bluuebunny/crossref_metadata_2025 huggingface dataset:
A longitudinal investigation of the role of parental responses in predicting children's post‐traumatic distress
Authors: Hiller Rachel M. , Meiser‐Stedman Richard , Lobo Sarah , Creswell Cathy , Fearon Pasco , Ehlers Anke , Murray Lynne , Halligan Sarah L.
Published: December 2017

Background

While parental post‐trauma support is considered theoretically important for child adjustment, empirical evidence concerning the specific aspects of parental responding that influence child post‐traumatic distress, or the processes via which any such impacts occur, is extremely limited. We conducted a longitudinal examination of whether parental post‐trauma appraisals, trauma‐specific support style and general parenting style predicted child post‐traumatic stress symptom severity (PTSS) following trauma; and whether such influences operated via the child's own appraisals and coping style.

Method

We recruited 132 parent–child pairs following children's experience of acute trauma. We examined whether parental responses assessed at 1‐month post‐trauma, predicted child PTSS at 6‐month follow‐up. Parental trauma‐specific appraisals and responses, and general parenting style, were assessed via both self‐report and direct observations. Child‐report questionnaires were used to assess PTSS and potential mediators.

Results

Initial parent negative appraisals and encouragement of avoidant coping were associated with higher child‐reported PTSS at 6‐month follow‐up. Predictive effects were maintained even when controlling for initial child symptom levels. Observational assessments broadly supported conclusions from self‐report. There was evidence that parental influences may operate, in part, by influencing the child's own appraisals and coping responses. In contrast, there was no evidence for an influence of more “adaptive” support or general parenting style on child PTSS.

Conclusions

Findings provide important insight into how elements of social support may influence child post‐trauma outcomes.
The high societal costs of childhood conduct problems: evidence from administrative records up to age 38 in a longitudinal birth cohort
Authors: Rivenbark Joshua G. , Odgers Candice L. , Caspi Avshalom , Harrington HonaLee , Hogan Sean , Houts Renate M. , Poulton Richie , Moffitt Terrie E.
Published: December 2017

Background

Children with conduct problems that persist into adulthood are at increased risk for future behavioral, health, and social problems. However, the longer term public service usage among these children has not been fully documented. To aid public health and intervention planning, adult service usage across criminal justice, health care, and social welfare domains is compared among all individuals from a representative cohort who followed different conduct problem trajectories from childhood into adulthood.

Methods

Participants are from the Dunedin Multidisciplinary Health and Development Study, a prospective, representative cohort of consecutive births (N = 1,037) from April 1972 to March 1973 in Dunedin, New Zealand. Regression analyses were used to compare levels of public service usage up to age 38, gathered via administrative and electronic medical records, between participants who displayed distinct subtypes of childhood conduct problems (low, childhood‐limited, adolescent‐onset, and life‐course persistent).

Results

Children exhibiting life‐course persistent conduct problems used significantly more services as adults than those with low levels of childhood conduct problems. Although this group comprised only 9.0% of the population, they accounted for 53.3% of all convictions, 15.7% of emergency department visits, 20.5% of prescription fills, 13.1% of injury claims, and 24.7% of welfare benefit months. Half of this group (50.0%) also accrued high service use across all three domains of criminal justice, health, and social welfare services, as compared to only 11.3% of those with low conduct problems (OR = 7.27, 95% CI = 4.42–12.0).

Conclusions

Conduct problems in childhood signal high future costs in terms of service utilization across multiple sectors. Future evaluations of interventions aimed at conduct problems should also track potential reductions in health burden and service usage that stretch into midlife.
Cost‐effectiveness of cognitive therapy as an early intervention for post‐traumatic stress disorder in children and adolescents: a trial based evaluation and model
Authors: Shearer James , Papanikolaou Nestor , Meiser‐Stedman Richard , McKinnon Anna , Dalgleish Tim , Smith Patrick , Dixon Clare , Byford Sarah
Published: December 2017

Background

Untreated post‐traumatic stress disorder (PTSD) in children and adolescents is associated with a considerable economic burden on the health system, families and society. Recent research has demonstrated the potential efficacy of cognitive therapy as an early intervention for PTSD in children and adolescents. Children who experienced a single traumatic event in the previous two to six months and were randomized to cognitive therapy for PTSD (CT‐PTSD) were significantly more likely to be PTSD‐free compared to those randomized to usual care represented by waitlist control. The current study evaluated the economic impact of improvements in the treatment of PTSD in children and adolescents.

Methods

A cost‐effectiveness analysis was conducted from the national health service/personal social services perspective with outcomes expressed as quality‐adjusted life years (QALYs). Patient level costs and outcomes were collected during the 11 week clinical trial and extrapolated to a three year time horizon using economic modelling methods. Uncertainty was estimated using probabilistic sensitivity analysis and assumptions were tested using one way sensitivity analysis.

Results

The incremental cost‐effectiveness ratio at 3 years was £2,205 per QALY with a 60%–69% probability of CT‐PTSD being cost‐effective compared to usual care at the UK £20,000 to £30,000 per QALY decision threshold.

Conclusions

This study provides preliminary evidence for the cost‐effectiveness of cognitive therapy in this treatment population. Larger pragmatic trials with longer follow‐up are indicated.
Prospective test of the developmental propensity model of antisocial behavior: from childhood and adolescence into early adulthood
Authors: Lahey Benjamin B. , Class Quetzal A. , Zald David H. , Rathouz Paul J. , Applegate Brooks , Waldman Irwin D.
Published: December 2017

Background

The developmental propensity model of antisocial behavior posits that several dispositional characteristics of children transact with the environment to influence the likelihood of learning antisocial behavior across development. Specifically, greater dispositional negative emotionality, greater daring, and lower prosociality—operationally, the inverse of callousness— and lower cognitive abilities are each predicted to increase risk for developing antisocial behavior.

Methods

Prospective tests of key predictions derived from the model were conducted in a high‐risk sample of 499 twins who were assessed on dispositions at 10–17 years of age and assessed for antisocial personality disorder (APD) symptoms at 22–31 years of age. Predictions were tested separately for parent and youth informants on the dispositions using multiple regressions that adjusted for oversampling, nonresponse, and clustering within twin pairs, controlling demographic factors and time since the first assessment.

Results

Consistent with predictions, greater numbers of APD symptoms in adulthood were independently predicted over a 10–15 year span by higher youth ratings on negative emotionality and daring and lower youth ratings on prosociality, and by parent ratings of greater negative emotionality and lower prosociality. A measure of working memory did not predict APD symptoms.

Conclusions

These findings support future research on the role of these dispositions in the development of antisocial behavior.
Potassium phosphites in the protection of common bean plants against anthracnose and biochemical defence responses
Authors: Costa Bruno Henrique Garcia , de Resende Mário Lúcio Vilela , Monteiro Ana Cristina Andrade , Ribeiro Júnior Pedro Martins , Botelho Deila Magna dos Santos , Silva Bruno Marques da
Published: December 2017

The aim of this study was to investigate the effectiveness of potassium phosphites for the control of anthracnose and the mode of action of these products on common bean plants against Colletotrichum lindemuthianum, comparing it with the standard resistance inducer acibenzolar‐S‐methyl. The protection of plants against anthracnose was evaluated in greenhouse after treatment with potassium phosphites (Phosphite A and B, 5.0 ml/L), acibenzolar‐S‐methyl (0.25 g/L), or no treatment (control). Two sprayings of the treatments were performed, respectively, at V4 stage (three trifoliate leaves) and at the R5 stage (flower buds present). The inoculation with C. lindemuthianum was performed 5 days after the first spraying. Phosphite formulations A and B reduced the severity of anthracnose by 68.7% and 55.6%, respectively, and the presence of phosphites in the leaf tissues were detected at concentrations between 1 and 3 mm by 7 days after spraying. These same concentrations of phosphites reduced the mycelial growth of C. lindemuthianum in vitro by 15.0% to 25.7%. In addition, the activities of defence enzymes and the levels of phenolic compounds and lignin were assessed. Phosphite treatments enhanced the activity of various enzymes, including superoxide dismutase, peroxidase, chitinase, and β‐1,3‐glucanase, and increased the lignin and a small increase in the levels of soluble phenolics. This study provides evidence that phosphite treatments control anthracnose by acting directly on C. lindemuthianum and by inducing the production of defence responses.
Phylogeny, morphology and pathogenicity of Elsinoë ampelina, the causal agent of grapevine anthracnose in Brazil and Australia
Authors: Santos Ricardo Feliciano dos , Spósito Marcel Bellato , Ayres Matthew Ronald , Sosnowski Mark Roman
Published: December 2017

Anthracnose caused by Elsinoë ampelina is one of the most important table grape diseases in humid regions in Brazil and Australia. The objective of this study was to characterize E. ampelina isolates from Brazil and Australia by means of phylogenetic analyses, morphological features and pathogenicity tests. Phylogenetic relationships among 35 isolates were determined based on a data set of internal transcribed spacer (ITS), histone H3 (HIS3) and elongation factor 1‐α (TEF) sequences. In phylogenetic tree analyses, using a combined ITS and TEF sequence alignment, all E. ampelina isolates were clustered together in a single well‐supported clade. In contrast to the absence of genetic variability within ITS and TEF sequences, HIS3 sequences showed 54 polymorphic sites. The haplotype network generated from HIS3 data set showed four distinct haplotypes. EA1 was the predominant haplotype including 29 isolates from both countries. High genetic variability was observed in two Brazilian isolates, haplotype EA4, which may have lost the intron region during species evolution. Colony colours differed between Brazilian and Australian isolates, but showed similar wrinkled colony texture, absence of spores, sparse‐to‐absent white aerial mycelium and slow growth (0.049–0.060 mm/day). Brazilian isolates produced conidia of 5.65 × 2.65 μm, larger than conidia from Australian isolates, which measured 5.14 × 2.30 μm. In pathogenicity tests, all nine Australian isolates inoculated were pathogenic on detached canes and potted vines of table grape.
Plasma NT‐proBNP and Cell‐Free DNA Concentrations after Prolonged Strenuous Exercise in Working Farm Dogs
Authors: Hunt H. , Cave N. , Bridges J. , Gedye K. , Hill K.
Published: December 2017

Background

Plasma N‐terminal pro–B‐type natriuretic peptide (NT‐proBNP) concentration is increased in dogs with myocardial dysfunction, and cell‐free DNA (cfDNA) increases in numerous disease states. In humans, both of these biomarkers can be altered after endurance exercise.

Objective

To investigate the effect of prolonged strenuous exercise on circulating NT‐proBNP and cfDNA concentrations in working farm dogs.

Animals

Six healthy, privately owned working farm dogs (4 Huntaways and 2 heading dogs) from the same hill country farm in New Zealand.

Methods

Prospective, nonrandomised cohort study. Venous blood samples were collected before and after the dogs worked over 4 days. Plasma NT‐proBNP concentrations were measured by a commercially available ELISA assay and cfDNA concentrations were determined by fluorometry without prior DNA extraction.

Results

The baseline (before work, Day 1) median plasma NT‐proBNP concentration was 664 pmol/L. A linear mixed‐effects model showed that work increased plasma NT‐proBNP concentrations by 101 ± 9% (P < 0.001), but with each consecutive day of work, NT‐proBNP concentrations declined by 16 ± 4% (P < 0.001). The baseline median plasma cfDNA concentration was 653 ng/mL, and plasma cfDNA concentrations increased by 138 ± 45 ng/mL after work (P = 0.004).

Conclusions and Clinical Importance

The plasma concentration of NT‐proBNP in healthy Huntaways and heading dogs after work can exceed the upper limit of the reference range. Results in dogs sampled on the day of prolonged strenuous exercise should be interpreted with caution. Plasma concentrations of cfDNA also increase with exercise, but further studies are needed to establish reference ranges in healthy dogs.
Pyelonephritis in Dogs: Retrospective Study of 47 Histologically Diagnosed Cases (2005–2015)
Authors: Bouillon J. , Snead E. , Caswell J. , Feng C. , Hélie P. , Lemetayer J.
Published: December 2017

Background

The clinicopathologic aspects of pyelonephritis have not been reported in companion animals.

Hypothesis/Objectives

To evaluate the prevalence of pyelonephritis diagnosed in dogs in a academic referral population, describe the clinical signs and the diagnostic test results in dogs with pyelonephritis, and identify concurrent disorders in order to determine potential risk factors for pyelonephritis.

Animals

Forty‐seven dogs with a histopathologic diagnosis of pyelonephritis from the teaching hospitals of three Canadian veterinary colleges.

Methods

Retrospective case series. Review of medical records and renal histologic sections.

Results

Pyelonephritis was diagnosed in 0.4–1.3% of the cases at necropsy. Clinical signs included anorexia or inappetence (n = 27, 57%), lethargy (n = 24, 51%), vomiting (n = 17, 36%), and dehydration (n = 12, 25%). Thirty‐five dogs (75%) had concomitant disease(s).Escherichia coliwas the most common pathogen isolated (37%). Pyelonephritis was classified as acute (n = 12, 26%), subacute (n = 9, 19%), and chronic (n = 26, 55%) disease; and mild (n = 7, 15%), moderate (n = 11, 24%), and severe (n = 28, 61%). Fever was significantly associated with histopathologically subacute pyelonephritis (P= 0.01).

Conclusions

In referral hospitals, pyelonephritis has a very low prevalence at necropsy. Nonspecific clinical presentation, concomitant diseases, and high variability in the diagnostic tests results make the antemortem diagnosis of pyelonephritis challenging. Neither the histopathologic stage nor the severity of the pyelonephritis was associated with fever, lumbar pain, or signs of a urinary tract infection (ie, lower urinary tract infection, upper urinary tract infection, or both) except for subacute pyelonephritis which was associated with fever.
BartonellaSeroepidemiology in Dogs from North America, 2008–2014
Authors: Lashnits E. , Correa M. , Hegarty B.C. , Birkenheuer A. , Breitschwerdt E.B.
Published: December 2017

Background

Improved understanding ofBartonellaspecies seroepidemiology in dogs may aid clinical decision making and enhance current understanding of naturally occurring arthropod vector transmission of this pathogen.

Objectives

To identify demographic groups in whichBartonellaexposure may be more likely, describe spatiotemporal variations inBartonellaseroreactivity, and examine co‐exposures to other canine vector‐borne diseases (CVBD).

Animals

A total of 15,451 serology specimens from dogs in North America were submitted to the North Carolina State University, College of Veterinary Medicine Vector Borne Disease Diagnostic Laboratory between January 1, 2008, and December 31, 2014.

Methods

Bartonella henselae,Bartonella koehlerae,andBartonella vinsoniisubspeciesberkhoffiiindirect fluorescent antibody (IFA) serology results, as well as results from a commercial assay kit screening forDirofilaria immitisantigen andEhrlichiaspecies,Anaplasma phagocytophilum, andBorrelia burgdorferiantibodies, andEhrlichia canis,Babesia canis,Babesia gibsoni, andRickettsiaspeciesIFAresults were reviewed retrospectively.

Results

Overall, 3.26% of dogs wereBartonellaspp. seroreactive;B. henselae(2.13%) andB. koehlerae(2.39%) were detected more frequently thanB. vinsoniisubsp.berkhoffii(1.42%,P < 0.0001). Intact males had higher seroreactivity (5.04%) than neutered males (2.87%,P < 0.0001) or intact or spayed females (3.22%,P = 0.0003). Mixed breed dogs had higher seroreactivity (4.45%) than purebred dogs (3.02%,P = 0.0002). There was no trend in seasonal seroreactivity; geographic patterns supported broad distribution of exposure, and co‐exposure with otherCVBDwas common.

Conclusions and Clinical Importance

Bartonellaspp. exposure was documented throughout North America and at any time of year. Male intact dogs, mixed breed dogs, and dogs exposed to otherCVBDhave higher seroreactivity to multipleBartonellaspecies.
The effect of interferon‐free regimens on health‐related quality of life in East Asian patients with chronic hepatitis C
Authors: Younossi Zobair M. , Stepanova Maria , Henry Linda , Han Kwang‐Hyub , Ahn Sang Hoon , Lim Young‐Suk , Chuang Wan‐Long , Kao Jia‐Horng , Kinh Nguyen , Lai Ching Lung , Yuen Man‐Fung , Chan Henry Lik‐Yuen , Lai Wei
Published: December 2017

Background

Interferon (IFN)‐based regimens cause significant impairment of health‐related quality of life (HRQL). Hepatitis C virus (HCV) cure with IFN‐free regimens improves HRQL. The effect of these regimens on HRQL in East Asian HCV patients is unclear due to lack of published evidence.

Aim

To assess HRQL in East Asian HCV patients treated with an IFN‐free regimen with sofosbuvir+ribavirin.

Methods

Patients completed Short Form‐36 (SF‐36) before, during and after treatment.

Results

686 subjects were included (China: 56.7%; S. Korea: 18.8%; Taiwan: 12.7%; genotype 2: 40.8%; genotype 1: 29.6%; genotype 3: 18.4%; genotype 6: 11.2%; cirrhosis: 13.4%; treatment‐naïve: 66.5%). Patients received either pegylated‐IFN, sofosbuvir, and ribavirin (IFN+SOF+RBV) for 12 weeks (n = 155, genotypes 1 and 6) or SOF+RBV for 12‐24 weeks (n = 531, all genotypes). The SVR‐12 rates were 95.5% and 96.0%; respectively (P = .76). Baseline HRQL scores were similar between treatment groups (all P > .05). By the end of treatment, the IFN‐treated group experienced significant declines in most HRQL scores (on average, by up to −13.3 points on a 0‐100 scale from the baseline level, P < .02) while subjects on SOF/RBV had milder impairments (up to −5.4 points). Achieving SVR‐12 was associated with HRQL improvement regardless of regimen (up to +2.9 points, P < .05). The use of IFN‐free treatment was a consistent independent predictor of higher HRQL scores during treatment (β: +2.1 to +10.7 points, P < .02).

Conclusions

East Asian HCV patients treated with an IFN‐free regimen had better on‐treatment HRQL scores. These data should inform policymakers about the comprehensive benefits of IFN‐free regimens in East Asian patients with HCV.
Long‐term follow‐up of ribavirin‐free DAA‐based treatment in HCV recurrence after orthotopic liver transplantation
Authors: Beinhardt Sandra , Al‐Zoairy Ramona , Kozbial Karin , Stättermayer Albert F. , Maieron Andreas , Stauber Rudolf , Strasser Michael , Zoller Heinz , Graziadei Ivo , Rasoul‐Rockenschaub Susanne , Trauner Michael , Ferenci Peter , Hofer Harald
Published: December 2017

Background & Aims

Excellent efficacy and safety profile of second‐generation DAA combinations improved treatment of chronic hepatitis C (HCV) as well as in HCV recurrence after orthotopic liver transplantation (OLT). The need of ribavirin addition is under debate as anaemia and decreased renal function are prevalent in transplant cohorts. The aim of this study was thus to assess safety and long‐term efficacy of RBV‐free DAA combinations in HCV‐recurrent patients after OLT.

Patients & Methods

A total of 62 OLT recipients (male: 50%/81%; age: 60.7 ± 8.5 years [mean ± SD]; GT ‐ 1: 48, GT ‐ 3: 9, GT ‐ 4: 5; cirrhosis: 34%/55% [7%/21% decompensated], fibrosing cholestatic hepatitis: 1%/2%) received RBV‐free treatment with second‐generation DAA combinations: sofosbuvir (SOF)/daclatasvir (DCV): 42%/68%, SOF/simeprevir (SMV): 10%/16%, SOF/ledipasvir (LDV): 6%/10% and PrOD: 4%/7%.

Results

Data of at least 96 weeks of FUP after treatment cessation (mean: 120; up to 167 weeks) were analysed. All patients showed on‐treatment response. By intention‐to‐treat (ITT) analysis, SVR12 was 97% (60/62, GT‐1a: 11/11 [100%]; 1b: 33/34 [97%]; 1g: 1/1 [100%]; subtype not specified: 2/2 [100%]; GT3a: 9/9 [100%]; GT4: 4/5 [80%]) compared to SVR96 of 89% (55/62). No late relapses occurred. In total, 16 severe adverse events occurred, including two newly diagnosed carcinoma (lung cancer, hepatocellular carcinoma). Six patients died; one at treatment week 24 (HCV‐RNA undetectable) and five during treatment‐free FUP and after achieving SVR (SVR4: N = 1, SVR12: N = 3, after SVR96: N = 1 respectively). Reasons for death were: multi‐organ failure (N = 4), impaired graft function (N = 1) and unknown (N = 1).

Conclusion

RBV‐free DAA combinations for the treatment of HCV recurrence after OLT are highly efficacious and well tolerated. Our long‐term data show that viral eradication is durable but not necessarily translated into beneficial long‐term clinical outcome.
Overview of carbon and nitrogen catabolite metabolism in the virulence of human pathogenic fungi
Authors: Ries Laure Nicolas Annick , Beattie Sarah , Cramer Robert A. , Goldman Gustavo H.
Published: December 2017

It is estimated that fungal infections, caused most commonly by Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, result in more deaths annually than malaria or tuberculosis. It has long been hypothesized the fungal metabolism plays a critical role in virulence though specific nutrient sources utilized by human pathogenic fungi in vivo has remained enigmatic. However, the metabolic utilisation of preferred carbon and nitrogen sources, encountered in a host niche‐dependent manner, is known as carbon catabolite and nitrogen catabolite repression (CCR, NCR), and has been shown to be important for virulence. Several sensory and uptake systems exist, including carbon and nitrogen source‐specific sensors and transporters, that allow scavenging of preferred nutrient sources. Subsequent metabolic utilisation is governed by transcription factors, whose functions and essentiality differ between fungal species. Furthermore, additional factors exist that contribute to the implementation of CCR and NCR. The role of the CCR and NCR‐related factors in virulence varies greatly between fungal species and a substantial gap in knowledge exists regarding specific pathways. Further elucidation of carbon and nitrogen metabolism mechanisms is therefore required in a fungal species‐ and animal model‐specific manner in order to screen for targets that are potential candidates for anti‐fungal drug development.
Fundamental movement skills in adolescents: Secular trends from 2003 to 2010 and associations with physical activity and BMI
Authors: Huotari P. , Heikinaro‐Johansson P. , Watt A. , Jaakkola T.
Published: December 2017

The aim of this study was to examine the secular trends in fundamental movement skills (FMS) among 15‐ to 16‐year‐old adolescents at 2 assessment points scheduled in 2003 and 2010 and to investigate the associations between FMS, physical activity (PA), and body mass index (BMI). In 2003, self‐reported PA, weight and height, and objective FMS scores were collected from 2390 students, and in 2010, similar data were generated from a second sample of 1346 students. FMS were assessed during both assessment phases using 3 identical objective FMS tests that were figure 8 dribbling, jumping laterally, and coordination track tests. This study indicated that the sum index of FMS did not change among the boys and the girls between 2 data collection points. However, findings demonstrated a secular decline in coordination test scores in both gender groups between 2 measurement points but an improvement in girls’ object control skills between 2003 and 2010. The results also showed that FMS had a significant main effect on BMI in both gender groups, whereas the main effect of PA on BMI was not significant for either gender group. Results also demonstrated that there was no significant interaction effect between FMS and PA on BMI in either of the girls’ or the boys’ groups.
Structural insight into the methyltransfer mechanism of the bifunctional Trm5
Authors: Wang Caiyan , Jia Qian , Zeng Jianhua , Chen Ran , Xie Wei
Published: December 2017

The precise placement of the PTPK motif leads to relaxed substrate specificity and double methylation capability of PaTrm5a.
Skiving stacked sheets of paper into test paper for rapid and multiplexed assay
Authors: Yang Mingzhu , Zhang Wei , Yang Junchuan , Hu Binfeng , Cao Fengjing , Zheng Wenshu , Chen Yiping , Jiang Xingyu
Published: December 2017

Stacked paper skiving paves the way for industrial manufacturing of paper-based analytical devices for barcode assays.
3D printing of bacteria into functional complex materials
Authors: Schaffner Manuel , Rühs Patrick A. , Coulter Fergal , Kilcher Samuel , Studart André R.
Published: December 2017

3D printing of bacteria-laden hydrogels enables the digital fabrication of complex functional materials.
Sustained T follicular helper cell response is essential for control of chronic viral infection
Authors: Greczmiel Ute , Kräutler Nike Julia , Pedrioli Alessandro , Bartsch Ilka , Agnellini Paola , Bedenikovic Gregor , Harker James , Richter Kirsten , Oxenius Annette
Published: December 2017

CXCR5
+
T follicular helper cells promote generation of neutralizing antibodies in response to chronic viral infection.
Migratory CD11b
+
conventional dendritic cells induce T follicular helper cell–dependent antibody responses
Authors: Krishnaswamy Jayendra Kumar , Gowthaman Uthaman , Zhang Biyan , Mattsson Johan , Szeponik Louis , Liu Dong , Wu Renee , White Theresa , Calabro Samuele , Xu Lan , Collet Magalie A. , Yurieva Marina , Alsén Samuel , Fogelstrand Per , Walter Anne , Heath William R. , Mueller Scott N. , Yrlid Ulf , Williams Adam , Eisenbarth Stephanie C.
Published: December 2017

Conventional DC2s are necessary and sufficient for priming T follicular helper cells.
Late arising T follicular helper cells cultivate the B cell crop during chronic infections
Authors: Kahan Shannon M. , Zajac Allan J.
Published: December 2017

Follicular helper CD4
+
T cells are essential for the development of neutralizing antibodies that contain chronic viral infection. See the related research article by

Greczmiel
et al.
Systemic lupus erythematosus (SLE): an unusual cause of ileocolic intussusception
Authors: Glijn Naomi , Korswagen Lindy-Anne , Lam-Tse Wai-Kwan
Published: December 2017

Intussusception is a rare diagnosis in adults. Gastrointestinal involvement is not unusual in systemic lupus erythematosus (SLE).1A case of intussusception as first presenting symptom of SLE is described. A 50-year-old woman of Chinese origin came to the emergency room with symptoms of high fever, nausea, vomiting and weight loss of 10 kg. Three months before, an episode with abdominal pain due to ileal invagination in the colon occurred. Laboratory analysis showed: thrombocytopaenia, lymphopaenia, positive antinuclear antibody, antidouble-stranded DNA, Coombs tests and low C3 in combination with an active urine sediment and proteinuria. CT and positron emission tomography scan showed lymphadenopathy, but no other abnormalities. Axillar lymph node biopsy showed no abnormalities. The diagnosis new-onset SLE was made. Prednisone treatment was started and soon thereafter tapered, azathioprine and hydroxychloroquine were added. During follow-up, the SLE remained in remission. SLE is a rare cause of ileocolic intussusception and ileocolic intussusception may be the first presenting symptom.
Leg length discrepancy: the importance of a complete history and examination
Authors: Coffey Duncan , Hudson-Phillips Sarah Patricia , Radha Sarkhell Saadi , Ball Simon
Published: December 2017

A 26-year-old woman with a 1-year history of right knee pain had failed to respond to analgesia and activity modification in the community. Her general practitioner referred her to the orthopaedic department for specialist review. A thorough history revealed that she had multiple orthopaedic interventions as a child. The patient had significant postoperative infection of the left knee following knee surgery at 7 years of age. Examination demonstrated the presence of a limp, scoliosis and suspected leg length discrepancy. Plain film radiography confirmed the presence of leg length discrepancy, with the right limb measuring 30 mm longer than the left. The leg length discrepancy was likely secondary to a growth arrest of the left knee following the postoperative infection in childhood. The patient was managed with physiotherapy and heel raises and received regular orthopaedic follow-up.
Estimating the effects of second-line therapy for type 2 diabetes mellitus: retrospective cohort study
Authors: Gottlieb Assaf , Yanover Chen , Cahan Amos , Goldschmidt Yaara
Published: December 2017

Objective

Metformin is the recommended initial drug treatment in type 2 diabetes mellitus, but there is no clearly preferred choice for an additional drug when indicated. We compare the counterfactual drug effectiveness in lowering glycated hemoglobin (HbA1c) levels and effect on body mass index (BMI) of four diabetes second-line drug classes using electronic health records.

Study design and setting

Retrospective analysis of electronic health records of US-based patients in the Explorys database using causal inference methodology to adjust for patient censoring and confounders.

Participants and exposures

Our cohort consisted of more than 40 000 patients with type 2 diabetes, prescribed metformin along with a drug out of four second-line drug classes—sulfonylureas, thiazolidinediones, dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide-1 agonists—during the years 2000–2015. Roughly, 17 000 of these patients were followed for 12 months after being prescribed a second-line drug.

Main outcome measures

HbA1c and BMI of these patients after 6 and 12 months following treatment.

Results

We demonstrate that all four drug classes reduce HbA1c levels, but the effect of sulfonylureas after 6 and 12 months of treatment is less pronounced compared with other classes. We also estimate that DPP-4 inhibitors decrease body weight significantly more than sulfonylureas and thiazolidinediones.

Conclusion

Our results are in line with current knowledge on second-line drug effectiveness and effect on BMI. They demonstrate that causal inference from electronic health records is an effective way for conducting multitreatment causal inference studies.
Comparison of haemoglobin assessments by HemoCue and two automated haematology analysers in young Laotian children
Authors: Hinnouho Guy-Marino , Barffour Maxwell A , Wessells K Ryan , Brown Kenneth H , Kounnavong Sengchanh , Chanhthavong Bigphone , Ratsavong Kethmany , Kewcharoenwong Chidchamai , Hess Sonja Y
Published: December 2017

Background

Haemoglobin (Hb) assessment by Hemocue is used widely for anaemia screening in both adults and children. However, few studies have compared the diagnostic accuracy of Hemocue with an automated haematology analyser in young children.

Aim

To compare Hb concentrations by Hemocue Hb301 and two automated haematology analysers in young children in rural communities of Lao PDR.

Methods

Capillary blood was collected from 6-month-old to 23-month-old children (n=1487) for determination of Hb concentration by Hemocue Hb301. On the same day, venous blood was collected for complete blood count using one of two haematology analysers (XT-1800i, Sysmex, and BC-3000Plus, Mindray Medical International). In a subsample of children (n=129), venous Hb was also measured by HemoCue Hb301. Agreement between the two methods was estimated using Bland-Altman plots.

Results

Mean capillary Hb by Hemocue was significantly higher than mean venous Hb by haematology analysers combined (108.4±10.3 g/L vs 102.3±13.1 g/L; P<0.001), resulting in a significantly lower anaemia prevalence (Hb <110 g/L) by Hemocue (53.7% vs 73.9%; P<0.001). The Bland-Altman assessment of agreement showed a bias of 6.1 g/L and limits of agreement were −11.5 g/L to 23.7 g/L. Mean venous Hb concentration by Hemocue Hb301 (113.6±14.0 g/L) was significantly higher than mean capillary Hb concentration by Hemocue Hb301 (110.0±10.7; P=0.03 g/L), which in turn was significantly higher than mean venous Hb concentration by the Mindray BC-3000Plus (102.3±17.4 g/L).

Conclusion

Capillary and venous Hb concentrations assessed by Hemocue Hb301 showed poor agreement compared with venous Hb by automated haematology analysers, resulting in significantly different anaemia prevalences.
Detection of genome-wide copy number variants in myeloid malignancies using next-generation sequencing
Authors: Shen Wei , Paxton Christian N , Szankasi Philippe , Longhurst Maria , Schumacher Jonathan A , Frizzell Kimberly A , Sorrells Shelly M , Clayton Adam L , Jattani Rakhi P , Patel Jay L , Toydemir Reha , Kelley Todd W , Xu Xinjie
Published: December 2017

Aims

Genetic abnormalities, including copy number variants (CNV), copy number neutral loss of heterozygosity (CN-LOH) and gene mutations, underlie the pathogenesis of myeloid malignancies and serve as important diagnostic, prognostic and/or therapeutic markers. Currently, multiple testing strategies are required for comprehensive genetic testing in myeloid malignancies. The aim of this proof-of-principle study was to investigate the feasibility of combining detection of genome-wide large CNVs, CN-LOH and targeted gene mutations into a single assay using next-generation sequencing (NGS).

Methods

For genome-wide CNV detection, we designed a single nucleotide polymorphism (SNP) sequencing backbone with 22 762 SNP regions evenly distributed across the entire genome. For targeted mutation detection, 62 frequently mutated genes in myeloid malignancies were targeted. We combined this SNP sequencing backbone with a targeted mutation panel, and sequenced 9 healthy individuals and 16 patients with myeloid malignancies using NGS.

Results

We detected 52 somatic CNVs, 11 instances of CN-LOH and 39 oncogenic mutations in the 16 patients with myeloid malignancies, and none in the 9 healthy individuals. All CNVs and CN-LOH were confirmed by SNP microarray analysis.

Conclusions

We describe a genome-wide SNP sequencing backbone which allows for sensitive detection of genome-wide CNVs and CN-LOH using NGS. This proof-of-principle study has demonstrated that this strategy can provide more comprehensive genetic profiling for patients with myeloid malignancies using a single assay.
Numerical and experimental study on influence of installation effects on behaviour of helical anchors in very dense sand
Authors: Pérez Zorany Agudelo , Schiavon José Antonio , Tsuha Cristina de Hollanda Cavalcanti , Dias Daniel , Thorel Luc
Published: December 2017

The use of helical anchors has been increasing in recent years; however, the current understanding of its behaviour does not allow for reliable estimates of uplift capacity and load–displacement response. The need for improvement of the design methods has motivated the present study, which investigates the effect of installation on the helical anchor response in very dense sand. This work is divided into three parts. The first part describes the results of centrifuge model tests and microtomographic analysis performed to examine the uplift response of a single-helix anchor and the soil disturbance caused by the installation process. The aim of these tests was to define appropriate hypotheses for the numerical prediction of helical anchor performance. In the second part, the load–displacement curve of a tested helical anchor was numerically simulated with the finite difference software FLAC3D, considering the installation effect observed experimentally. In the third part of the paper, the adjusted numerical model was used in a parametric analysis to provide some guidelines for the design of helical anchors in dense sand. Additionally, from the results of the numerical investigation and experimental observations, two different approaches are presented for improving the accuracy of analytical predictions of helical anchor capacity. Both suggested methods showed good agreement with centrifuge and field testing data.
Evidence for a grounded ice sheet in the central North Sea during the early Middle Pleistocene Donian Glaciation
Authors: Bendixen Carina , Lamb Rachel M. , Huuse Mads , Boldreel Lars O. , Jensen Jørn B. , Clausen Ole R.
Published: December 2017

Interpretation of 3D seismic data from the central North Sea yields evidence of a pre-MIS (Marine Isotope Stage) 12 grounded glaciation. The glaciotectonic complex shows buried push moraines resulting from the thrusting of multiple ice advance phases with horizontal shortening of 35 – 50%. The earliest feature observed within the complex, a hill–hole pair, represents the initial glaciation of the area. This is overlain and deformed by multiple thrust units with numerous inferred ice-flow directions. The thrust deformation observed shares characteristics with kinematic processes, push moraines and static gravity processes, seen as gravity spreading and contraction. The glaciotectonic complex in its entirety is interpreted to correlate to a pre-Elsterian glaciation, becaue of its stratigraphic position below central North Sea tunnel valleys, estimated to be Elsterian in age (MIS 12; 450 ka). The study proposes that the thrust complex correlates to the Donian glaciation in Russia (MIS 16; 600 ka) with ice sourced from Norway. The complex therefore represents a glaciation where a significant area of the central North Sea was covered by an ice sheet, 200 kyr prior to the Elsterian. This study highlights the fragmentary record of pre-Elsterian glaciations and the importance of incorporating offshore sedimentary archives and regional frameworks when reconstructing Pleistocene climate change.
Deconstruction of a Metastatic Tumor Microenvironment Reveals a Common Matrix Response in Human Cancers
Authors: Pearce Oliver M.T. , Delaine-Smith Robin M. , Maniati Eleni , Nichols Sam , Wang Jun , Böhm Steffen , Rajeeve Vinothini , Ullah Dayem , Chakravarty Probir , Jones Roanne R. , Montfort Anne , Dowe Tom , Gribben John , Jones J. Louise , Kocher Hemant M. , Serody Jonathan S. , Vincent Benjamin G. , Connelly John , Brenton James D. , Chelala Claude , Cutillas Pedro R. , Lockley Michelle , Bessant Conrad , Knight Martin M. , Balkwill Frances R.
Published: December 2017

We have profiled, for the first time, an evolving human metastatic microenvironment by measuring gene expression, matrisome proteomics, cytokine and chemokine levels, cellularity, extracellular matrix organization, and biomechanical properties, all on the same sample. Using biopsies of high-grade serous ovarian cancer metastases that ranged from minimal to extensive disease, we show how nonmalignant cell densities and cytokine networks evolve with disease progression. Multivariate integration of the different components allowed us to define, for the first time, gene and protein profiles that predict extent of disease and tissue stiffness, while also revealing the complexity and dynamic nature of matrisome remodeling during development of metastases. Although we studied a single metastatic site from one human malignancy, a pattern of expression of 22 matrisome genes distinguished patients with a shorter overall survival in ovarian and 12 other primary solid cancers, suggesting that there may be a common matrix response to human cancer.

Significance: Conducting multilevel analysis with data integration on biopsies with a range of disease involvement identifies important features of the evolving tumor microenvironment. The data suggest that despite the large spectrum of genomic alterations, some human malignancies may have a common and potentially targetable matrix response that influences the course of disease. Cancer Discov; 8(3); 304–19. ©2017 AACR.

This article is highlighted in the In This Issue feature, p. 253
The Independent Foreign Fiction Prize and Man Booker International Prize Merger
Authors: Bold Melanie Ramdarshan , Norrick-Rühl Corinna
Published: December 2017

There is a dramatic imbalance of cultural output in the global publishing industry. English-language publishers are disinclined to translate and publish foreign language books as a result of the popularity of English-language books and the high costs of translation. Three per cent is the oft-quoted number that indicates that foreign fiction in translation makes up only a minimal part of the UK book trade. This lack of bibliodiversity may have serious cultural consequences. There are thus several national and international initiatives to promote the publication and cultural capital of works in translation in order to reach a wider audience.

Book prizes are generally understood to have a positive impact on the discoverability of a title and consequent sales; winning authors, as well as those on the longlist and shortlist of prestigious prizes, can expect a significant boost in sales of the books in question. But in a culture where translated foreign fiction titles represent only a small percentage of books published, does this phenomenon extend to prizes for translated foreign fiction? This paper explores the—audience-building and sales-generating—impact of the UK’s most prestigious award for literature in translation, the Independent Foreign Fiction Prize (IFFP), in particular in light of the prize’s recent merger with the Man Booker International Prize (MBIP), and speculates whether this may help with the ‘three per cent problem’.
Bibliotherapy
Authors: Canty Nick
Published: December 2017

This article discusses the historical development of bibliotherapy and how books can be used in the treatment of a range of minor mental health conditions. The article provides a brief historical account of how books have been used in institutions through the centuries and how the bibliotherapuetic process works through the use of texts from which the reader gains an insight into their personal situation by identifying with a character experiencing similar problems. Bibliotherapy as both clinical and community-based treatment is discussed through a number of case studies from the critical literature, in particular the Ayrshire Read Yourself Well scheme and the Reading Well/Books on Prescription scheme. The results of a medical trial on the benefits of reading a novel based on MRI (magnetic resonance imaging) scans of readers are then discussed.
Law, Religion, and the Rule of Law from a Normative-Positivistic Perspective
Authors: Englard Izhak
Published: December 2017

The paper starts with an analysis, based on Hans Kelsen’s methodology, about the difference between law and morality and their relationship to religious rules. The difference between law and morality lies in the way they are enforced. Law is backed by a threat of socially organized physical coercion; moral rules lack this sanction. The validity of religious rules is based upon Divine will; but if these rules are adopted by state law, their validity derives from the (secular) legislator. The notion of ‘rule of law’ has two different meanings, a formal and a substantive one. Formally, every state lives under the rule of law (Rechtsstaat, in German). The substantive notion relates to the content of the law, its evaluation from an ethical point of view, based on (subjective) ideological and political assumptions about the requirements of justice. In the context of law and religion, the rule of law is used to establish the correct solution to the conflict between the constitutional principles of individual and collective freedom of religion, freedom from religion and public order. The conflict between law and religion is particularly intense in Israel. The problem is to realize the constitutional program of establishing a state that is both Jewish and democratic-liberal. The traditional Orthodox concept of a Jewish state clashes with the modern notion of a liberal, secular-national state. The solution can and must be found in adapting the religious tradition to the modern reality of a Jewish state, composed of multicultural communities, within the framework of a liberal democracy.
Essential Role of IFT140 in Promoting Dentinogenesis
Authors: Li G. , Liu M. , Zhang S. , Wan H. , Zhang Q. , Yue R. , Yan X. , Wang X. , Wang Z. , Sun Y.
Published: December 2017

Primary cilia, with highly regulated cellular sensory functions, play key roles in tissue development and function maintenance. Intraflagellar transport 140 (IFT140) is a subunit of IFT complex A, which is specialized for retrograde transportation in cilia. Mutations of Ift140 are usually associated with syndromic ciliopathy and may cause isolated diseases such as retinal dystrophy, short ribs, and polycystic kidney. However, the role of IFT140 in tooth development has not been well investigated. In this study, a close relationship between IFT140 and dentin formation is disclosed. During tooth development, IFT140 was highly expressed in odontoblasts. To further understand the role of IFT140 in dentinogenesis, Ift140flox/flox/Osx-Cre mouse was generated. The dentin thickness of Ift140flox/flox/Osx-Cre mouse is thinner and the dentin formation is slower than that in control. In vitro, deletion of IFT140 in odontoblasts led to poor odontogenic differentiation, abnormal primary cilia, and decreased Sonic hedgehog signaling molecules. More important, due to loss of primary cilia in odontoblasts by IFT140 deletion, reparative dentin formation was impaired in a tooth-drilling model. These results suggest that cilia gene IFT140 is essential in promoting dentin formation and reparation.