bluuebunny/crossref_metadata_2025 huggingface dataset:
A Preliminary Evaluation of the Ability of Keratotic Tissue to Act as a Prognostic Indicator of Hip Fracture Risk
Authors: Beattie J Renwick , Feskanich Diane , Caraher M Clare , Towler Mark R
Published: January 2018

Studies have shown that Raman spectroscopic analysis of fingernail clippings can help differentiate between post-menopausal women who have and who have not suffered a fracture. However, all studies to date have been retrospective in nature, comparing the proteins in nails sourced from women, post-fracture. The objective of this study was to investigate the potential of a prospective test for hip fracture based on spectroscopic analysis of nail tissue. Archived toenail samples from post-menopausal women aged 50 to 63 years in the Nurses’ Health Study were obtained and analysed by Raman spectroscopy. Nails were matched case-controls sourced from 161 women; 82 who underwent a hip fracture up to 20 years after nail collection and 81 age-matched controls. A number of clinical risk factors (CRFs) from the Fracture Risk Assessment (FRAX) tool had been assessed at toenail collection. Using 80% of the spectra, models were developed for increasing time periods between nail collection and fracture. Scores were calculated from these models for the other 20% of the sample and the ability of the score to predict hip fracture was tested in model with and without the CRFs by comparing the odds ratios (ORs) per 1 SD increase in standardised predictive values. The Raman score successfully distinguished between hip fracture cases and controls. With only the score as a predictor, a statistically significant OR of 2.2 (95% confidence interval [CI]: 1.5-3.1) was found for hip fracture for up to 20 years after collection. The OR increased to 3.8 (2.6-5.4) when the CRFs were added to the model. For fractures limited to 13 years after collection, the OR was 6.3 (3.0-13.1) for the score alone. The test based on Raman spectroscopy has potential for identifying individuals who may suffer hip fractures several years in advance. Higher powered studies are required to evaluate the predictive capability of this test.
Hospitalisation in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Nanayakkara Shane , Patel Hitesh C , Kaye David M
Published: January 2018

Heart failure is highly prevalent with more than 50% of cases being patients with a preserved ejection fraction (HFPEF), a figure that is projected to increase due to the changing risk factor landscape, in particular the ageing population. Overall mortality is similar to patients with heart failure with reduced ejection fraction (HFREF), as are the rates of hospitalisation. Patients with HFPEF have more comorbid conditions with fewer therapeutic options available. In this review, we explore the epidemiology of hospitalisation of HFPEF, the impact of current treatment modalities, and the potential of future therapies.
Consultancy in ‘failing schools’: Emerging issues
Authors: Dedering Kathrin
Published: January 2018

External consultancy in schools by those who do not belong to the teaching staff has always been an important factor in school development. Such consulting goes hand in hand with the idea that internal school development processes and their results can be influenced positively by external experts. This is even more so for failing schools – that is, those that are revealed to have serious quality deficiencies by the school inspection. (The term failing schools is used in this article as shorthand; the actual terminology, and the underlying thinking, varies between education systems.) This article considers how school development consultancy is exercised by external experts in schools that have been classified as failing. It draws on empirical findings in part from a research project with schools found to have serious deficiencies in the first round of school inspections in the German federal state of Lower Saxony. Our research reveals that the framework conditions under which the outcomes of the inspections are processed at failing schools (in particular, the follow-up inspection) influence the activities in the school in such a way that a specific type of consultancy and/or a specific procedure by the advisers becomes attractive for the schools. This sometimes works against a closer examination of contents, strategies and instruments in school development – although the consultancy contracts advise this. This article, therefore, deals with how external consultancy for school development would have to be designed conceptually in order to effectively support the development activities at failing schools.
Combined finite element and phase field method for simulation of austenite grain growth in the heat-affected zone of a martensitic steel weld
Authors: Shi L , Alexandratos SA , O’Dowd NP
Published: January 2018

Engineering components operating at high temperature often fail due to the initiation and growth of cracks in the heat-affected zone adjacent to a weld. Understanding the effects of microstructural evolution in the heat-affected zone is important in order to predict and control the final properties of welded joints. This study presents a combined finite element method and phase field method for simulation of austenite grain growth in the heat-affected zone of a tempered martensite (P91) steel weld. The finite element method is used to determine the thermal history of the heat-affected zone during gas tungsten arc welding of a P91 steel plate. Then, the calculated thermal history is included in a phase field model to simulate grain growth at various positions in the heat-affected zone. The predicted mean grain size and grain distribution match well with experimental data for simulated welds from the literature. The work lays the foundation for optimising the process parameters in welding of P91 and other ferritic/martensitic steels in order to control the final heat-affected zone microstructure.
On using robust Mahalanobis distance estimations for feature discrimination in a damage detection scenario
Authors: Yeager Mike , Gregory Bill , Key Chris , Todd Michael
Published: January 2018

In this study, a damage detection and localization scenario is presented for a composite laminate with a network of embedded fiber Bragg gratings. Strain time histories from a pseudorandom simulated operational loading are mined for multivariate damage-sensitive feature vectors that are then mapped to the Mahalanobis distance, a covariance-weighted distance metric for discrimination. The experimental setup, data acquisition, and feature extraction are discussed briefly, and special attention is given to the statistical model used for a binary hypothesis test for damage diagnosis. This article focuses on the performance of different estimations of the Mahalanobis distance metric using robust estimates for location and scatter, and these alternative formulations are compared to traditional, less robust estimation methods.
Environmental basis of primary biliary cholangitis
Authors: Tanaka Atsushi , Leung Patrick SC , Gershwin M Eric
Published: January 2018

Autoimmunity is a consequence of both genetic and environmental factors, occurring in genetically susceptible hosts with environmental triggers. While genome-wide association studies have revealed a number of susceptible genes contributing to etiology, the environmental triggers remain poorly understood. Primary biliary cholangitis, formally known as primary biliary cirrhosis, is considered a model autoimmune disease for which our group has extensively evaluated environmental factors involved in its etiology. Bacterial infection and xenobiotics have been proposed as candidate environmental factors that may explain tolerance breakdown and production of primary biliary cholangitis-specific antimitochondrial autoantibodies. Large-scale case-control studies have consistently detected an association of primary biliary cholangitis with urinary tract infections caused by Escherichia coli, as E. coli PDC-E2 is molecularly similar to human PDC-E2, the immunodominant target of AMAs. Another bacterium of interest is Novosphingobium aromaticivorans, a ubiquitous xenobiotic-metabolizing bacterium that produces lipoylated proteins, which are highly reactive with sera from primary biliary cholangitis patients. Regarding xenobiotics, case-control studies have suggested that frequent use of nail polish is associated with an increased susceptibility to primary biliary cholangitis. We found that 2-octynamide, the conjugate derived from 2-octynoic acid present in cosmetics, lipsticks, and some chewing gums, was unique in both its quantitative structure–activity relationship analysis and reactivity with primary biliary cholangitis sera. 2-nonyamide is another xenobiotic that also has the optimal chemical structure for xenobiotic modification of the PDC-E2 epitope, as demonstrated by the enhanced epitope recognition with AMA-positive PBC sera. Moreover, we found that C57BL/6 mice immunized with 2-octynoic acid-BSA possess many of the features characteristic to primary biliary cholangitis.

Impact statement

Autoimmunity is believed to develop in genetically susceptible hosts with triggers from the environment. Researchers have recently demonstrated that bacteria and xenobiotics commonly present in our environment are potential triggers of tolerance breakdown against autoantigens and autoimmunity, particularly in primary biliary cholangitis (PBC). The link between xenobiotics and PBC has been further confirmed with the establishment of PBC model mice by immunizing mice with xenobiotics.
FOXD3/FOXD4 is required for the development of hindgut in the rat model of anorectal malformation
Authors: Wang Luo-Jia , Wang Wei-Lin , Gao Hong , Bai Yu-Zuo , Zhang Shu-Cheng
Published: January 2018

Congenital anorectal malformation is the most common digestive tract malformation in newborns. It has been reported that FOXD3/FOXD4, a forkhead transcription factor, regulates the generation, migration, and differentiation of neural crest cells. However, whether FOXD3/FOXD4 takes part in anorectal malformation remains unclear. In the present study, we used ethylene thiourea to induce the animal models of anorectal malformation in rat embryos and to interrogate the role of FOXD3/FOXD4 in anorectal malformation pathogenesis. Hindgut samples of the animal models were collected at E15, E17, E19, and E21 days of age. The expression of FOXD3/FOXD4 was detected by immunohistochemistry, western blot, and quantitative real-time fluorescence PCR. By immunohistochemical staining, FOXD3/FOXD4 was observed in epithelial cells of the rectum and the anus both in normal and rat embryos with anorectal malformation. Expression level analysis by western blot indicated that FOXD3/FOXD4 expression increased in ethylene thiourea-induced anorectal malformation groups. mRNA expression as determined by quantitative real-time fluorescence PCR analysis was consistent with the western blot results. Tentative conclusions were drawn that FOXD3/FOXD4 is expressed in the hindgut in rat embryos and is upregulated in anorectal malformation. FOXD3/FOXD4 is required for the development of the hindgut, and its aberrant expression may be an important factor leading to the incidence of anorectal malformation.

Impact statement

Congenital anorectal malformation (ARM) is the most common digestive tract malformation in newborns. The pathophysiological ground remains unclear. In this study, we used animal models of ARM for the first time to interrogate the role of FOXD3/FOXD4 in ARM pathogenesis. The animal models of ARM were successfully induced by ethylene thiourea (ETU) in rat embryos providing a strong basis for pathogenesis study of this disease. Expression analysis of FOXD3/FOXD4 was carried out in these models, and the results shape a deeper understanding of FOXD3/FOXD4 being required for the normal development of the hindgut. The aberrant expression of FOXD3/FOXD4 may be an important factor leading to ARM incidence.
An efficient optimization algorithm for quadratic programming problem and its applications to mobile robot path planning
Authors: Cai Lei , Yang Juanjuan , Zhao Li , Wu Lan
Published: January 2018

The quadratic programming problem has broad applications in mobile robot path planning. This article presents an efficient optimization algorithm for globally solving the quadratic programming problem. By utilizing the convexity of univariate quadratic functions, we construct the linear relaxation programming problem of the quadratic programming problem, which can be embedded within a branch-and-bound structure without introducing new variables and constraints. In addition, a new pruning technique is inserted into the branch-and-bound framework for improving the speed of the algorithm. The global convergence of the proposed algorithm is proved. Compared with some known algorithms, numerical experiment not only demonstrates the higher computational efficiency of the proposed algorithm but also proves that the proposed algorithm is an efficient approach to solve the problems of path planning for the mobile robot.
The effect of multimedia-based nursing visit on preoperative anxiety and vital signs in patients undergoing lumbar disc herniation surgery: A randomised clinical trial
Authors: Zarei Behrooz , Valiee Sina , Nouri Bijan , Khosravi Fatemeh , Fathi Mohammad
Published: January 2018

This study was a randomised clinical trial on 60 candidates undergoing lumbar disc herniation surgery. Anxiety rate and vital signs were measured before and after the intervention. There was a statistically significant difference between the two groups in terms of the preoperative anxiety, systolic and diastolic blood pressure, pulse and respiratory rate (P = 0.0001). Neurosurgery perioperative nurses can make use of multimedia in preoperative nursing visit based on the needs of patients.
Effect of Vertical or Beveled Chondral Defect Creation on Rim Deformation and Contact
Authors: Yanke Adam B. , Konopka Megan L. , Butty Davietta C. , Meyer Maximilian A. , Cotter Eric J. , Espinoza Alejandro A. , Cole Brian J.
Published: January 2018

Objective

To determine biomechanical effects of knee cartilage defect perimeter morphology based on cartilage strain and opposing subchondral bone contact.

Design

Articular cartilage defects were created in 5 bovine femoral condyles: group 1, 45° inner bevel with 8-mm rim; group 2, vertical with 8-mm rim; and group 3, 45° outer bevel with 8-mm base. Samples were placed into a custom-machined micro–computed tomography tube and subjected to 800 N of axial loading. DICOM data were used to calculate cartilage thickness 4 and 6 mm from the center, distance between tibial cartilage surface and femoral subchondral bone, and contact width between tibial cartilage and subchondral bone. Strain 4 mm from the center and both absolute and change in distance (mm) to subchondral bone were compared between groups 1 and 2 using paired t tests. Strain at 6 mm and distance changed, loaded distance, and contact width (mm) were compared between groups using the Friedman test with post hoc analysis using Wilcoxon signed rank test.

Results

No significant differences in rim strain were noted between groups 1 and 2 at 4 mm ( P = 0.10) and between groups 1, 2, and 3 at 6 mm ( P = 0.247) from the defect center. The loaded distance was significantly different between groups 1 and 3 ( P = 0.013). No significant change in distance to the subchondral bone was found between groups ( P = 0.156). The difference in subchondral bone contact area approached but did not reach significance ( P = 0.074).

Conclusion

When debriding focal articular cartilage defects, establishment of an inner bevel decreases tissue deformation and contact with opposing subchondral bone.
An update on the safety of current therapies for Alzheimer’s disease: focus on rivastigmine
Authors: Khoury Rita , Rajamanickam Jayashree , Grossberg George T.
Published: January 2018

Alzheimer’s disease (AD) is the most common cause of major neurocognitive disorders worldwide. Despite all research efforts, therapeutic options for AD are still limited to two drug classes: cholinesterase inhibitors (ChEIs) and the NMDA-receptor antagonist memantine. Donepezil, rivastigmine and galantamine are the three ChEIs FDA-approved as first-line treatment for AD. Although they share the same mode of action, they differ in terms of their pharmacologic characteristics and route of administration, which can impact their safety and tolerability profile. Rivastigmine, available in both oral and transdermal patch formulations, is a slowly reversible dual inhibitor of acetyl and butyryl cholinesterase, selective for the G1 isoform of acetylcholinesterase, without hepatic metabolism by the CYP-450 system. Despite its unique features, it has been associated with a higher incidence of adverse events in comparison to other ChEIs. The oral form, approved for the treatment of mild to moderate AD, is associated with a higher incidence of gastrointestinal side effects. The transdermal patch formulation approved for use across all stages of AD has been shown to have a better tolerability profile in comparison to both the oral form and even other ChEIs. One important tolerability concern is adverse dermatologic reactions, which are mostly benign, and can be either preventable or manageable. One important safety concern is the risk of treatment overdose by administering multiple patches at the same time, potentially leading to fatal outcomes. This can be prevented by educating patients and caregivers about the proper use of the patch. The goal for the future would be to optimize the patch formulation to increase both efficacy and safety.
The smartphone as a snapshot of its use: Mobile media elicitation in qualitative interviews
Authors: Kaufmann Katja
Published: January 2018

Smartphones are increasingly used to advance mobile media methods. The devices’ capabilities to automatically log behavioural data as well as the integration of this log data into qualitative interviews for elicitation purposes promise increased validity. The paper argues that despite recent efforts in mixed methods, the methodological potential of the personalized user interfaces of smartphones has been overlooked. As these smartphone interfaces are the result of continuous personalization processes, they can be seen as snapshots of the phone’s current use. Thus, this form of data should have strong explanatory powers for understanding the related mobile media practices. The paper discusses the implications of this interface-based approach with two example studies where smartphone interfaces were integrated into qualitative interviews. It concludes that the approach is a useful addition to existing mobile media methods and enforces the notion that researchers need to discover new forms of data.
Prognostic value of histological activity in patients with ulcerative colitis in deep remission: A prospective multicenter study
Authors: Lobatón Triana , Bessissow Talat , Ruiz-Cerulla Alexandra , De Hertogh Gert , Bisschops Raf , Guardiola Jordi , Van Assche Gert , Vermeire Severine , Ferrante Marc
Published: January 2018

Background

Histological remission has been proposed as a new treatment goal in patients with ulcerative colitis (UC) although no universal definition for microscopic activity exists.

Aim

We evaluated the accuracy of histological activity to predict clinical relapse in UC patients with both clinical and endoscopic remission.

Methods

Asymptomatic UC patients in endoscopic remission (Mayo endoscopic sub‐score 0 or 1) undergoing surveillance colonoscopy in two referral hospitals were prospectively recruited. All colonic biopsies were analyzed according to the Geboes’ score (GS) and the presence of basal plasmacytosis (BP).

Results

Ninety‐six patients were included (38% women, median (interquartile range) age 50.0 (39.0–58.5) years, median disease duration 12.0 (6.5–19.5) years). Histological activity defined as GS ≥ 2B.1, GS ≥ 3.1, or BP was present in, respectively, 26%, 23% and 12%. Within 12 months from index endoscopy, 23% of the patients presented with clinical relapse. In multivariate analysis, active histological disease was the only risk factor predicting clinical relapse (odds ratio (95% confidence interval) 4.29 (1.55–11.87); p = 0.005 for GS ≥ 2B.1 and 4.31 (1.52–12.21); p = 0.006 for GS ≥ 3.1).

Conclusions

In patients with UC in clinical and endoscopic remission, histological activity is an independent risk factor for clinical relapse. Further prospective studies need to clarify whether treatment optimization is justified in this context.
Unleashing the tiger – iatrogenic autoimmunity from cancer immunotherapy drugs
Authors: Luu Queenie , Major Gabor
Published: January 2018

Immune checkpoint inhibitors can lead to the development of organ and non-organ specific immune related adverse events.
Beyond the Dopamine Hypothesis
Authors: Reynolds G. P.
Published: January 2018

The dopamine hypothesis still provides a valuable approach to the study of schizophrenia and its treatment by drugs. Although the neuroleptic drugs appear to act via an inhibition of dopamine receptors, measurements of dopamine metabolites in vivo, or of the transmitter and its receptors in postmortem brain tissue, do not provide unequivocal evidence of a hyperactivity of dopaminergic neurotransmission in the disease. Nevertheless, increased dopamine function might be a consequence of a primary neuronal abnormality in another system. Recent imaging studies and neuropathological reports suggest that, in some patients, there may be a deficit and/or disturbance of neurons in certain temporal limbic regions, and this is supported by some neurochemical investigations, particularly of neuropeptide and amino-acid transmitter systems. A loss of such neurons could conceivably lead to a disinhibition of limbic dopamine neurons, providing the means whereby neuroleptic drug treatment might ameliorate the effects of a neuronal deficit in schizophrenia.
Socio-Cultural Parameters in Yoruba Nigerian Patients with Affective Disorders
Authors: Makanjuola Roger O. A.
Published: January 2018

One hundred and ten consecutive new patients presenting with major affective disorders were divided into five categories according to pattern of presentation: recurrent manic disorder, recurrent depressive disorder, bipolar disorder, single episodes of manic disorder, and single episodes of major depressive disorder. Manic patients predominated, and recurrent manic disorder was much more frequent than either recurrent depressive or bipolar disorder. The manic and bipolar patients were younger. Females predominanted in all five groups of patients. The two manic groups were less likely to be married, but this was probably a reflection of their younger age. No differences were demonstrated with regard to educational status or occupation. There were no significant differences with regard to sibship position, family size, or polygamous/monogamous parents. Manic patients were more likely to have suffered permanent separation from one or both parents before the age of 12 years. A relatively low proportion of the patients had a positive history of mental disorder among first- or second-degree relatives. Manic and bipolar patients tended to present in hospital relatively early in their illness.
Routine outcome measurement: recovery, quality of life and co-production
Authors: Boardman Jed
Published: January 2018

Patient-reported outcome measures (PROMs) are self-rated, but may not take in other aspects of the patient's perspective, such as the inclusion of domains that reflect service-user priorities. The clinician's view still has priority, although this situation has shifted in recent years. The Recovering Quality of Life (ReQoL) offers an advance in this area.

Declaration of interest

None.
Senior house officer training in child and adolescent psychiatry
Authors: Bamforth Margaret , Morris Tim , Clarke Judith
Published: January 2018

As educators, we are being encouraged to use adult learning theory when organising training. This paper describes the development of a course originally for trainees in psychiatry and the shift from a traditional model of training to one that incorporates new approaches to learning (Spencer & Jordan, 1999). We describe the move away from a didactic delivery of information to a multiprofessional, skills-based approach to the training of general psychiatric trainees.
Books Reconsidered:Suicide, A Study in Sociology:Emile Durkheim
Authors: Symonds R. L.
Published: January 2018

Everyone has heard ofLe Suicide,by Emile Durkheim, but relatively few have read even its English translation. This is a pity, since it is a good read, although it may seem tasteless to enjoy a treatise on such a sad subject. French psychiatric literature has so lacked appeal for the English, that its first appearance in 1897 was not followed by an English translation until 1952. However, the English translation is vigorous, clear and vivid, capturing the spirit of the time of the original edition, an age away from the pompous and turgid sociological literature of today. Durkheim wrote the book, one of his two great works, using a social phenomenon – suicide –to investigate society itself. Psychiatrists might readSuicidefor the breadth and depth of its social data, now of historical interest, and for his closely reasoned sociological arguments.
Political Violence and the Health Professional
Authors: Turner Stuart
Published: January 2018

Andre Koppers is a historian, now working as a research assistant attached to the International Association on the Political Use of Psychiatry. His A Biographical Dictionary on the Political Abuse of Psychiatry in the USSR is published by the IAPUP, Amsterdam (£5, 180 pp., 1990) Lone Jacobsen is head nurse and Peter Vesti a psychiatrist at the Danish Rehabilitation and Research Centre for Torture Victims. Torture Survivors–A New Group of Patients is published by the Danish Nurses1 Organization, Amsterdam (£12, 80 pp., 1990, in an English translation by Bente Bach) and is intended primarily for nurses. Finally, Eric Stover, a staff officer with the American Association for the Advancement of Science (AAAS), and Elena Nightingale, lecturer in health policy at Harvard and chair of the AAAS Committee on Scientific Freedom and Responsibility, edited The Breaking of Bodies and Minds, published by W. H. Freeman, New York (£16.95 (pb), 335 pp., 1985).
Hunting the Muse
Authors: Jago Dave
Published: January 2018

Creativity and Madness: New Findings and Old Stereotypes, by Albert Rothenberg, is published by The Johns Hopkins University Press, Baltimore (£16.50, 199 pp., 1990). Professor Rothenberg is Clinical Professor of Psychiatry at Harvard University and Director of Research at the Austen Riggs Center in Stockbridge, Massachusetts. He is principal investigator for the project ‘Studies in the creativity process'.
Psychiatry: Evidence-Based but Still Value-Laden
Authors: Anderson Ian
Published: January 2018

The directive that we should be ‘for evidence-based medicine’ has the same moral imperative as Queen Elizabeth's affirmation that she is ‘against sin’. It seems impossible to take an opposing view without abandoning reason or at least ethics. And yet a feeling of uneasiness, or at least caution, stands in the way of wholehearted endorsement – why?
New Evidence is Required
Authors: Lewis Glyn
Published: January 2018

What's new about evidence-based medicine? Medical practice has been based upon scientific evidence for some time, although the standards of evidence we require before using a treatment are becoming more stringent. EBM places more emphasis on evidence from randomised controlled trials (RCTs) than on clinical anecdote, but the notion that RCTs are the best evidence on the effectiveness of interventions has been around for nearly SO years. There is more emphasis now on systematic reviews and although they are not a new idea, their widespread acceptance has been a relatively recent phenomenon within medicine.
The Doctor, His Patient and the Illness: Michael Balint
Authors: Pietroni Patrick C.
Published: January 2018

Remembering where you were when Jack Kennedy died has become a favourite question to ask of people of an age to remember that day in November 1963. For a certain generation of general practitioners, a not dissimilar question might be, “When did you first read The Doctor, His Patient and the Illness?” Balint's impact on general practice is remarkable and unquestioned. His book, first published in 1957, appears among the top ten, if not the top three, that all new entrants into general practice ‘must read’. Yet the paradox is that few, if any, trainees will actually read his book, that Balint groups have a falling membership, that the Balint Society, founded after his death by a group of GPs, is on the periphery of modern general practice thinking, and that few if any permanent developments have come from his followers. Balint might well be excused if he paraphrased the quote attributed to Jung, “Thank God I'm Balint and not a Balintian”.
Games People Play: the Psychology of Human Relationships: Eric Berne
Authors: Cramer Duncan
Published: January 2018

Games People Play is the second of four major books written by Berne describing his theory of psychotherapy, which is called transactional analysis. The other three are Transactional Analysis in Psychotherapy (1961), Principles of Group Treatment (1966), and What Do You Say After You Say Hello? (1972). Berne himself was an American psychiatrist, who although he was trained as a psychoanalyst was never accepted as one. Since his death in 1970, transactional analysis, or TA as it is colloquially called, has continued to flourish with its own organisation, the International Transactional Analysis Association, and quarterly periodical, the Transactional Analysis Journal. There is usually a chapter devoted to it in most textbooks of psychotherapy, such as Corsini's (1973) exemplary Current Psychotherapies. Consequently, it is important to bear in mind that this book is part of a corpus of ideas and of a movement that seems to be maintaining its influence. However, as a theory it appears as yet to have generated very little empirical research concerned with testing its underlying assumptions.
Commentary: Meta-analysis of trials comparing antidepressants with active placebos
Authors: Healy David
Published: January 2018

This attempt to establish treatment effect sizes follows a tradition, which dates back over 20 years, of assessing the effects of antidepressant treatment under ‘blinder conditions'. The method adopted by Moncrieff et al has some merit but involves a recourse to studies, many of which are over 30 years old. While the studies may not be seriously flawed, it is difficult to have much confidence in them. None appears to have included what the authors describe as an ‘inert’ placebo, which strictly speaking would be a non-drug arm to the study. The number of studies is small. The dose of drugs used, which might be expected to have some influence on outcomes, is not mentioned. Finally, as experience with studies in obsessive-compulsive disorder indicates, treatment effect sizes can vary substantially from one decade to another –most probably because different individuals are recruited although all may apparently meet the same diagnostic criteria.
Training psychiatrists for work in the community
Authors: Littlejohns Carl S. , Wilkinson Greg , Murphy Elaine
Published: January 2018

Community psychiatry represents a major revision of psychiatric service provision, and although there is currently no consistent body of knowledge upon which training for community psychiatry can be based, in the near future most psychiatrists will be working to a greater extent in the community.
Inauguration of the Statue of the late
Authors: Charlesworth
Published: January 2018

The ceremony of the inauguration of the statue of the late lamented Dr. Charlesworth, senior physician of the Lincoln Lunatic Asylum, took place on the 12th of July last, in presence of a large assembly. When the statue, which stands in an area at the south-east corner of the asylum grounds, visible both to the patients and the public, was exposed to view, all present uncovered; and, after a moment's silence, a burst of applause followed. It consists of a full-length figure of the doctor, in a position in which he frequently appeared, having his right hand advanced a little, grasping a small scroll, and his left resting on his hip; his head is reclining to the left, and the expression of the countenance is exceedingly faithful, expressing that studious habit and decision of character for which he was so remarkable. The statue is 6 feet 6 inches in height, and stands upon a pedestal of Yorkshire granite of the same elevation. The attitude of the figure is natural and full of character, and from whatever quarter viewed the features are a striking resemblance. The material is most suitable to the peculiarity of our variable climate, the sculptor (T. Milnes, Esq.) having selected Sicilian marble, the statue being worked from a block weighing upwards of six tons. It is of the finest texture, a beautiful colour, and will long retain its freshness. The following inscription is on the pedestal:
Insanity and Demoniacal Possession
Authors: Oxon M. A.
Published: January 2018

Our attention as reviewers has been drawn to the above subject by two papers published in the Journal of Psychological Medicine, the one by the Rev. Joseph Souter, chaplain to the Essex County Asylum; the other by the Rev. J. May, chaplain to the Hanwell County Asylum.
Random Response Spectrum Analysis of Gravity Dam Classes: Simplified, Practical, and Fast Approach
Authors: Hariri-Ardebili Mohammad Amin , Saouma Victor E.
Published: January 2018

The seismic risk of concrete dams may be assessed using various numerical techniques, ranging from simplified methods to linear and nonlinear ones. Such methods should be combined with probabilistic concepts to account for the randomness in both demand and capacity. This paper proposes a random version of a simplified response spectrum method (involving equivalent static lateral forces [ESLFs]) for gravity dams by means of propagating uncertainties through the input parameters. Input parameter sensitivity is quantified and the extended procedure is explained step by step. Results are then generalized for the different dam classes. The impacts of sampling size and technique (i.e., pseudo-random and quasi-random) are also discussed. A time-based performance is evaluated and fragility curves are derived. This method may be used during the initial stages of a design process or safety analysis for existing dams.
Seismic Forces in Ancillary Components Supported on Piers and Wharves
Authors: Goel Rakesh K.
Published: January 2018

This paper presents a simple procedure to estimate seismic forces in ancillary components (secondary systems) supported on marine structures such as piers, wharves, and marine oil terminals (primary systems). Since many such marine structures can be idealized as single-degree-of-freedom (SDOF) systems, this study uses a simple linear-elastic model with two DOF, one representing the marine structure and the other representing the ancillary component. This study shows that acceleration at the base of the secondary system is approximately equal to spectral acceleration at the fundamental period of the primary system. It also proposes a formula, which is an improvement over current ASCE 7-10 recommendations, to estimate acceleration amplification in the secondary system due to its flexibility when mass and period ratios of the secondary and primary systems are known. The procedure in this paper is strictly applicable to marine structures for which primarily a single mode contributes to seismic response.
mTOR signaling in stem and progenitor cells
Authors: Meng Delong , Frank Anderson R. , Jewell Jenna L.
Published: January 2018

The mammalian target of rapamycin (mTOR) senses nutrients and growth factors to coordinate cell growth, metabolism and autophagy. Extensive research has mapped the signaling pathways regulated by mTOR that are involved in human diseases, such as cancer, and in diabetes and ageing. Recently, however, new studies have demonstrated important roles for mTOR in promoting the differentiation of adult stem cells, driving the growth and proliferation of stem and progenitor cells, and dictating the differentiation program of multipotent stem cell populations. Here, we review these advances, providing an overview of mTOR signaling and its role in murine and human stem and progenitor cells.
Revealing age-related changes of adult hippocampal neurogenesis using mathematical models
Authors: Ziebell Frederik , Dehler Sascha , Martin-Villalba Ana , Marciniak-Czochra Anna
Published: January 2018

New neurons are continuously generated in the dentate gyrus of the adult hippocampus. This continuous supply of newborn neurons is important to modulate cognitive functions. Yet the number of newborn neurons declines with age. Increasing Wnt activity upon loss of dickkopf 1 can counteract both the decline of newborn neurons and the age-related cognitive decline. However, the precise cellular changes underlying the age-related decline or its rescue are fundamentally not understood. The present study combines a mathematical model and experimental data to address features controlling neural stem cell (NSC) dynamics. We show that available experimental data fit a model in which quiescent NSCs may either become activated to divide or may undergo depletion events, such as astrocytic transformation and apoptosis. Additionally, we demonstrate that old NSCs remain quiescent longer and have a higher probability of becoming re-activated than depleted. Finally, our model explains that high NSC-Wnt activity leads to longer time in quiescence while enhancing the probability of activation. Altogether, our study shows that modulation of the quiescent state is crucial to regulate the pool of stem cells throughout the life of an animal.
Cytoplasmic polyadenylation-mediated translational control of maternal mRNAs directs maternal-to-zygotic transition
Authors: Winata Cecilia Lanny , Łapiński Maciej , Pryszcz Leszek , Vaz Candida , bin Ismail Muhammad Hisyam , Nama Srikanth , Hajan Hajira Shreen , Lee Serene Gek Ping , Korzh Vladimir , Sampath Prabha , Tanavde Vivek , Mathavan Sinnakaruppan
Published: January 2018

In the earliest stages of animal development following fertilization, maternally deposited mRNAs direct biological processes to the point of zygotic genome activation (ZGA). These maternal mRNAs undergo cytoplasmic polyadenylation (CPA), suggesting translational control of their activation. To elucidate the biological role of CPA during embryogenesis, we performed genome-wide polysome profiling at several stages of zebrafish development. Our analysis revealed a correlation between CPA and polysome-association dynamics, demonstrating a coupling of translation to the CPA of maternal mRNAs. Pan-embryonic CPA inhibition disrupted the maternal-to-zygotic transition (MZT), causing a failure of developmental progression beyond the mid-blastula transition and changes in global gene expression that indicated a failure of ZGA and maternal mRNA clearance. Among the genes that were differentially expressed were those encoding chromatin modifiers and key transcription factors involved in ZGA, including nanog, pou5f3 and sox19b, which have distinct CPA dynamics. Our results establish the necessity of CPA for ensuring progression of the MZT. The RNA-seq data generated in this study represent a valuable zebrafish resource for the discovery of novel elements of the early embryonic transcriptome.
Glucose deprivation induces primary cilium formation through mTORC1 inactivation
Authors: Takahashi Kengo , Nagai Tomoaki , Chiba Shuhei , Nakayama Keiko , Mizuno Kensaku
Published: January 2018

Primary cilia are antenna-like sensory organelles extending from the surface of many cell types that play critical roles in tissue development and homeostasis. Here, we examined the effect of nutrient status on primary cilium formation. Glucose deprivation significantly increased the number of ciliated cells under both serum-fed and -starved conditions. Glucose deprivation-induced ciliogenesis was suppressed by overexpression of Rheb, an activator of the mammalian target of rapamycin complex-1 (mTORC1). Inactivating mTORC1 by rapamycin treatment or Raptor knockdown significantly promoted ciliogenesis. These results indicate that glucose deprivation promotes primary cilium formation through mTORC1 inactivation. Rapamycin treatment did not promote autophagy or degradation of OFD1, a negative regulator of ciliogenesis. In contrast, rapamycin treatment increased the level of the p27KIP1 (also known as CDKN1B) cyclin-dependent kinase inhibitor, and rapamycin-induced ciliogenesis was abrogated in p27KIP1-depleted cells. These results indicate that mTORC1 inactivation induces ciliogenesis through p27KIP1 upregulation, but not through autophagy. By contrast, glucose deprivation or rapamycin treatment shortened the cilium length. Thus, glucose deprivation and subsequent inactivation of mTORC1 play dual roles in ciliogenesis: triggering primary cilium formation and shortening cilium length.

This article has an associated First Person interview with the first author of the paper.
Meeting report – shining light on septins
Authors: Caudron Fabrice , Yadav Smita
Published: January 2018

Septins are enigmatic proteins; they bind GTP and assemble together like molecular Lego blocks to form intracellular structures of varied shapes such as filaments, rings and gauzes. To shine light on the biological mysteries of septin proteins, leading experts in the field came together for the European Molecular Biology Organization (EMBO) workshop held from 8–11 October 2017 in Berlin. Organized by Helge Ewers (Freie Universität, Berlin, Germany) and Serge Mostowy (Imperial College, London, UK), the workshop convened at the Harnack-Haus, a historic hub of scientific discourse run by the Max Planck Society.
Filamentous Viruses as Building Blocks for Hierarchical Self-Assembly toward Functional Soft Materials
Authors: Sawada Toshiki , Serizawa Takeshi
Published: January 2018

This review describes the utilization of M13 phage, one of the filamentous viruses, for the development of novel functional soft materials. Traditionally, M13 phage has been widely used as a scaffold to display peptides or proteins on the surface of M13 phage through genetic engineering. This technology is well known as “phage display”, and generally used nowadays for the construction of peptide or protein libraries on M13 phage surfaces to identify peptides or proteins with desired functions. Recently, construction of hierarchical assembled structures composed of M13 phage as a building block has generated great interest as a means of using the excellent properties of M13 phage for the development of novel classes of soft materials. In this case, liquid crystalline formation of M13 phage is effectively used to fabricate structurally regulated assemblies. Further combination of the phage display technique and liquid crystalline formation widely expands the applicability of M13 phage to various fields such as devices, sensors, and biomedicines. Such approaches to M13 phage should contribute to novel attractive opportunities for next-generation soft materials for science and technology.
Investigation of the use of external aluminium targets for portal imaging in a medical accelerator using Geant4 Monte Carlo simulation
Authors: Kim Hyungdong , Kim Byungyong , Baek Jonggeun , Oh Youngkee , Yun Sangmo , Jang Hyunsoo
Published: January 2018

Objective:

To install a low-Z target on the wedge tray mount of a medical linear accelerator to create a new image beam and to confirm image contrast enhancement.

Methods:

Experimental low-energy photon beams were produced with the linac running in the 6 MeV electron mode and with a low-Z target installed on the wedge tray mount [denoted 6 MeV (low-Z target)]. Geant4 Monte Carlo simulation was performed to analyse the energy spectrum and image contrast of a 6 MeV (low-Z target) beam. This study modelled the 6 MeV (low-Z target) beam and the 6 MV (megavoltage) radiotherapy photon beam and verified model validity by measurement. In addition, a contrast phantom was modelled to quantitatively compare the image contrasts of the 6 MeV (low-Z target) beam and the 6 MV radiotherapy photon beam. A low-Z target was fabricated to generate low-energy photons (25–150 keV) from incident electrons, and a portal image of the Alderson RANDO phantom was acquired using a clinical linear accelerator for qualitative analysis.

Results:

The measured and calculated percentage depth dose of the 6 MV photon and 6 MeV (Al) beams were consistent within 1.5 and 1.6%, respectively, and calculated lateral profiles of the 6 MV photon beam and the 6 MeV (Al) beam were consistent with the measured results within 1.5 and 1.9%, respectively. Although low-energy photons (25–150 keV) of the 6 MV photon beam were only 0.3%, the Be, C, and Al low-Z targets, but not the Ti target, generated 34.4 to 38.5% low-energy photons. In 5 to 20 cm water phantoms, contrast of the 6 MeV (Al) beam was approximately 1.16 times greater than that of the 6 MV beam. The contrasts of 6 MeV (Al) and 6 MV photon beams in the 20 cm water phantom were ~34% lower than those in the 5 cm water phantom. 6 MeV (Al)/CR (computed radiography) images of the human body phantom were more vivid and detailed than 6 MV/EPID (electronic portal imaging device) and 6 MeV (Al)/EPID images.

Conclusion:

The experimental beam with a low-Z target, which was simply installed on the wedge tray mount of the radiotherapy linear accelerator, generated significantly more low-energy photons than the 6 MV radiotherapy photon beam, and provided better quality portal images.

Advances in knowledge:

This study shows that, unlike the existing low-Z beam studies, a low-Z target can be installed outside the head of a linear accelerator to improve portal image quality.
Οι έμφυλες κατασκευές των παιδιών νηπιαγωγείου για τα επαγγέλματα
Authors: Παπαναστασίου Έμη
Published: January 2018

Το περιβάλλον των παιδιών τους προσφέρει πολλές πληροφορίες και γνώσεις σε σχέση με τα φύλα και τα επαγγέλματα, οι οποίες εκφράζονται με διάφορους τρόπους. Η έρευνα που παρουσιάζεται στο παρόν άρθρο περιγράφει τις αντιλήψεις/κατασκευές παιδιών νηπιαγωγείου σε σχέση με το επάγγελμα που θα ήθελαν να ακολουθήσουν αλλά και με τα επαγγέλματα που «αρμόζουν» στο κάθε φύλο. Η έρευνα πραγματοποιήθηκε με τη μέθοδο των ημι-δομημένων συνεντεύξεων που αναλύθηκαν υπό το θεωρητικό πρίσμα της φεμινιστικής κοινωνικής κατασκευής. Τα ευρήματα δείχνουν ότι τα παιδιά βασίζονται κυρίως σε δυιστικές στερεοτυπικές αντιλήψεις για τα φύλα και την επιλογή επαγγέλματος.
Does evidence support the high expectations placed in precision medicine? A bibliographic review
Authors: Cortés Jordi , González José Antonio , Medina María Nuncia , Vogler Markus , Vilaró Marta , Elmore Matt , Senn Stephen John , Campbell Michael , Cobo Erik
Published: January 2018

Background: Precision medicine is the Holy Grail of interventions that are tailored to a patient’s individual characteristics. However, the conventional design of randomized trials assumes that each individual benefits by the same amount.

Methods: We reviewed parallel trials with quantitative outcomes published in 2004, 2007, 2010 and 2013. We collected baseline and final standard deviations of the main outcome. We assessed homoscedasticity by comparing the outcome variability between treated and control arms.

Results: The review provided 208 articles with enough information to conduct the analysis. At the end of the study, 113 (54%, 95% CI 47 to 61%) papers find less variability in the treated arm. The adjusted point estimate of the mean ratio (treated to control group) of the outcome variances is 0.89 (95% CI 0.81 to 0.97).

Conclusions: Some variance inflation was observed in just 1 out of 6 interventions, suggesting the need for further eligibility criteria to tailor precision medicine. Surprisingly, the variance was more often smaller in the intervention group, suggesting, if anything, a reduced role for precision medicine.  Homoscedasticity is a useful tool for assessing whether or not the premise of constant effect is reasonable.