bluuebunny/crossref_metadata_2025 huggingface dataset:
Constructive Alignment in the Field of Educational Psychology: Development and Application of a Questionnaire for Assessing Constructive Alignment
Authors: Deibl Ines , Zumbach Jörg , Geiger Viola M. , Neuner Christine M.
Published: August 2018

Teaching of Psychology includes a great variety of topics, course formats, and assessment approaches. A central concept that incorporated the interface between teaching goals, instructional methods, and examination modalities is referred to as Constructive Alignment (CA). This model addresses possible designs of teaching to improve students’ learning outcomes as well as enhance their learning experiences, and claims to be applicable independent of disciplinary culture or content. Despite the importance of this approach from an instructional point of view, there is hardly any research, so far, that has been concerned with capturing the three dimensions of CA. As a consequence, the aim of our study was to create an instrument to assess the quality of CA within psychology classes. A questionnaire was designed and was additionally analyzed with regard to students’ judgements about overall course evaluation. The questionnaire was employed in two lectures within the field of educational psychology for teacher training students. Results reveal that overall course evaluation can be predicted by the match between course objectives and instructional methods whereas other course evaluation factors failed as predictors. With a high internal consistency, the instrument provides an alternative or a supplement for traditional course evaluation instruments.
Diabetes, subclinical atherosclerosis and multiple cardiovascular risk factors in hard-to-reach asymptomatic patients
Authors: Mamudu Hadii M , Alamian Arsham , Paul Timir , Subedi Pooja , Wang Liang , Jones Antwan , Alamin Ali E , Stewart David , Blackwell Gerald , Budoff Matthew
Published: August 2018

Aim:

To examine the association of cardiovascular disease risk factors with and their cumulative effect on coronary artery calcium in hard-to-reach asymptomatic patients with diabetes.

Methods:

A total of 2563 community-dwelling asymptomatic subjects from Central Appalachia participated in coronary artery calcium screening at a heart centre. Binary variable was used to indicate that coronary artery calcium was either present or absent. Independent variables consisted of demographic and modifiable risk factors and medical conditions. Descriptive statistics and multinomial logistic regression analyses were conducted.

Results:

In total, 55.8% and 13.7% of study participants had subclinical atherosclerosis (coronary artery calcium ⩾1) and diabetes, respectively. The presence of coronary artery calcium was higher in subjects with diabetes (68.5%) than those without (53.8%). Compared to subjects without diabetes with coronary artery calcium = 0, obesity, hypertension, hypercholesterolaemia and smoking increased the odds of the presence of coronary artery calcium (coronary artery calcium score ⩾1) regardless of diabetes status; however, with larger odds ratios in subjects with diabetes. Compared to subjects without diabetes with coronary artery calcium score = 0, having 3, 4 and ⩾5 risk factors increased the odds of presence of coronary artery calcium in subjects with diabetes by 14.06 (confidence interval = 3.26–62.69), 32.30 (confidence interval = 7.41–140.82) and 47.12 (confidence interval = 10.35–214.66) times, respectively.

Conclusion:

There is a need for awareness about subclinical atherosclerosis in patients with diabetes and more research about coronary artery calcium in subpopulations of patients.
Industrial Conceptualization of Health Care Versus the Naturalistic Decision-Making Paradigm: Work as Imagined Versus Work as Done
Authors: Catchpole Ken , Alfred Myrtede
Published: August 2018

Quality and safety concerns in health care over the past 20 years precipitated the need to move beyond the traditional view of health care as an artisanal process toward a sociotechnical systems view of performance. The adoption of industrial approaches placed a greater emphasis on standardization of processes and outcomes, often treating humans as the “weak” part of the system rather than valuing their role in holding together complex, opaque, and unpredictable clinical systems. Although some health care tasks can be modeled linearly, others are much more complex. Efforts to reduce variation in clinical reasoning through evidence-based practices have proven problematic by failing to provide a means for context-specific adaptation or to account for the complex and adaptive nature of clinical work. We argue that the current, highly empirical approach to clinical decision making reflects clinical reasoning “as imagined,” whereas the application of the naturalistic decision-making (NDM) paradigm can help reveal clinical reasoning “as done.” This approach will have benefits for improving the conditions for diagnosis; the design of acute, time-pressured clinical work; the identification of deteriorating patients; the development of clinical decision support systems; and many more clinical tasks. Health care seems ready to accept NDM approaches.
Three Observations
Authors: Beach Lee Roy
Published: August 2018

Invited commentary on “Naturalistic Decision Making and the Practice of Health Care,” by Paul R. Falzer for the Journal of Cognitive Engineering and Decision Making.
Reimagining the Humble but Mighty Pen: Quality Measurement and Naturalistic Decision Making
Authors: Schneider Eric C.
Published: August 2018

Much of the health system’s avoidable spending may be driven by doctors’ decision making. Past studies demonstrated potentially consequential and costly inconsistencies between the actual decisions that clinicians make in daily practice and optimal evidence-based decisions. This commentary examines the “best practices regimen” through the lens of the quality measurement movement.  Although quality measures have proliferated via public reporting and pay-for-performance programs, evidence for their impact on quality of care is scant; the cost of care has continued to rise; and the environment for clinical decisions may not have improved. Naturalistic decision making offers a compelling alternative conceptual frame for quality measurement. An alternative quality measurement system could build on insights from naturalistic decision making to optimize doctors’ and patients’ joint decisions, improve patients’ health outcomes, and perhaps slow the growth of health care spending in the future.
Evidence-Based Medicine, Best Practices, Transductive Models, and Naturalistic Decision Making: Commentary on Paul R. Falzer, Naturalistic Decision Making and the Practice of Health Care
Authors: Haynes Robert Brian
Published: August 2018

Expert and informed decision making is an essential process in all of health care. Evidence-Based Medicine (EBM) purports to support and enhance this process by the timely infusion of high-quality, pertinent evidence from health research, tailored as closely as possible to the individual and their health problem. Doing so is not an easy task for many reasons, beginning with imperfections and incompleteness in the evidence and ending with the complexities of the dual decision making required by individuals and their care providers. EBM needs a lot of help supporting decision-making processes and welcomes further interdisciplinary collaboration. The “conformist principle,” “best practice regimens,” and “transductive models” should not be considered as barriers to such collaboration: These are not part of EBM. Rather, EBM has always seen evidence from health research as but one of many inputs to decision making by providers and patients. An overarching problem for collaboration to address is understanding the decision-making process well enough to develop effective means to bolster it, so that people are consistently offered the current best options for their problems in a way that fits their circumstances and that they can understand and judge.
Impact of Low-Dose Occupational Exposure to Ionizing Radiation on T-Cell Populations and Subpopulations and Humoral Factors Included in the Immune Response
Authors: Gyuleva Ilona , Djounova Jana , Rupova Ivanka
Published: August 2018

The aim of the present study is to assess the effects of low-dose occupational exposure on T helper response. One Hundred five employees working in Nuclear Power Plant, Kozloduy, Bulgaria and control group of 32 persons are included in this investigation. Flow cytometry measurements of T-cell populations and subpopulations and natural killer T cells are performed and levels of G, A, and M immunoglobulins and interleukin 2 (IL-2), IL-4, and interferon γ were determined. The data interpreted with regard to cumulative doses, length of service, and age. The results of the present study are not enough to outline a clear impact of occupational radiation exposure on T helper populations. Nevertheless, the observed even slight trends in some lymphocyte’s populations and in cytokines profile give us the reason to assume a possibility of a gradual polarization of T helper 1 to T helper 2 immune response at dose range 100 to 200 mSv. The results of the present study indicate the need to perform a more detailed epidemiological survey including potential confounding and misclassifying factors and possible selection bias that could influence the results.
Pressure sensitivity of multiscale carbon-admixtures–enhanced cement-based composites
Authors: Hong Yi , Li Zuohua , Qiao Guofu , Ou Jinping , Cheng Wei
Published: August 2018

The pressure-sensitive cement-based composites added with multiscale carbon materials, that is, carbon blacks, carbon fibers, and carbon nanotubes are investigated. In the article, the sensing property of cement-based composites with seven different proportions of carbon blacks, carbon fibers, and carbon nanotubes under cyclic loading is discussed and then the optimized formula among these seven proportions is chosen to investigate the influences of temperature and saturation degree on its sensing properties. In addition, the maximum perceivable frequency of multiscale carbon-admixtures–enhanced cement-based composite is obtained from the experimental results. The results indicate that the fractional change in resistance of the cement-based sensing composites increases at first and then decreases with the increase of temperature, but decreases with the increase of humidity. Additionally, the fractional change in resistance has a decrease with the increase of loading frequency, and the cement-based sensing composites prepared can perceive the biggest loading frequency of 0.5 Hz.
Prognosis of Chronic Rhinosinusitis With Nasal Polyps Using Preoperative Eosinophil/Basophil Levels and Treatment Compliance
Authors: Guo Michael , Alasousi Fahad , Okpaleke Christopher , Habib Al-Rahim , Javer Amin
Published: August 2018

Background

Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have a high risk of disease recurrence and revision surgery. The ability to predict a polyp recurrence in this patient population is critical in order to provide adequately tailored postoperative management.

Objective

We aim to explore the role of appropriate postoperative care in the prognosis of CRSwNP patients in relation to preoperative eosinophil and basophils levels.

Methods

This was a retrospective case series; data were collected for 102 CRSwNP patients over a period of 15 months after surgery. Baseline eosinophil and basophil levels were compared between patients with and without polyp recurrences. The analysis was then stratified based on clinical diagnosis, comorbidities (atopy, asthma, and aspirin allergy), a single versus multiple episodes of sinonasal polyp recurrences, and medication adherence.

Results

Of the 102 included patients, 65 (63.7%) of the patients experienced no recurrences, 26 (25.5%) experienced a single episode of recurrence, and 11 (10.8%) experienced multiple recurrences. Mean baseline eosinophil count and percentage of total white blood cells were significantly higher in the multiple recurrences group (0.70 × 109/L and 10%) compared with the no recurrences group (0.36 × 109/L and 5%). Adherence to prescribed medical therapy prior to the first episode of recurrence was significantly lower for the single exacerbations group (42.3%) than the multiple recurrences group (88.9%).

Conclusions

Patients with multiple recurrences of nasal polyps had significantly higher baseline eosinophil counts and significantly higher medication adherence compared to single exacerbations of nasal polyps. Single exacerbations may not reflect true failures of surgery but rather a failure of postoperative medical care. Basophil levels were inadequate to predict polyp recurrence rates.
Effect of Endoscopic Sinus Surgery on Bronchiectasis Patients With Chronic Rhinosinusitis
Authors: Kanjanaumporn Jesada , Hwang Peter H.
Published: August 2018

Background

The concept of unified airway disease has linked bronchiectasis with chronic rhinosinusitis (CRS), much in the same way as in asthma and CRS. Although the outcomes of endoscopic sinus surgery (ESS) on comorbid asthma have been relatively well studied, the outcomes of ESS on comorbid bronchiectasis have rarely been examined.

Objective

We sought to determine sinonasal and pulmonary clinical outcomes of ESS in bronchiectasis patients with CRS.

Method

We reviewed all bronchiectasis patients who had ESS for CRS at our institution from 2006 to present. The sinonasal outcome test 22 (SNOT-22) was administered preoperatively and at 3 months, 1 year, and 3 years postoperatively. Pulmonary function tests (PFTs) were measured preoperatively and at 6 months and 1 year post operation to assess the forced expiratory volume in 1 s (FEV1), forced viral capacity (FVC), and FEV1/FVC values. Paired t test and Pearson correlation were used to compare pre- and postsurgical results.

Results

A total of 141 bronchiectasis patients who had ESS for CRS were studied. The most common cause of bronchiectasis was cystic fibrosis (CF) (42.55%). SNOT-22 scores improved at 3 months post operation and were maintained at 1 year and 3 years post operation ( P < .001). All SNOT sub-domains showed a significant improvement after surgery ( P < .01). However, PFTs did not change at 6 months post operation and 1 year post operation ( P > .05). There were significant differences in the outcomes in CF versus non-CF patients ( P < .05) but not by sex or age.

Conclusion

ESS is effective in improving long-term sinonasal outcomes in bronchiectasis patients with CRS. However, ESS does not appear to improve the pulmonary function.
Psychometric validation of the Carers of Older People in Europe Index among family caregivers of older persons with dementia
Authors: Moholt Jill-Marit , Friborg Oddgeir , Skaalvik Mari Wolff , Henriksen Nils
Published: August 2018

Objectives:

The Carers of Older People in Europe Index is a first-stage assessment tool to detect family caregivers in need of support. This instrument assesses caregivers’ subjective perceptions of their caregiving circumstances. The present study examines the psychometric properties of the Norwegian version of the Carers of Older People in Europe Index among family caregivers for older persons with dementia living at home.

Methods:

Cross-sectional survey data were collected from 430 dementia caregivers. The sample was randomly split as follows: the first half of the sample was used to identify the measurement model using an exploratory factor analysis, and the second half of the sample was used to cross-validate the model using a confirmatory factor analysis. The criterion validity and reliability (internal consistency and test–retest reliability) of the Carers of Older People in Europe Index were also examined.

Results:

Using an exploratory factor analysis, we extracted three factors that were consistent with previous findings: negative impact of caregiving, positive values of caregiving and quality of support. This model fit the data well using a confirmatory factor analysis. Moreover, a second-order model could replace the three-factor correlated model without sacrificing the model fit, supporting the use of a global impact of caregiving score. The three factors and the global factor correlated with the criteria measures in the expected directions. The internal consistency was assessed using Cronbach’s alpha and was good for the negative impact ( α = 0.86) and the quality of support ( α = 0.76) factors. The positive values factor was less consistent ( α = 0.64). The test–retest reliability was examined using Spearman’s rank order correlation and was good for all three factors.

Conclusion:

The psychometric properties of the Norwegian version of the Carers of Older People in Europe Index are good. The instrument assesses dementia caregivers’ situations across three primary factors or alternatively validly summarizes the factors in a global impact of caregiving score.
A Systematic Review of Classification Systems for Cervical Ossification of the Posterior Longitudinal Ligament
Authors: Tetreault Lindsay , Nakashima Hiroaki , Kato So , Kryshtalskyj Michael , Nagoshi Nagoshi , Nouri Aria , Singh Anoushka , Fehlings Michael G.
Published: August 2018

Design:

Systematic review.

Objective:

To conduct a systematic review to (1) summarize various classification systems used to describe cervical ossification of the posterior longitudinal ligament (OPLL) and (2) evaluate the diagnostic accuracy of various imaging modalities and the reliability of these classification systems.

Methods:

A search was performed to identify studies that used a classification system to categorize patients with OPLL. Furthermore, studies were included if they reported the diagnostic accuracy of various imaging modalities or the reliability of a classification system.

Results:

A total of 167 studies were deemed relevant. Five classification systems were developed based on X-ray: the 9-classification system (0.60%); continuous, segmental, mixed, localized or focal, circumscribed and others (92.81%); hook, staple, bridge, and total types (2.40%); distribution of OPLL (2.40%); and K-line classification (4.19%). Six methods were based on computed tomography scans: free-type, contiguous-type, and broken sign (0.60%); hill-, plateau-, square-, mushroom-, irregular-, or round-shaped (5.99%); rectangular, oval, triangular, or pedunculate (1.20%); centralized or laterally deviated (1.80%); plank-, spindle-, or rod-shaped (0.60%); and rule of nine (0.60%). Classification systems based on 3-dimensional computed tomography were bridging and nonbridging (1.20%) and flat, irregular, and localized (0.60%). A single classification system was based on magnetic resonance imaging: triangular, teardrop, or boomerang. Finally, a variation of methods was used to classify OPLL associated with the dura mater (4.19%).

Conclusions:

The most common method of classification was that proposed by the Japanese Ministry of Health, Labour and Welfare. Other important methods include K-line (+/−), signs of dural ossification, and patterns of distribution.
(Re)imagining Writers and Writing: The End of the Book and the Beginning of Writing
Authors: Kuby Candace R. , Fontanella-Nothom Oona
Published: August 2018

We think with several theoretical concepts from Jacques Derrida (defer, différance, deconstruction, and trace), in order to better understand how the processes of children, materials, and a teacher (re)defined and (re)imagined writing when they began to compose with a range of tools as writers in a second grade (7- to 8-year-olds) Writers’ Studio. We share two literacy desirings: (1) Cotton Ball Bird and (2) Paper Monsters. Thinking with Derrida’s theory is important, as it causes us to examine the processes of literacies coming into being, not solely the end products or artifacts of literacy nor simply a focus on knowledge or meaning-making. Derrida’s theory is about the now, the current realities and relationships produced and provides inspiration for how educators can work with children (and materials, time, and space) to create new ways of be(com)ing/doing/knowing literacies.
Safety of Ultrasound Exposure: Knowledge, Attitudes, and Practices of Australasian Sonographers
Authors: Moderiano Monique , McEvoy Maureen , Childs Jessie , Esterman Adrian
Published: August 2018

Introduction:

While perceived as safe, diagnostic ultrasound has the potential to cause biological effects on the body tissues. The aim of this study was to evaluate knowledge, attitudes, and practices of Australasian sonographers on bioeffects and safety of ultrasound scanning.

Methods:

Focus groups were used to develop a questionnaire to explore knowledge, attitudes, and practices of ultrasound safety, which was then distributed to Australasian sonographers. Thematic (focus groups) and descriptive (questionnaires) analyses were undertaken.

Results:

A 37-item questionnaire addressed knowledge, attitudes, and practices of ultrasound safety. In 47 collected responses, sonographers demonstrated good familiarity of thermal index (TI) (79%), mechanical index (MI) (68%), and “as low as reasonably achievable” (ALARA) principle (85%). However, most sonographers could not accurately define TI (13%) and had poor knowledge of safety guidelines relating to TI (19%) and MI (14%). Over 30% were uncertain about their attitudes to ultrasound safety issues. While 52% always and 30% most of the time adhere to ALARA, 37% of sonographers reported never monitoring TI and MI.

Discussion:

While familiar with safety terms, knowledge of safety guidelines was lacking. Many sonographers were uncertain about their attitudes to the safety of scans, and safety practices involving monitoring for bioeffects were not a high priority.
Extensively drug-resistant tuberculosis in South Africa: genomic evidence supporting transmission in communities
Authors: Auld Sara C. , Shah N. Sarita , Mathema Barun , Brown Tyler S. , Ismail Nazir , Omar Shaheed Vally , Brust James C.M. , Nelson Kristin N. , Allana Salim , Campbell Angela , Mlisana Koleka , Moodley Pravi , Gandhi Neel R.
Published: August 2018

Despite evidence that transmission is driving an extensively drug-resistant TB (XDR-TB) epidemic, our understanding of where and between whom transmission occurs is limited. We sought to determine whether there was genomic evidence of transmission between individuals without an epidemiologic connection.

We conducted a prospective study of XDR-TB patients in KwaZulu-Natal, South Africa, during the 2011–2014 period. We collected sociodemographic and clinical data, and identified epidemiologic links based on person-to-person or hospital-based connections. We performed whole-genome sequencing (WGS) on theMycobacterium tuberculosisisolates and determined pairwise single nucleotide polymorphism (SNP) differences.

Among 404 participants, 123 (30%) had person-to-person or hospital-based links, leaving 281 (70%) epidemiologically unlinked. The median SNP difference between participants with person-to-person and hospital-based links was 10 (interquartile range (IQR) 8–24) and 16 (IQR 10–23), respectively. The median SNP difference between unlinked participants and their closest genomic link was 5 (IQR 3–9) and half of unlinked participants were within 7 SNPs of at least five participants.

The majority of epidemiologically-unlinked XDR-TB patients had low pairwise SNP differences with at least one other participant, consistent with transmission. These data suggest that much of transmission may result from casual contact in community settings between individuals not known to one another.
RETRACTED ARTICLE: Inhibition of inflammation using diacerein markedly improved renal function in endotoxemic acute kidney injured mice
Authors: Yu Guangzhe , Liu Qian , Dong Xuening , Tang Kaihong , Li Bohui , Liu Chunmei , Zhang Wenzheng , Wang Yiduo , Jin Yingyu
Published: August 2018

Background

Inflammation is an important pathogenic component of endotoxemia-induced acute kidney injury (AKI), finally resulting in renal failure. Diacerein is an interleukin-1β (IL-1β) inhibitor used for osteoarthritis treatment by exerting anti-inflammatory effects. This study aims to investigate the effects of diacerein on endotoxemia-induced AKI.

Methods

Male C57BL/6 mice were intraperitoneally injected with lipopolysaccharide (LPS, 10 mg/kg) for 24 h prior to diacerein treatment (15 mg/kg/day) for another 48 h. Mice were examined by histological, molecular and biochemical approaches.

Results

LPS administration showed a time-dependent increase of IL-1β expression and secretion in kidney tissues. Diacerein treatment normalized urine volume and osmolarity, reduced blood urea nitrogen (BUN), fractional excretion of sodium (FENa), serum creatinine and osmolarity, and protected renal function in an endotoxemic AKI mice model. In the histopathologic study, diacerein also improved renal tubular damage such as necrosis of the tubular segment. Moreover, diacerein inhibited LPS-induced increase of inflammatory cytokines, such as IL-1β, tumor necrosis factor-α, monocyte chemoattractant protein-1 and nitric oxide synthase 2. In addition, LPS administration markedly decreased aquaporin 1 (AQP1), AQP2, AQP3, Na,K-ATPase α1, apical type 3 Na/H exchanger and Na-K-2Cl cotransporter expression in the kidney, which was reversed by diacerein treatment. We also found that diacerein or IL-1β inhibition prevented the secretion of inflammatory cytokines and the decrease of AQP and sodium transporter expression induced by LPS in HK-2 cells.

Conclusion

Our study demonstrates for the first time that diacerein improves renal function efficiently in endotoxemic AKI mice by suppressing inflammation and altering tubular water and sodium handing. These results suggest that diacerein may be a novel therapeutic agent for the treatment of endotoxemic AKI.
Assessment of demographic and perinatal predictors of non-response and impact of non-response on measures of association in a population-based case control study: findings from the Georgia Study to Explore Early Development
Authors: Schieve Laura A. , Harris Shericka , Maenner Matthew J. , Alexander Aimee , Dowling Nicole F.
Published: August 2018

Background

Participation in epidemiologic studies has declined, raising concerns about selection bias. While estimates derived from epidemiologic studies have been shown to be robust under a wide range of scenarios, additional empiric study is needed. The Georgia Study to Explore Early Development (GA SEED), a population-based case–control study of risk factors for autism spectrum disorder (ASD), provided an opportunity to explore factors associated with non-participation and potential impacts of non-participation on association studies.

Methods

GA SEED recruited preschool-aged children residing in metropolitan-Atlanta during 2007–2012. Children with ASD were identified from multiple schools and healthcare providers serving children with disabilities; children from the general population (POP) were randomly sampled from birth records. Recruitment was via mailed invitation letter with follow-up phone calls. Eligibility criteria included birth and current residence in study area and an English-speaking caregiver. Many children identified for potential inclusion could not be contacted. We used data from birth certificates to examine demographic and perinatal factors associated with participation in GA SEED and completion of the data collection protocol. We also compared ASD-risk factor associations for the final sample of children who completed the study with the initial sample of all likely ASD and POP children invited to potentially participate in the study, had they been eligible. Finally, we derived post-stratification sampling weights for participants who completed the study and compared weighted and unweighted associations between ASD and two factors collected via post-enrollment maternal interview: infertility and reproductive stoppage.

Results

Maternal age and education were independently associated with participation in the POP group. Maternal education was independently associated with participation in the ASD group. Numerous other demographic and perinatal factors were not associated with participation. Moreover, unadjusted and adjusted odds ratios for associations between ASD and several demographic and perinatal factors were similar between the final sample of study completers and the total invited sample. Odds ratios for associations between ASD and infertility and reproductive stoppage were also similar in unweighted and weighted analyses of the study completion sample.

Conclusions

These findings suggest that effect estimates from SEED risk factor analyses, particularly those of non-demographic factors, are likely robust.
Stigma experienced by family members of people with intellectual and developmental disabilities: multidimensional construct
Authors: Mitter Natasha , Ali Afia , Scior Katrina
Published: August 2018

Background

There is a lack of good-quality instruments measuring stigma experienced by family members of stigmatised people.

Aims

To develop a self-report measure of stigma among families of people with intellectual and developmental disabilities and examine associations between family stigma and other variables.

Method

The new Family Stigma Instrument (FAMSI) was tested with 407 family carers, 53% of whose offspring had an autism spectrum disorder in addition to intellectual disability. They also completed measures of subjective well-being, caregiver burden, self-esteem and social support.

Results

The FAMSI yielded a five-factor structure and had good reliability. Perceived family stigma, caregiver burden and subjective well-being were the strongest predictors of family stigma.

Conclusions

This instrument can advance our understanding of the impact of stigma on family members. It can also help us understand sociodemographic, psychosocial and contextual variables of both the carer and cared for person that may influence family members' experiences.

Declaration of interest

None.
Security of mind: 20 years of attachment theory and its relevance to psychiatry
Authors: Adshead Gwen
Published: August 2018

In this editorial, I suggest that no psychiatrist should be without a working knowledge of attachment theory, and it is a capability that all trainees should cover in the proposed new curriculum. I have focused on three domains of research to argue that attachment theory is relevant to practicing psychiatrists.

Declaration of interest

None.
Neurotrophins, cytokines, oxidative stress mediators and mood state in bipolar disorder: systematic review and meta-analyses
Authors: Rowland Tobias , Perry Benjamin I. , Upthegrove Rachel , Barnes Nicholas , Chatterjee Jayanta , Gallacher Daniel , Marwaha Steven
Published: August 2018

Background

A reliable biomarker signature for bipolar disorder sensitive to illness phase would be of considerable clinical benefit. Among circulating blood-derived markers there has been a significant amount of research into inflammatory markers, neurotrophins and oxidative stress markers.

Aims

To synthesise and interpret existing evidence of inflammatory markers, neurotrophins and oxidative stress markers in bipolar disorder focusing on the mood phase of illness.

Method

Following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines, a systematic review was conducted for studies investigating peripheral biomarkers in bipolar disorder compared with healthy controls. We searched Medline, Embase, PsycINFO, SciELO and Web of Science, and separated studies by bipolar mood phase (mania, depression and euthymia). Extracted data on each biomarker in separate mood phases were synthesised using random-effects model meta-analyses.

Results

In total, 53 studies were included, comprising 2467 cases and 2360 controls. Fourteen biomarkers were identified from meta-analyses of three or more studies. No biomarker differentiated mood phase in bipolar disorder individually. Biomarker meta-analyses suggest a combination of high-sensitivity C-reactive protein/interleukin-6, brain derived neurotrophic factor/tumour necrosis factor (TNF)-α and soluble TNF-α receptor 1 can differentiate specific mood phase in bipolar disorder. Several other biomarkers of interest were identified.

Conclusions

Combining biomarker results could differentiate individuals with bipolar disorder from healthy controls and indicate a specific mood-phase signature. Future research should seek to test these combinations of biomarkers in longitudinal studies.

Declaration of interest

None.
Frequency of Germline Mutations in Cancer Susceptibility Genes in Malignant Mesothelioma
Authors: Panou Vasiliki , Gadiraju Meghana , Wolin Arthur , Weipert Caroline M. , Skarda Emily , Husain Aliya N. , Patel Jyoti D. , Rose Buerkley , Zhang Shannon R. , Weatherly Madison , Nelakuditi Viswateja , Knight Johnson Amy , Helgeson Maria , Fischer David , Desai Arpita , Sulai Nanna , Ritterhouse Lauren , Røe Oluf D. , Turaga Kiran K. , Huo Dezheng , Segal Jeremy , Kadri Sabah , Li Zejuan , Kindler Hedy L. , Churpek Jane E.
Published: August 2018

Purpose

The aim of the current study was to determine the prevalence and clinical predictors of germline cancer susceptibility mutations in patients with malignant mesothelioma (MM).

Methods

We performed targeted capture and next-generation sequencing of 85 cancer susceptibility genes on germline DNA from 198 patients with pleural, peritoneal, and tunica vaginalis MM.

Results

Twenty-four germline mutations were identified in 13 genes in 23 (12%) of 198 patients. BAP1 mutations were the most common (n = 6; 25%). The remaining were in genes involved in DNA damage sensing and repair (n = 14), oxygen sensing (n = 2), endosome trafficking (n = 1), and cell growth (n = 1). Pleural site (odds ratio [OR], 0.23; 95% CI, 0.10 to 0.58; P < .01), asbestos exposure (OR, 0.28; 95% CI, 0.11 to 0.72; P < .01), and older age (OR, 0.95; 95% CI, 0.92 to 0.99; P = .01) were associated with decreased odds of carrying a germline mutation, whereas having a second cancer diagnosis (OR, 3.33; 95% CI, 1.22 to 9.07; P = .02) significantly increased the odds. The odds of carrying a mutation in BAP1 (OR, 1,658; 95% CI, 199 to 76,224; P < .001), BRCA2 (OR, 5; 95% CI, 1.0 to 14.7; P = .03), CDKN2A (OR, 53; 95% CI, 6 to 249; P < .001), TMEM127 (OR, 88; 95% CI, 1.7 to 1,105; P = .01), VHL (OR, 51; 95% CI, 1.1 to 453; P = .02), and WT1 (OR, 20; 95% CI, 0.5 to 135; P = .049) were significantly higher in MM cases than in a noncancer control population. Tumor sequencing identified mutations in a homologous recombination pathway gene in 52% (n = 29 of 54).

Conclusion

A significant proportion of patients with MM carry germline mutations in cancer susceptibility genes, especially those with peritoneal MM, minimal asbestos exposure, young age, and a second cancer diagnosis. These data support clinical germline genetic testing for patients with MM and provide a rationale for additional investigation of the homologous recombination pathway in MM.
Personalized Clinical Decision Making Through Implementation of a Molecular Tumor Board: A German Single-Center Experience
Authors: Hoefflin Rouven , Geißler Anna-Lena , Fritsch Ralph , Claus Rainer , Wehrle Julius , Metzger Patrick , Reiser Meike , Mehmed Leman , Fauth Lisa , Heiland Dieter Henrik , Erbes Thalia , Stock Friedrich , Csanadi Agnes , Miething Cornelius , Weddeling Britta , Meiss Frank , von Bubnoff Dagmar , Dierks Christine , Ge Isabell , Brass Volker , Heeg Steffen , Schäfer Henning , Boeker Martin , Rawluk Justyna , Botzenhart Elke Maria , Kayser Gian , Hettmer Simone , Busch Hauke , Peters Christoph , Werner Martin , Duyster Justus , Brummer Tilman , Boerries Melanie , Lassmann Silke , von Bubnoff Nikolas
Published: August 2018

Purpose

Dramatic advances in our understanding of the molecular pathophysiology of cancer, along with a rapidly expanding portfolio of molecular targeted drugs, have led to a paradigm shift toward personalized, biomarker-driven cancer treatment. Here, we report the 2-year experience of the Comprehensive Cancer Center Freiburg Molecular Tumor Board (MTB), one of the first interdisciplinary molecular tumor conferences established in Europe. The role of the MTB is to recommend personalized therapy for patients with cancer beyond standard-of-care treatment.

Methods

This retrospective case series includes 198 patients discussed from March 2015 through February 2017. The MTB guided individual molecular diagnostics, assessed evidence of actionability of molecular alterations, and provided therapy recommendations, including approved and off-label treatments as well as available matched clinical trials.

Results

The majority of patients had metastatic solid tumors (73.7%), mostly progressive (77.3%) after a mean of 2.0 lines of standard treatment. Diagnostic recommendations resulted in 867 molecular diagnostic tests for 172 patients (five per case), including exome analysis in 36 cases (18.2%). With a median turnaround time of 28 days, treatment recommendations were given to 104 patients (52.5%). These included single-agent targeted therapies (42.3%), checkpoint inhibitors (37.5%), and combination therapies (18.3%). Treatment recommendations were implemented in 33 of 104 patients (31.7%), of whom 19 (57.6%) showed stable disease or partial response, including 14 patients (7.1% of the entire population) receiving off-label treatments.

Conclusion

Personalized extended molecular-guided patient care is effective for a small but clinically meaningful proportion of patients in challenging clinical situations. Limited access to targeted drugs, lack of trials, and submission at late disease stage prevents broader applicability, whereas genome-wide analyses are not a strict requirement for predictive molecular testing.
FOS, a Critical Downstream Mediator of PGR and EGF Signaling Necessary for Ovulatory Prostaglandins in the Human Ovary
Authors: Choi Yohan , Rosewell Katherine L , Brännström Mats , Akin James W , Curry Thomas E , Jo Misung
Published: August 2018

Context

Fos null mice failed to ovulate and form a corpus luteum (CL) even when given exogenous gonadotropins, suggesting that ovarian Fos expression is critical for successful ovulation and CL formation. However, little is known about FOS in the human ovary.

Objectives

To determine the expression, regulation, and function of FOS in human periovulatory follicles.

Design/Participants

Timed periovulatory follicles were obtained from normally cycling women. Granulosa/lutein cells were collected from in vitro fertilization patients.

Main Outcome Measures

The in vivo expression after human chorionic gonadotropin (hCG) administration and in vitro regulation of FOS, JUN, JUNB, and JUND was evaluated at the mRNA and protein level. Binding of progesterone receptor (PGR) and FOS to their target genes was assessed by chromatin immunoprecipitation analyses. Prostaglandin E2 (PGE2) and progesterone were measured.

Results

The expression of FOS, JUNB, and JUND drastically increased in ovulatory follicles after hCG administration. In human granulosa/lutein cell cultures, hCG increased the expression of FOS and JUN proteins. Inhibitors of PGR and epidermal growth factor (EGF) receptors reduced hCG-induced increases in the expression and phosphorylation of FOS. PGR bound to the FOS gene. A selective FOS inhibitor blocked hCG-induced increases in PGE2 and the expression of prostaglandin (PG) synthases and transporters (PTGES, SLCO2A1, and ABCC1). FOS bound to the promoter regions of these genes.

Conclusions

The increase of FOS/activator protein 1 in human periovulatory follicles after hCG administration is mediated by collaborative actions of PGR and EGF signaling and critical for the upregulated expression of key ovulatory genes required for the rise in ovulatory PG in human granulosa cells.
Comparison of Intermittent Intravenous Boluses of Phenylephrine and Norepinephrine to Prevent and Treat Spinal-Induced Hypotension in Cesarean Deliveries: Randomized Controlled Trial
Authors: Sharkey Aidan M. , Siddiqui Naveed , Downey Kristi , Ye Xiang Y. , Guevara Jennifer , Carvalho Jose C. A.
Published: August 2018

BACKGROUND:

Phenylephrine (PE) is currently the vasopressor of choice to prevent and treat spinal-induced hypotension at cesarean delivery (CD). However, its use is often associated with reflex bradycardia. Norepinephrine (NE) has been put forward as an alternative vasopressor during CD due to its ability to treat hypotension while maintaining heart rate (HR). Recent studies have focused on the role of NE used as an infusion with favorable results compared to PE. No studies have compared equipotent bolus doses of PE and NE at CD. We hypothesized that when used in equipotent doses as an intermittent bolus regimen to prevent and treat spinal-induced hypotension, NE would result in a reduction in the incidence of bradycardia compared to PE.

METHODS:

This was a double-blind, randomized clinical trial of women undergoing elective CD under spinal anesthesia. Women were randomized to receive either PE 100 µg or NE 6 µg when the systolic blood pressure (SBP) was below baseline. In addition to the randomized treatment, ephedrine was given intravenously to both groups if the SBP was below baseline and the HR <60 bpm or if the SBP was <80% of baseline for 2 consecutive readings. The primary outcome was bradycardia (HR <50 bpm) in the predelivery period. Secondary outcomes included hypotension (SBP <80% of baseline), hypertension (SBP >120% of baseline), tachycardia (HR >120% of baseline), ≥2 episodes of bradycardia, nausea, vomiting, umbilical artery and vein blood gases, and Apgar scores.

RESULTS:

One hundred twelve patients were randomized. The incidence of bradycardia was lower in the NE group compared to the PE group (10.7% vs 37.5%; P < .001; difference [95% confidence interval {CI}], −26.8% [−41.8% to −11.7%]), implying an estimated 71% relative reduction (95% CI, 35%–88%). The distribution of the number of bradycardia episodes was also different between the 2 groups (P = .007). Further testing showed that the patients in the PE group had a higher risk of multiple bradycardia episodes (≥2 episodes) compared to the NE group (19.6% for PE versus 3.6% for NE; P = .008). The proportion of patients requiring rescue boluses of ephedrine was lower in the NE group compared to the PE group (7.2% for NE versus 21.4% for PE; P < .03; difference [95% CI], −14.3% [−27.0% to −1.6%]). No differences were observed between the 2 groups in the incidence of other secondary outcomes.

CONCLUSIONS:

When used as an intermittent bolus regimen to prevent and treat spinal-induced hypotension during CD, NE resulted in a significant reduction in the incidence of bradycardia as compared to an equipotent bolus regimen of PE. We conclude that the hemodynamic profile offered by NE during CD is superior to that of PE due to less fluctuations in HR and possibly cardiac output.
Comparative Regimens of Lipid Rescue From Bupivacaine-Induced Asystole in a Rat Model
Authors: Liu Le , Jin Zhousheng , Cai Xixi , Xia Yun , Zhang Meiling , Papadimos Thomas J. , Xu Xuzhong , Shi Kejian
Published: August 2018

BACKGROUND:

It is currently unknown whether bupivacaine-induced asystole is better resuscitated with lipid emulsion (LE) administered peripherally or centrally, and whether different LE regimens administered peripherally demonstrated similar effects. In this study, we compared the effects of various regimens of lipid administration in a rat model of bupivacaine-induced asystole.

METHODS:

Forty-five adult male Sprague-Dawley rats were subjected to bupivacaine-induced asystole and randomly divided into 3 lipid regimens groups: (1) 20% LE was administered continuously via the internal jugular vein (CV-infusion group); (2) 20% LE was administered continuously via the tail vein (PV-infusion group); and (3) 20% LE was administered as divided boluses via the tail vein (PV-bolus group). The maximum dose of LE did not exceed 10 mL·kg−1. External chest compressions were administered until the return of spontaneous circulation (ROSC) or the end of a 40-minute resuscitation period.

RESULTS:

The survival rate, rate of ROSC, systolic blood pressure, heart rate, heart rate–blood pressure product, and coronary perfusion pressure during 2–40 minutes in the CV-infusion and PV-bolus groups were significantly higher than those in the PV-infusion group (P < .01), and the plasma total bupivacaine concentration and myocardial bupivacaine content were significantly lower (P < .05). Time to heartbeat return and time to ROSC in the CV-infusion and PV-bolus groups were significantly shorter than those in the PV-infusion group (P < .05).

CONCLUSIONS:

In the rat model of bupivacaine-induced asystole, a divided LE bolus regimen administered peripherally provided a better resuscitation outcome than that of a continuous LE infusion regimen peripherally, and performed in a similar fashion as the continuous LE infusion regimen administered centrally.
Drosophila mef2is essential for normal mushroom body and wing development
Authors: Crittenden Jill R. , Skoulakis Efthimios M. C. , Goldstein Elliott. S. , Davis Ronald L.
Published: August 2018

MEF2 (myocyte enhancer factor 2) transcription factors are found in the brain and muscle of insects and vertebrates and are essential for the differentiation of multiple cell types. We show that in the fruitfly Drosophila, MEF2 is essential for the formation of mushroom bodies in the embryonic brain and for the normal development of wings in the adult. In embryos mutant for mef2, there is a striking reduction in the number of mushroom body neurons and their axon bundles are not detectable. The onset of MEF2 expression in neurons of the mushroom bodies coincides with their formation in the embryo and, in larvae, expression is restricted to post-mitotic neurons. In flies with a mef2 point mutation that disrupts nuclear localization, we find that MEF2 is restricted to a subset of Kenyon cells that project to the α/β, and γ axonal lobes of the mushroom bodies, but not to those forming the α‘/β’ lobes.
The small G protein Arl8 contributes to lysosomal function and long-range axonal transport in Drosophila
Authors: Rosa-Ferreira Cláudia , Sweeney Sean T. , Munro Sean
Published: August 2018

The small GTPase Arl8 has emerged as a major regulatory GTPase on lysosomes. Studies in mammalian cells have shown that it regulates both fusion with late endosomes and also lysosomal motility. In its active, GTP-bound, state it recruits to lysosomes the HOPS endosomal tethering complex and also proteins that link lysosomes to microtubule motors such as the kinesin adaptor PLEKHM2. To gain further insights into Arl8 biology we examined the single Drosophila ortholog. Drosophila Arl8 is essential for viability, and mitotic clones of mutant cells are able to continue to divide but show perturbation of the late endocytic pathway. Progeny lacking Arl8 die as late larvae with movement paralysis characteristic of defects in neuronal function. This phenotype was rescued by expression of Arl8 in motor neurons. Examination of these neurons in the mutant larvae revealed smaller synapses and axons with elevated levels of carriers containing synaptic components. Affinity chromatography revealed binding of Drosophila Arl8 to the HOPS complex, and to the Drosophila ortholog of RILP, a protein that in mammals recruits dynein to late endosomes, with dynein being known to be required for neuronal transport. Thus Drosophila Arl8 controls late endocytic function and transport via at least two distinct effectors.