patterns in the United Kingdom point to a change in the social evaluation of try and. Also, despite divergent external influences, there are similar internal constraints of tense and lexical verb. The authors propose that these constraints are a holdover from reanalysis in the seventeenth-century and the semantic fossilization of try and before certain verbs. They conclude that social factors may divide the major varieties of English, but longitudinal linguistic patterns endure.
The functions of long noncoding RNAs in development and stem cells
Authors: Perry Rotem Ben-Tov , Ulitsky Igor
Published: November 2016

Eukaryotic genomes are pervasively transcribed, with tens of thousands of RNAs emanating from uni- and bi-directional promoters and from active enhancers. In vertebrates, thousands of loci in each species produce a class of transcripts called long noncoding RNAs (lncRNAs) that are typically expressed at low levels and do not appear to give rise to functional proteins. Substantial numbers of lncRNAs are expressed at specific stages of embryonic development, in many cases from regions flanking key developmental regulators. Here, we review the known biological functions of such lncRNAs and the emerging paradigms of their modes of action. We also provide an overview of the growing arsenal of methods for lncRNA identification, perturbation and functional characterization.
Structure of a Gold(III) Hydroxide and Determination of Its Solubility
Authors: Kawamoto Daisuke , Ando Hiroaki , Ohashi Hironori , Kobayashi Yasuhiro , Honma Tetsuo , Ishida Tamao , Tokunaga Makoto , Okaue Yoshihiro , Utsunomiya Satoshi , Yokoyama Takushi
Published: November 2016

A representative gold(III) complex ion ([AuCl4]−), successively hydrolyzes to form [AuCl4−n(OH)n]− (n = 0–4) in aqueous solution as the pH increases and, finally, precipitates. It has been referred to as “gold(III) hydroxide” for the past fifty years. However, whether the precipitate is gold(III) hydroxide (Au(OH)3) or hydrous gold(III) oxide (Au2O3·nH2O) has remained uncertain. Few studies have been conducted to determine its chemical and physical properties. The aim of this investigation is to identify the precipitate and to determine its solubility. The precipitate was X-ray amorphous. Based on the transmission electron microscopy (TEM) observation, the shape was spherical and the particle diameter was approximately 9 nm. From the results of 197Au Mössbauer spectroscopy, Au L3-edge X-ray absorption (XA) spectroscopy and thermogravimetry/differential thermal analysis (TG/DTA) measurements, the precipitate composition was estimated to be Au(OH)3. Based on the composition, its structure was proposed to be a linear polymer. Moreover, its solubility at 298 K was determined to be 0.00120 g/100 g of H2O. This chemical and physical properties information of Au(OH)3 is essential for gold chemistry, for example, for preparing supported gold catalyst.
Political Economy of Redistribution in the United States in the Aftermath of World War II—Evidence and Theory
Authors: Beetsma Roel , Cukierman Alex , Giuliodori Massimo
Published: November 2016

We present legislative, historical and statistical evidence of a substantial upward ratchet in transfers and taxes in the US due to World War II. This finding is explained within a political-economy framework with defense spending responding to a war threat and a median voter in the population who interacts with a (richer) agenda setter in Congress in setting redistribution. While the setter managed to cap redistribution before the War, the War itself raised the status quo tax burden and improved tax collection technology, strengthening the bargaining power of the median voter as defense spending receded. This permanently raised the level of redistribution. (JEL D72, H11, H23, H56, N32, N42)
Nonparametric Evidence on the Effects of Financial Incentives on Retirement Decisions
Authors: Manoli Day , Weber Andrea
Published: November 2016

This paper presents new evidence on the effects of retirement benefits on labor force participation decisions. The analysis is based on a mandated rule for employer-provided retirement benefits in Austria that creates discontinuities in the incentives for workers to delay retirement. The paper presents graphical evidence on labor supply responses and develops a conceptual framework that accounts for the dynamic incentive structure and for adjustment frictions. Using bunching methods, a semi-elasticity of participation is estimated, which ranges from 0.1 to 0.3 and is highest for incentives targeted at a delay in retirement by 6 to 9 months. (JEL D14, D91, H55, J22, J26, J65)
An Empirical Analysis of Self-Enforcement Mechanisms: Evidence from Hotel Franchising
Authors: Kosová Renáta , Sertsios Giorgo
Published: November 2016

The relational contracts literature suggests that a principal can improve contract self-enforceability by specifying initial requirements that increase the agent’s ex post rents. Initial requirements specified in hotel franchise agreements—size and quality tier of the hotel—offer a unique empirical setting to test this. Using proprietary data on 5,547 new franchised hotels and their revenues, we find that hotels far away from their franchisor’s headquarters are larger, more likely to belong to a high quality tier, and generate higher revenues ex post. This supports the idea that the agent’s ex post rents can serve as a substitute to the principal’s monitoring intensity in the mitigation of agency problems. Our findings shed light on how formal contract terms can influence informal (relational) contracts between business partners.

This paper was accepted by Bruno Cassiman, business strategy.
An outstanding inspection should be just the start
Authors: Tanuku Purnima
Published: November 2016

What do you worry about most? Chances are that an Ofsted visit is high on the list, but while the outcome is important, it is vital that, even if you are outstanding, it is used as a tool for improvement.
With added possibilities
Authors: Chapman Ailsa
Published: November 2016

Whatever activity you might have planned, you can guarantee that children will take it in different and novel directions, making learning more powerful, which is what happened when I introduced water beads.
Skipping with ropes to the beats of a hopping tune
Authors: Harries Judith
Published: November 2016

The sixth article in a series that will explore traditional games takes a look at an activity that has its origins in the mist of time, but was certainly popular by the time of the ancient Greeks – skipping.
Reliability of the Danish Abbey Pain Scale in severely demented and non-communicative older patients
Authors: Gregersen Merete , Melin Anne Sophie , Nygaard Ida Sofie , Nielsen Christina H , Beedholm-Ebsen Mathilde
Published: November 2016

Aim:

To validate a Danish version of the observational Abbey Pain Scale (APS) in a geriatric ward.

Material and methods:

The study population consisted of 50 old patients (70+ years), consecutively admitted to the geriatric wards of Aarhus University Hospital, Denmark, and fulfilling one of the following inclusion criteria: Mini Mental State Examination (MMSE) < 5, delirium, non-communicative aphasia, or unconsciousness. APS has six subscales and ranges from 0 (no pain) to 18 (worst pain). Criterion validity was assessed by using Verbal Rating Scale (VRS) as the gold standard. Cohen's kappa (k) was the measure of agreement. Inter-rater reliability was measured by two independent ratings of the same patient at the same time and assessed by Intraclass Correlation Coefficient (ICC). Internal consistency between the subscales was analysed by Cronbach's Alpha. Responsiveness was tested if the first APS score was positive for pain. ‘Before’ and ‘after’ sum scores were compared by paired t-test.

Results:

We found poor agreement between APS and VRS (k=0.42). The inter-rater reliability was good (ICC=0.84). Cronbach's Alpha was 0.52 (fair agreement). In 66% of the patients, pain was observed and re-tested when an expected effect of analgesics had occurred. Of these, 88% reached a reduction on the APS sum-score (p<0.001).

Conclusion:

Our assessment of the Danish version of APS shows that this pain assessment scale should be considered as qualified and usable in severely demented and non-communicative older patients admitted to a geriatric ward.
Enhancing bereavement support skills using simulated neonatal resuscitation
Authors: Forster Elizabeth M , Donovan Helen
Published: November 2016

Neonatal death is one of the most challenging elements of nursing and midwifery practice and health professionals supporting parents following such a loss often develop their skills in bereavement care through experience and modelling from experienced peers. For student nurses and midwives who have limited exposure to neonatal death during their clinical experiences, developing the skills to support bereaved parents is a priority during their undergraduate education. Clinical simulations can aid student learning in this complex area of clinical practice and assist them to engage effectively in support for bereaved parents. This paper reports on a qualitative study where the use of neonatal resuscitation simulation is used to prepare a group of undergraduate (double degree) nurse midwives to support bereaved parents surrounding neonatal death. The findings indicate that this simulation can assist students to develop and reflect upon their bereavement support skills in the context of unexpected neonatal death. They also point to the need for equipping students with self care strategies to manage their personal responses to the highly emotive context of neonatal death and supporting the bereaved mother.
Lateral closing isosceles triangular osteotomy for the treatment of a post-traumatic cubitus varus deformity in children
Authors: Su Y. , Nan G.
Published: November 2016

Aims

Cubitus varus is the most common late complication of a supracondylar fracture of the humerus in children. Correction can be performed using one of a number of techniques of osteotomy but each has disadvantages. We describe a new technique for correcting post-traumatic cubitus varus using a lateral closing wedge isosceles triangular osteotomy.

Patients and Methods

A lateral closing wedge isosceles triangular osteotomy was performed in 25 patients (15 male and ten female with a mean age of 9.5 years (6 to 12)) between May 2010 and April 2013. All patients had cubitus varus secondary to malunion of a supracondylar fracture, with good function of the elbow and a full range of movement. The osteotomy lines were marked on the bone with an isosceles triangular template made before surgery, after which the osteotomy was performed leaving the medial cortex intact. Fixation was performed using two lateral 2 mm Kirschner (K)-wires and patients were immobilised in an above-elbow plaster. By six to eight weeks callus was present and the wires and cast were removed. Patients were reviewed at four and six weeks, three, six and 12 months and then every two years until skeletal maturity. Clinical and radiographic outcomes were categorised as excellent, good or poor.

Results

A total of 23 patients had an excellent and two had a good outcome at a mean final follow-up of 3.4 years (two to four). The mean post-operative carrying angle in the corrected elbow was 11.7° (7° to 18°). One patient fell, displacing the osteotomy, and needed revision of the fixation. No patient had a nerve injury.

Conclusion

A lateral isosceles triangular osteotomy and with K-wire fixation is a practical, effective, reliable, safe and simple method of correcting post-traumatic cubitus varus in children. It has inherent stability and excellent cosmesis without prominence of the lateral condyle. Cite this article: Bone Joint J 2016;98-B:1521–5.
The ‘three-legged stool’
Authors: Powell J. M. , Rai A. , Foy M. , Casey A. , Dabke H. , Gibson A. , Hutton M.
Published: November 2016

Many hospitals do not have a structured process of consent, the attainment of which can often be rather ‘last-minute’ and somewhat chaotic. This is a surprising state of affairs as spinal surgery is a high-risk surgical specialty with potential for expensive litigation claims. More recently, the Montgomery ruling by the United Kingdom Supreme Court has placed the subject of informed consent into the spotlight.

There is a paucity of practical guidance on how a consent process can be achieved in a busy clinical setting. The British Association of Spinal Surgeons (BASS) has convened a working party to address this need. To our knowledge this is the first example of a national professional body, representing a single surgical specialty, taking such a fundamental initiative.

In a hard-pressed clinical environment, the ability to achieve admission reliably on the day of surgery, in patients at ease with their situation and with little likelihood of late cancellation, will be of great benefit. It will reduce litigation and improve the patient experience.

Cite this article: Bone Joint J 2016;98-B:1427–30.
Periprosthetic fractures associated with total knee arthroplasty
Authors: Konan S. , Sandiford N. , Unno F. , Masri B. S. , Garbuz D. S. , Duncan C. P.
Published: November 2016

Fractures around total knee arthroplasties pose a significant surgical challenge. Most can be managed with osteosynthesis and salvage of the replacement. The techniques of fixation of these fractures and revision surgery have evolved and so has the assessment of outcome. This specialty update summarises the current evidence for the classification, methods of fixation, revision surgery and outcomes of the management of periprosthetic fractures associated with total knee arthroplasty.

Cite this article: Bone Joint J 2016;98-B:1489–96.