bluuebunny/crossref_metadata_2025 huggingface dataset:
Septic Cavernous Sinus Thrombosis Following a Minor Head Injury: A Rare Cause of Medico‐Legal Death
Authors: Srettabunjong Supawon
Published: February 2018

Septic cavernous sinus thrombosis (SCST) is an uncommon consequence of head and face infection, but a rare complication after craniofacial fracture. In this case, SCST developed in a 13‐year‐old girl following a minor fall during volleyball, with impact and resulting abrasive contusion of the left forehead. She developed watery rhinorrhea, progressive headache, fever, nausea, vomiting, and left proptosis with blurred vision, and was admitted to hospital 3 days after injury. Drowsiness, high‐grade fever, severe headache, left ocular pain with marked periorbital swelling, and paralysis of extraocular eye movements developed. Computed tomography scan identified left sphenoid and ethmoid sinusitis, a posterior clinoid fracture, and septic cavernous sinus thrombosis. She died after 10 days of in‐hospital antibiotic therapy. Death was due to Staphylococcus aureus sepsis with septic pulmonary thromboemboli due to suppurative meningitis and cerebral infarction, due to SCST following apparently minor blunt head injury from an accidental fall.
A nodule endophytic Bacillus megaterium strain isolated from Medicago polymorpha enhances growth, promotes nodulation by Ensifer medicae and alleviates salt stress in alfalfa plants
Authors: Chinnaswamy A. , Coba de la Peña T. , Stoll A. , de la Peña Rojo D. , Bravo J. , Rincón A. , Lucas M.M. , Pueyo J.J.
Published: February 2018

A Gram‐positive, fast‐growing, endophytic bacterium was isolated from root nodules of Medicago polymorpha and identified as Bacillus megaterium. The isolate, named NMp082, co‐inhabited nodules with the symbiotic rhizobium Ensifer medicae. B. megaterium NMp082 contained nifH and nodD genes that were 100% identical to those of Ensifer meliloti, an unusual event that suggested previous lateral gene transfer from a different rhizobial species. Despite the presence of nodulation and nitrogen fixation genes, the endophyte was not able to form effective nodules; however, it induced nodule‐like unorganised structures in alfalfa roots. Axenic inoculation promoted plant growth in M. polymorpha, Medicago lupulina, Medicago truncatula and Medicago sativa, and co‐inoculation with E. medicae enhanced growth and nodulation of Medicago spp. plants compared with inoculation with either bacterium alone. B. megaterium NMp082 also induced tolerance to salt stress in alfalfa and Arabidopsis plants. The ability to produce indole acetic acid (IAA) and the 1‐aminocyclopropane‐1‐carboxylate (ACC) deaminase activity displayed by the endophyte in vitro might explain the observed plant growth promotion and salt stress alleviation. The isolate was also highly tolerant to salt stress, water deficit and to the presence of different heavy metals. The newly characterised endophytic bacterium possessed specific characteristics that point at potential applications to sustain plant growth and nodulation under abiotic stress.
The Future of Financial Reporting: Insights from Research
Authors: Barth Mary E.
Published: February 2018

Research offers insights that, if heeded and built upon, could improve financial reporting, thereby contributing to a more prosperous society. In particular, research suggests improvement could stem from greater use of fair value; a performance statement designed to reveal the information embedded in changes in fair value; better information to help investors assess the value of intangible assets; more specific information about risk and uncertainty; information that is unbiased, rather than conservative; acceptance of a degree of earnings management together with a determination of how much earnings management is acceptable; and a financial reporting package designed to convey information users need, which presumably is broader than today's financial statements.
Effects of alcohol intoxication on self‐reported drinking patterns, expectancies, motives and personality: a randomized controlled experimental study
Authors: Kuitunen‐Paul Sören , Obst Elisabeth , Schmidt Ruth , Sommer Christian , Kuitunen Paula T. , Wittchen Hans‐Ulrich , Zimmermann Ulrich S.
Published: February 2018

Alcohol intoxication may affect self‐reports of alcohol use and related constructs, such as impulsivity and dependence symptoms. Improved knowledge about potential systematic reporting biases induced by alcohol, e.g. through disinhibition, may be relevant for the assessment of intoxicated individuals both in clinical routine and research. We therefore randomly assigned 54 socially drinking males aged 18 to 19 without lifetime diagnosis of DSM‐IV alcohol dependence to one of two experimental arms: either placebo infusion at day 1 and alcohol infusion at day 2, or vice versa. The lab‐based intravenous alcohol infusion produced a constant blood alcohol level of 0.08 percent. On each day, participants completed the Alcohol Use Disorders Identification Test, as well as other questionnaires on alcohol expectancies, drinking motives and substance use‐related temperament traits. We found that alcohol significantly increased self‐reported expectancies (tension reduction) and motives (conformity; η2 = .16–.23), but we observed no effect of sequence, i.e. alcohol first versus placebo first (Pcorr ≥ .118). High baseline alcohol expectancies did not moderate alcohol effects (Pcorr ≥ .462). We conclude that moderate alcohol intoxication might not generally affect the reliability of self‐reported alcohol use, alcohol use problems and psychological concepts related to drinking behavior in young males without alcohol dependence. Future studies could examine larger, less selective and clinical samples for possible alcohol effects on self‐report measures related to alcohol consumption.
DRD2promoter methylation and measures of alcohol reward: functional activation of reward circuits and clinical severity
Authors: Bidwell L. Cinnamon , Karoly Hollis C. , Thayer Rachel E. , Claus Eric D. , Bryan Angela D. , Weiland Barbara J. , YorkWilliams Sophie , Hutchison Kent E.
Published: February 2018

Studies have identified strong associations between D2 receptor binding potential and neural responses to rewarding stimuli and substance use. Thus, D2 receptor perturbations are central to theoretical models of the pathophysiology of substance dependence, and epigenetic changes may represent one of the fundamental molecular mechanisms impacting the effects of alcohol exposure on the brain. We hypothesized that epigenetic alterations in the promoter region of the dopamine D2 receptor (DRD2) gene would be associated with cue‐elicited activation of neural reward regions, as well as severity of alcohol use behavior. The current study leveraged functional neuroimaging (fMRI) during an alcohol reward paradigm (n = 383) to test associations amongDRD2promoter methylation in peripheral tissue, signal change in the striatum during the presentation of alcohol cues, and severity of alcohol use disorder (AUD). Controlling for age,DRD2promoter methylation was positively associated with responses to alcohol cues in the right accumbens (partialr = 0.144,P = 0.005), left putamen (partialr = 0.133,P = 0.009), right putamen (partialr = 0.106,P = 0.039), left caudate (partialr = 0.117,P = 0.022), and right caudate (partialr = 0.133,P = 0.009), suggesting thatDRD2methylation was positively associated with robust activation in the striatum in response to reward cues.DRD2methylation was also positively associated with clinical metrics of AUD severity. Specifically, controlling for age,DRD2methylation was associated with Alcohol Use Disorders Identification Test total (partialr = 0.140,P = 0.002); Impaired Control Scale total (partialr = 0.097,P = 0.044) and Alcohol Dependence Scale total (partialr = 0.152,P = 0.001). Thus,DRD2methylation may be a critical mechanism linking D2 receptors with functional striatal brain changes and clinical severity among alcohol users.
Blue and yellow vane traps differ in their sampling effectiveness for wild bees in both open and wooded habitats
Authors: Hall Mark
Published: February 2018

Pan trapping is a common method for sampling wild bees, although the use of vane traps is growing globally. Despite this, few studies have tested the effectiveness of different coloured vane traps in attracting bees among different habitat types, and none exist in the southern hemisphere.

The present study sampled 192 sites (108 in wooded habitats and 84 in open habitats) within an agricultural region of southern Australia. Pairs of coloured vane traps (one blue and one yellow) were placed at each site for a period of seven days. Combined, 16 348 individuals were collected from four families, comprising 13 genera (21 subgenera) and 55 species.

Blue vane taps were most effective, sampling six times as many individuals as yellow vane traps and 96% of total species. Their effectiveness was consistent among open and wooded habitat types.

The present study highlights the efficacy of vane traps as a passive sampling technique for wild bees. An added benefit of this technique is that vane traps do not require pheromones or lethal agents.

A systematic sampling method best suited to the research question should be incorporated into studies of wild bees. For ecological census and population monitoring within multiple habitat types, the present study supports the use of blue vane taps as a major component of the sampling protocol.
Muscles and fascial elements of the antebrachium and manus of the African elephant (Loxodonta africana, Blumenbach 1797): starring comparative and functional considerations
Authors: Nagel R. M. , Forstenpointner G. , Soley J. T. , Weissengruber G. E.
Published: February 2018

The structure of the limbs of elephants is unusual among mammals. In African elephants (Loxodonta africana, Blumenbach 1797), the front limbs serve to support the greatest part of the body mass of the largest land animal. In this study, we present new and detailed anatomical data regarding muscular and specific fascial structures of the lower front limb which were examined by means of standard anatomical and histological techniques. The muscles and tendons of the forearm (antebrachium) and hand (manus) are tightly surrounded by thick, highly elastic fascial layers which fuse with the lacertus (lac.) fibrosus and the so‐called ligamentum (lig.) humeroulnare. A well‐developed musculus (m.) brachioradialis occupies the proximolateral aspect of the forearm and its tendon inserts together with the lac. fibrosus on the os carpi intermedium. The lac. fibrosus, the lig. humeroulnare and the m. flexor carpi radialis reveal a large proportion of elastic fibres. These three structures may play an important role in storing strain energy thus promoting energy‐saving locomotion. On the palmar aspect of the carpus, metacarpus and digits, short flexor, abductor, adductor, lumbricales and interossei muscles are present, whereas supinator muscles are absent in all specimens. The short muscles of the hand together with specific dorsal tendons enable precise movements of specific toes.
The relationships between depression, neuroticism, and attitudes (NDA model) in heroin abusers in Taiwan
Authors: Lee Kun‐Hua , Yen Cheng‐Fang
Published: February 2018

Background and Objectives

Heroin use is a severe problem worldwide. To develop more effective treatments for heroin abusers, a comprehensive psychosocial model of heroin use should be established and examined. We created and assessed a neuroticism, depression, attitudes, and heroin addiction (NDA) model.

Methods

In this cross‐sectional study, 234 patients undergoing methadone replacement treatment were recruited from psychiatric clinics. We used Structural Equation Modeling (SEM) to assess all for neuroticism, depression, and a positive outcome expectancy (POE) (attitudes).

Results

The full model had acceptable goodness‐of‐fit indices, but neuroticism was not significantly associated with a POE or heroin use. A reduced model that deleted insignificant paths had better goodness‐of‐fit indices, and neuroticism had indirect effects on heroin use via depression and a POE

Conclusions

Our findings provide evidence that depression, neuroticism, and POE affect heroin use. We also found that POE mediates between depression and heroin use. Despite the emotional regulation strategies recommended to help heroin abusers with depression to reduce the likelihood of their heroin use, teaching them with negative attitudes using heroin should also be considered when developing treatments for heroin abusers with depression.

Scientific Significance

Our findings provide a comprehensive mechanism of addiction that is integrated with emotion, cognition, and personality. Drug‐related beliefs and emotional regulation can be targeted to reduce the likelihood of relapse in abusers with higher levels of neuroticism. (Am J Addict 2018;27:139–143)
“Paying it forward” via satisfying a basic human need: The need for relatedness satisfaction mediates gratitude and prosocial behavior
Authors: Shiraki Yuma , Igarashi Tasuku
Published: February 2018

People who receive kindness tend to feel gratitude and act in a prosocial manner toward third persons (i.e., “paying it forward”). Combining the separate evidence that (a) gratitude leads to the formation of strong psychological bonds from a beneficiary to a benefactor and that (b) people become more prosocial toward strangers when the need for relatedness (NFR) is satisfied, two online experiments were conducted to examine if NFR satisfaction mediates the association between gratitude and prosocial behavior toward third persons. After evoking gratitude by recalling past experiences (Study 1) or writing a letter to someone (Study 2), participants were asked to make a donation from their remuneration for the experiment to a charity organization. As predicted, emotional manipulation promoted donation via feelings of gratitude and satisfied NFR. Implications of the current model for integrating previous findings are discussed.
Angioedema in chronic spontaneous urticaria is underdiagnosed and has a substantial impact: Analyses from ASSURE‐CSU
Authors: Sussman G. , Abuzakouk M. , Bérard F. , Canonica W. , Oude Elberink H. , Giménez‐Arnau A. , Grattan C. , Hollis K. , Hunter S. , Knulst A. , Lacour J.‐P. , Lynde C. , Marsland A. , McBride D. , Maurer M. , Nakonechna A. , Ortiz de Frutos J. , Reynolds M. , Sweeney C. , Tian H. , Weller K. , Wolin D. , Balp M.‐M.
Published: February 2018

Background

ASSURE‐CSU revealed differences in physician and patient reporting of angioedema. This post hoc analysis was conducted to evaluate the actual rate of angioedema in the study population and explore differences between patients with and without angioedema.

Methods

This international observational study assessed 673 patients with inadequately controlled chronic spontaneous urticaria (CSU). Physicians abstracted angioedema data from medical records, which were compared with patient‐reported data. Patients in the Yes‐angioedema category had angioedema reported in the medical record and a patient‐reported source. For those in the No‐angioedema category, angioedema was reported in neither the medical record nor a patient‐reported source. Those in the Misaligned category had angioedema reported in only one source. Statistical comparisons between Yes‐angioedema and No‐angioedema categories were conducted for measures of CSU activity, health‐related quality of life (HRQoL), productivity and healthcare resource utilization (HCRU). Regression analyses explored the relationship between Dermatology Life Quality Index (DLQI) score and angioedema, adjusting for important covariates.

Results

Among evaluable patients, 259 (40.3%), 173 (26.9%) and 211 (32.8%) were in the Yes‐angioedema, No‐angioedema and Misaligned category, respectively. CSU activity and impact on HRQoL, productivity, and HCRU was greater for Yes‐angioedema patients than No‐angioedema patients. After covariate adjustment, mean DLQI score was significantly higher (indicating worse HRQoL) for patients with angioedema versus no angioedema (9.88 vs 7.27, P < .001). The Misaligned category had similar results with Yes‐angioedema on all outcomes.

Conclusions

Angioedema in CSU seems to be under‐reported but has significant negative impacts on HRQoL, daily activities, HCRU and work compared with no angioedema.
Higher mortality of adults with asthma: A 15‐year follow‐up of a population‐based cohort
Authors: Lemmetyinen R. E. , Karjalainen J. V. , But A. , Renkonen R. L. O. , Pekkanen J. R. , Toppila‐Salmi S. K. , Haukka J. K.
Published: February 2018

Background

Higher all‐cause mortality in asthmatics has been shown previously. Polysensitization is associated with higher morbidity among asthmatic children, and allergic rhinitis and/or allergic conjunctivitis (AR/AC) are associated with higher morbidity in adult asthmatics. Little is known about the effect of AR/AC and other factors on mortality among adult asthmatics. The aim was to study mortality and its risk factors in adults with and without asthma.

Methods

We randomly selected 1648 asthmatics with age over 30 years from national registers and matched the asthma sample with one or two controls. Baseline information was obtained by a questionnaire in 1997, and the study population was linked with the death certificate information of Statistics Finland from 1997 to 2013. Overall and cause‐specific survival between the groups was compared in several adjusted models.

Results

During a mean follow‐up period of 15.6 years, 221 deaths among 1052 asthma patients and 335 deaths among 1889 nonasthmatics were observed. Cardiovascular diseases were the main cause of death in both groups. Asthma was associated with increased all‐cause mortality (adjusted HR 1.25; 95% CI 1.05‐1.49, P = .011) as well as mortality from chronic obstructive pulmonary disease (HR 12.0, 4.18‐34.2, P < .001) and malignant neoplasms of respiratory organs (HR 2.33, 1.25‐4.42, P = .008). Among asthmatics, smoking was associated with increased all‐cause mortality, and self‐reported AR/AC was associated with decreased mortality. Among nonasthmatics, smoking, and obesity were associated with increased all‐cause mortality, whereas female gender showed an association with a decreased risk.

Conclusions

Increased mortality among adult asthmatics was largely explained by the development of COPD, malignant respiratory tract neoplasms, and cardiovascular diseases. Smoking cessation is important for reduction in total mortality in both asthmatic and nonasthmatic adults. AR/AC was associated with decreased mortality only in asthmatics. Thus, studies in other populations of larger size are needed to explore further the nature of this association.
Association of STAT6 gene variants with food allergy diagnosed by double‐blind placebo‐controlled food challenges
Authors: van Ginkel C. D. , Pettersson M. E. , Dubois A. E. J. , Koppelman G. H.
Published: February 2018

This study describes the role of two STAT6 gene variants in food allergy using data of patients and their parents who underwent double‐blind placebo‐controlled food challenges (DBPCFCs). After quality control, 369 trios were analysed including 262 children (71.0%) with food allergy. Associations were tested by the Family based association test. The A alleles of both SNPs were associated with food allergy (P = .036 and P = .013 for rs324015 and rs1059513, respectively). Furthermore, these A alleles were associated with peanut allergy, higher sIgE levels to both peanut and cow's milk, more severe symptoms and higher eliciting doses during peanut and cow's milk DBPCFCs (all P < .05). In silico analysis indicates that the identified risk variants increase STAT6 expression which stimulates the differentiation of CD4 +  T cells to the Th2 subset. In conclusion, STAT6 variants may be involved in the pathophysiology of food allergy and their role seems to be independent of the allergenic food.
Comparison of three dehydration scales showed that they were of limited or no value for assessing small children with acute diarrhoea
Authors: Pomorska Dominika , Dziechciarz Piotr , Mduma Esto , Gidion Joshua , Falszewska Anna , Szajewska Hania
Published: February 2018

Aim

We explored the diagnostic accuracy of the clinical dehydration scale (CDS), the World Health Organization (WHO) scale and the Gorelick scale for assessing dehydration in children admitted to a Tanzanian referral hospital.

Methods

This was a prospective, observational study, carried out from April 2015 to January 2017 on children aged one month to five years admitted to the hospital with acute diarrhoea lasting less than five days. Before rehydration therapy, each patient's weight was recorded and the degree of dehydration was assessed based on the three scales. The reference standard was the percentage weight change between admission and discharge. The main outcomes were the sensitivity, specificity and positive and negative likelihood ratios (LRs) of the scales.

Results

Data from 124 eligible patients were available. The CDS showed limited value for ruling in cases with some dehydration (LR 1.9, 95% confidence interval 1.1–2.8), but was of no value in assessing no and moderate to severe dehydration. The WHO and Gorelick scales were of no value in evaluating any degree of dehydration.

Conclusion

The WHO and Gorelick dehydration scales were no use for assessing dehydration in small children, and the CDS was of limited use for predicting cases with some dehydration.
Entrapment of LTB protein in alginate nanoparticles protects against Enterotoxigenic Escherichia coli
Authors: Kordbacheh Emad , Nazarian Shahram , Hajizadeh Abbas , Sadeghi Davood
Published: February 2018

Vaccine delivery vehicles are just as important in vaccine efficiency. Through the progress in nanotechnology, various nanoparticles have been evaluated as carriers for these substances. Among them, alginate nanoparticles are a good choice because of their biodegradability, biocompatibility, ease of production, etc. In this study, feasibility of alginate nanoparticles (NPs) such as recombinant LTB from Enterotoxigenic Escherichia coli (ETEC) carrier was investigated. To do this, the eltb gene was cloned and expressed in E. coli BL21 (DE3) host cells, and a Ni‐NTA column purified the protein. NPs were achieved through ion gelation method in the presence of LTB protein and CaCl2 as the cross‐Linker and NPs were characterized physicochemically. Balb/C mice groups were immunized with LTB‐entrapped NPs or LTB with adjuvant and immunogenicity was assessed by evaluating IgG titer. Finally, the neutralization of antibodies was evaluated by GM1 binding and loop assays. LTB protein was expressed and efficiently entrapped into the alginate NPs. The size of NPs was less than 50 nm, and entrapment efficiency was 80%. Western blotting showed maintenance of the molecular weight and antigenicity of the released protein from NPs. Administration of LTB‐entrapped NPs stimulated antibody responses in immunized mice. Immunization induced protection against LT toxin of ETEC in ileal loops and inhibits enterotoxin binding to GM1‐gangliosides. Alginate NPs are also appropriate vehicle for antigen delivery purpose. Moreover because of their astonishing properties, they have the potential to serve as an adjuvant.
Expression of 14‐3‐3 sigma and eta proteins is unrelated to survival in metastatic high‐grade serous carcinoma
Authors: Davidson Ben , Holth Arild , Wang Zhihui , Hellsylt Ellen , Tropé Claes G. , Hetland Falkenthal Thea E. , Holm Ruth
Published: February 2018

The objective of this study was to analyze the expression and clinical role of 14‐3‐3 family proteins in high‐grade serous carcinoma (HGSC). Protein expression of 14‐3‐3 sigma (14‐3‐3σ) and 14‐3‐3 eta (14‐3‐3η) by immunohistochemistry was studied in 298 HGSC specimens (249 peritoneal, 49 pleural) and was analyzed for association with clinicopathologic parameters, chemoresponse and survival. The 14‐3‐3σ protein was diffusely (>75% of cells) expressed in 100% of carcinomas in analysis of a pilot series and was therefore not further analyzed. The 14‐3‐3η protein was expressed to a variable extent in 260/298 (87%) effusions. Higher 14‐3‐3η protein expression was significantly related to higher CA 125 levels at diagnosis (p = 0.004), but was unrelated to other clinicopathologic parameters, chemoresponse or survival. Analysis of the association between 14‐3‐3η and previously studied proteins regulating mitosis showed positive association with class III β‐tubulin expression (p = 0.025). The present study documents frequent expression of 14‐3‐3σ and 14‐3‐3η in HGSC effusions, but does not support a role for these proteins as prognostic markers or predictors of chemotherapy response in metastatic HGSC.
Gender‐Related Attitudes and Beliefs Predict White Women's Views of Candidates in the 2016 United States Presidential Election
Authors: Pahlke Erin , Bigler Rebecca S. , Patterson Meagan M.
Published: February 2018

White women's general failure to vote for Hillary Clinton in the 2016 United States presidential election (only 43% of White women did so) was largely unexpected. We tested the hypothesis that White women's gender‐related attitudes and beliefs, including their (i) feminist identification, (ii) views of societal gender discrimination, (iii) personal experiences with gender discrimination, and (iv) beliefs about female role models, were related to their levels of support for Hillary Clinton and her opponents (Sanders, Trump). A sample of White women (N = 314; 18–75 years, M = 32.71, SD = 13.37) recruited during June and July of 2016 from MTurk and college campuses completed surveys of their gender‐related attitudes and beliefs, as well as political preferences. Results indicated that women's gender‐related attitudes and beliefs predicted their views of both Clinton and Trump, after accounting for political ideology. For example, feminist identification was positively related to support for Clinton. Additionally, stronger endorsement of the notion that societal gender discrimination persists in the United States predicted both more favorable ratings of Clinton and less favorable ratings of Trump. More frequent personal experiences with discrimination, in contrast, predicted weaker support for Clinton.
Economic Anxieties Undermine Support for Female (but Not Male) Political Candidates
Authors: Lei Ryan F. , Bodenhausen Galen V.
Published: February 2018

Are female politicians disadvantaged by adverse economic conditions in ways their male counterparts are not? To examine this issue, we had participants read a news article about the current economic situation. The article emphasized either economic stability or volatility. Afterward, they evaluated an advertisement for either a female or a male candidate for the U.S. Senate. Exposure to news depicting economic instability caused devaluation of the female but not the male candidate. A second study provided a direct replication of this finding with a larger sample.  An omnibus analysis (N = 535) showed that this devaluation pattern occurred primarily among male participants. Study 2 also examined whether gender stereotypes play a role in this process.  Indeed, men's confidence in the female candidate's ability to handle stereotypically masculine issues decreased under economic instability and this tendency mediated their devaluation of the female candidate.
Bayesian Enhancement Two-Stage Design for Single-Arm Phase II Clinical Trials with Binary and Time-to-Event Endpoints
Authors: Shi Haolun , Yin Guosheng
Published: February 2018

Simon's two-stage design is one of the most commonly used methods in phase II clinical trials with binary endpoints. The design tests the null hypothesis that the response rate is less than an uninteresting level, versus the alternative hypothesis that the response rate is greater than a desirable target level. From a Bayesian perspective, we compute the posterior probabilities of the null and alternative hypotheses given that a promising result is declared in Simon's design. Our study reveals that because the frequentist hypothesis testing framework places its focus on the null hypothesis, a potentially efficacious treatment identified by rejecting the null under Simon's design could have only less than 10% posterior probability of attaining the desirable target level. Due to the indifference region between the null and alternative, rejecting the null does not necessarily mean that the drug achieves the desirable response level. To clarify such ambiguity, we propose a Bayesian enhancement two-stage (BET) design, which guarantees a high posterior probability of the response rate reaching the target level, while allowing for early termination and sample size saving in case that the drug's response rate is smaller than the clinically uninteresting level. Moreover, the BET design can be naturally adapted to accommodate survival endpoints. We conduct extensive simulation studies to examine the empirical performance of our design and present two trial examples as applications.
Time trends and occupational variation in the incidence of testicular cancer in the Nordic countries
Authors: Ylönen Outi , Jyrkkiö Sirkku , Pukkala Eero , Syvänen Kari , Boström Peter J.
Published: February 2018

Objective

To describe the trends and occupational variation in the incidence of testicular cancer in the Nordic countries utilising national cancer registries, NORDCAN (NORDCAN project/database presents the incidence, mortality, prevalence and survival from >50 cancers in the Nordic countries) and NOCCA (Nordic Occupational Cancer) databases.

Patients and Methods

We obtained the incidence data of testicular cancer for 5‐year periods from 1960–1964 to 2000–2014 and for 5‐year age‐groups from the NORDCAN database. Morphological data on incident cases of seminoma and non‐seminoma were obtained from national cancer registries. Age‐standardised incidence rates (ASR) were calculated per 100 000 person‐years (World Standard). Regression analysis was used to evaluate the annual change in the incidence of testicular cancer in each of the Nordic countries. The risk of testicular cancer in different professions was described based on NOCCA information and expressed as standardised incidence ratios (SIRs).

Results

During 2010–2014 the ASR for testicular cancer varied from 11.3 in Norway to 5.8 in Finland. Until 1998, the incidence was highest in Denmark. There has not been an increase in Denmark and Iceland since the 1990s, whilst the incidence is still strongly increasing in Norway, Sweden, and Finland. There were no remarkable changes in the ratio of seminoma and non‐seminoma incidences during the past 50 years. There was no increase in the incidences in children and those of pension age. The highest significant excess risks of testicular seminoma were found in physicians (SIR 1.48, 95% confidence interval [CI] 1.07–1.99), artistic workers (SIR 1.47, 95% CI 1.06–1.99) and religious workers etc. (SIR 1.33, 95% CI 1.14–1.56). The lowest SIRs of testicular seminoma were seen amongst cooks and stewards (SIR 0.56, 95% CI 0.29–0.98), and forestry workers (SIR 0.64, 95% CI 0.47–0.86). The occupational category of administrators was the only one with a significantly elevated SIR for testicular non‐seminoma (SIR 1.21, 95% CI 1.04–1.42). The only SIRs significantly <1.0 were seen amongst engine operators (SIR 0.60, 95% CI 0.41–0.84) and public safety workers (SIR 0.67, 95% CI 0.43–0.99).

Conclusions

There have always been differences in the incidence of testicular cancer between the Nordic countries. There is also some divergence in the incidences in different age groups and in the trends of the incidence. The effect of occupation‐related factors on incidence of testicular cancer is only moderate. Our study describes the differences, but provides no explanation for this variation.
A multiproxy record of the Younger Holsteinian Oscillation (YHO) in the Ossówka profile, eastern Poland
Authors: Nitychoruk Jerzy , Bińka Krzysztof , Sienkiewicz Elwira , Szymanek Marcin , Chodyka Marta , Makos Michał , Ruppert Hans , Tudryn Alina
Published: February 2018

The laminated lacustrine succession at Ossówka in eastern Poland, which is largely the equivalent of MIS 11c, is amongst the best‐developed sites in Europe that cover this time period. Close inspection of the depth interval between 35.0 and 42.5 m in a 55‐m‐long core shows an environmental crisis at a depth of 40.95 m that lasted approximately 800 years and resulted in almost complete extinction of fir (Abies) from the communities existing at that time. Geochemical analyses reveal a simultaneous increase in sulphur in the deposits and a change in stable carbon and oxygen isotope ratios towards higher values, as well as a significant increase in the thickness of the laminae (up to 5 mm). Diatom studies show a clear increase in benthic diatoms in this interval, implying a decrease in water level. However, the predominance of such forms was probably caused by the elimination of planktonic diatoms by invasive blooms of Tetraedron, rather than lower lake levels, evidence of which was not noted in the pollen spectra. Hence, all these changes in the lake may have been triggered by the destruction of fir trees, the gradual decomposition of dead trunks and some inconspicuous geomorphological disturbances caused by wind throw. They resulted in a supply of micronutrients to the basin, an increase in varve thickness and rapid oscillations in the abundance and composition of algae and changes in the geochemical status of the lake. Rapid and significant drops in winter temperatures appear to be responsible for the extinction of fir. Alternatively, late frost in spring or hot and dry summers may have affected microsporophyll growth and the fir physiology as known from extant Abies populations. This environmental crisis, which is termed the Younger Holsteinian Oscillation (YHO), is noted at only a few sites. At Dethlingen (Germany), where hornbeam communities disappear at that time, a drop in summer temperatures is suggested to have been the driving force. We suggest that, at Ossówka, a drop in winter temperatures, late frost, or summer drought at the very start of the YHO are possible causes of the near‐extinction of fir.
Submarine sediment routing over a blocky mass‐transport deposit in the Espírito Santo Basin, SE Brazil
Authors: Ward Nicholas I. P. , Alves Tiago M. , Blenkinsop Thomas G.
Published: February 2018

The control of slide blocks on slope depositional systems is investigated in a high‐quality 3D seismic volume from the Espírito Santo Basin, SE Brazil. Seismic interpretation and statistical methods were used to understand the effect of differential compaction on strata proximal to the headwall of a blocky mass‐transport deposit (MTD), where blocks are large and undisturbed (remnant), and in the distal part of this same deposit. The distal part contains smaller rafted blocks that moved and deformed with the MTD. Upon their emplacement, the positive topographic relief of blocks created a rugged seafloor, confining sediment pathways and creating accommodation space for slope sediment. In parallel, competent blocks resisted compaction more than the surrounding debrite matrix during early burial. This resulted in differential compaction between competent blocks and soft flanking strata, in a process that was able to maintain a rugged seafloor for >5 Ma after burial. Around the largest blocks, a cluster of striations associated with a submarine channel bypassed these obstructions on the slope and, as a result, reflects important deflection by blocks and compaction‐related folds that were obstructing turbidite flows. Log‐log graphs were made to compare the width and height of different stratigraphic elements; blocks, depocentres and channels. There is a strong correlation between the sizes of each element, but with each subsequent stage (block–depocentre–channel) displaying marked reductions in height. Blocky MTDs found on passive margins across the globe are likely to experience similar effects during early burial to those documented in this work.
In vivo optical imaging of cancer cell function and tumor microenvironment
Authors: Imamura Takeshi , Saitou Takashi , Kawakami Ryosuke
Published: February 2018

In vivo optical imaging using fluorescence and bioluminescence is superior to other methods in terms of spatiotemporal resolution and specificity, and represents a new technology for comprehensively studying living organisms in a less invasive way. Nowadays, it is an indispensable technology for studying many aspects of cancer biology, including dynamic invasion and metastasis. In observations of fluorescence or bioluminescence signals in a living body, various problems were caused by optical characteristics such as absorption and scattering and, therefore, observation of deep tissue was difficult. Recent developments in techniques for observation of the deep tissues of living animals overcame this difficulty by improving bioluminescent proteins, fluorescent proteins, and fluorescent dyes, as well as detection technologies such as two‐photon excitation microscopy. In the present review, we introduce these technological developments and in vivo application of bioluminescence and fluorescence imaging, and discuss future perspectives on the use of in vivo optical imaging technology in cancer research.
Forty years of referrals and outcomes to a UK Child Development Centre (CDC): Has demand plateaued?
Authors: Williams A. N. , Mold B. , Kilbey L. , Naganna P.
Published: February 2018

Aims

To explore 40 years of Child Development Centre (CDC) activity and outcomes at Northampton General Hospital 1974–2014.

Methods

The study comprises 3 data sets: a published report from 1974 to 1999, an internal audit from 2001 to 2004, and more recent data collected from 2005 to 2014. The medical notes of all children who were assessed by the CDC in 2014 were reviewed, along with referral data collected by the CDC manager from this year and the preceding 10 years.

Results

From January 1, 1974 to December 31, 2014, 3,786 children were assessed. The male to female ratio is 2.8:1 from 2005 to 2014. Referrals for behavioural difficulties increased from 10% (10/100 referrals) in 1999–2004 to 17.8% (18/101 referrals) in 2014. Similarly, referrals for social and communication problems, “interaction” increased two and a half fold from 10% (10/100 referrals) in 1999–2004 to 26.7% (27/101 referrals) in 2014. Between 2004 and 2014, numbers of referrals for “developmental delay” halved (22.2% to 12%).

Conclusion

We are aware of no other comparable extant UK CDC database. Services should plan for a referral rate of 6.5 per 1,000 preschool children. Between 1974 and 2014, there has clearly been a change in recorded assessment outcomes. From the mid‐1980s, this reflects the change to a preschool assessment role and a shift away from purely educational outcome to include medical conditions.

Covering 1974–2014, we demonstrate a clear increase in the number of referrals together with an increasing demand for assessments for social interaction and behavioural difficulties. This reflects the increased awareness of these neurodevelopmental difficulties and the changing diagnostic criteria which will now more likely result in an Autistic Spectrum Disorder diagnosis than previously. Together, these two features are most likely to have considerable implications for service development within Child Development Centres (CDCs) and Child Development Teams (CDTs).
Factors associated with delayed infant immunization in a nationally representative cohort study
Authors: Homel J. , Edwards B.
Published: February 2018

Background

Many children in developed countries do not receive recommended vaccines on time. However, knowledge about factors related to timeliness remains limited. Quantifying the relative impact of parental attitudes compared with socio‐demographic factors for delayed immunization would inform policy responses.

Methods

Participants in the nationally representative Longitudinal Study of Australian Children were matched with their vaccination histories in the Australian Childhood Immunisation Register (N = 4,121). Information about the children and their families were collected in face‐to‐face interviews in 2003–2004. We considered whether children had completed the primary course for each recommended antigen due by 6 months old. Children were categorized as either fully immunized, delayed, or totally non‐immunized. The outcome was examined using logistic regression. Population attributable fractions were estimated for key predictors.

Results

Delayed immunization was significantly associated with indicators of social disadvantage as well as parental disagreement with immunization. Attributable fractions for delayed immunization included lone motherhood (3.8%; 95% confidence interval CI [0.8, 6.7]), larger family size (39.5%; 95% CI [31.2, 46.8]), residential mobility (3.3%; 95% CI [0.1, 6.5]), lack of private hospital insurance (9.4%; 95% CI [0.7, 17.3]), a medical condition in the child (2.0%; 95% CI [0.2, 3.9]), and parental disagreement with immunization (2.1%; 95% CI [0.3, 3.9]).

Conclusions

Parental attitudes accounted for a relatively small percentage of delayed infant immunization. In contrast, many children who did not receive vaccines on time were characterized by social disadvantage, especially larger family size. Researchers and policy‐makers should consider how to make timely immunization easier for busy parents.
Investigating societal determinants of oral health—Opportunities and challenges in multilevel studies
Authors: Singh Ankur , Harford Jane , Peres Marco A.
Published: February 2018

The high prevalence of oral diseases and the persistent nature of socioeconomic inequalities in oral health outcomes across societies presents a significant challenge for public health globally. A debate exists in epidemiology on the merits of investigating population variations in health and its determinants over studying individual health and its individual risk factors. The choice of analytical unit for health outcomes at the population level has policy implications and consequences for the causal understanding of population‐level variations in health/disease. There is a lack of discussion in oral epidemiology on the relevance of studying population variations in oral health. Evidence on the role of societal factors in shaping variations in oral health at both the individual level and the population level is also mounting. Multilevel studies are increasingly applied in social epidemiology to address hypotheses generated at different levels of social organization, but the opportunities offered by multilevel approaches are less applied for studying determinants of oral health at the societal level. Multilevel studies are complex as they aim to examine hypotheses generated at multiple levels of social organization and require attention to a range of theoretical and methodological aspects from the stage of design to analysis and interpretation. This discussion study aimed to highlight the value in studying population variations in oral health. It discusses the opportunities provided by multilevel approaches to study societal determinants of oral health. Finally, it reviews the key methodological aspects related to operationalizing multilevel studies of societal determinants of oral health.
Heterozygous aggrecan variants are associated with short stature and brachydactyly: Description of 16 probands and a review of the literature
Authors: Sentchordi‐Montané Lucía , Aza‐Carmona Miriam , Benito‐Sanz Sara , Barreda‐ Bonis Ana C. , Sánchez‐Garre Consuelo , Prieto‐Matos Pablo , Ruiz‐Ocaña Pablo , Lechuga‐Sancho Alfonso , Carcavilla‐Urquí Atilano , Mulero‐Collantes Inés , Martos‐Moreno Gabriel A. , del Pozo Angela , Vallespín Elena , Offiah Amaka , Parrón‐Pajares Manuel , Dinis Isabel , Sousa Sergio B. , Ros‐Pérez Purificación , González‐Casado Isabel , Heath Karen E.
Published: February 2018

Objective

Mutations in the aggrecan gene (ACAN) have been identified in two autosomal dominant skeletal dysplasias, spondyloepiphyseal dysplasia, Kimberley type (SEDK), and osteochondritis dissecans, as well as in a severe recessive dysplasia, spondyloepimetaphyseal dysplasia, aggrecan type. Next‐generation sequencing (NGS) has aided the identification of heterozygous ACAN mutations in individuals with short stature, minor skeletal defects and mild facial dysmorphisms, some of whom have advanced bone age (BA), poor pubertal spurt and early growth cessation as well as precocious osteoarthritis.

Design and methods

This study involves clinical and genetic characterization of 16 probands with heterozygous ACAN variants, 14 with short stature and mild skeletal defects (group 1) and two with SEDK (group 2). Subsequently, we reviewed the literature to determine the frequency of the different clinical characteristics in ACAN‐positive individuals.

Results

A total of 16 ACAN variants were located throughout the gene, six pathogenic mutations and 10 variants of unknown significance (VUS). Interestingly, brachydactyly was observed in all probands. Probands from group 1 with a pathogenic mutation tended to be shorter, and 60% had an advanced BA compared to 0% in those with a VUS. A higher incidence of coxa valga was observed in individuals with a VUS (37% vs 0%). Nevertheless, other features were present at similar frequencies.

Conclusions

ACAN should be considered as a candidate gene in patients with short stature and minor skeletal defects, particularly those with brachydactyly, and in patients with spondyloepiphyseal dysplasia. It is also important to note that advanced BA and osteoarticular complications are not obligatory conditions for aggrecanopathies/aggrecan‐associated dysplasias.
Expanding the histopathological spectrum of CFL2‐related myopathies
Authors: Fattori F. , Fiorillo C. , Rodolico C. , Tasca G. , Verardo M. , Bellacchio E. , Pizzi S. , Ciolfi A. , Fagiolari G. , Lupica A. , Broda P. , Pedemonte M. , Moggio M. , Bruno C. , Tartaglia M. , Bertini E. , D'Amico A.
Published: February 2018

Congenital myopathies (CMs) caused by mutation in cofilin‐2 gene (CFL2) show phenotypic heterogeneity ranging from early‐onset and rapid progressive forms to milder myopathy. Muscle histology is also heterogeneous showing rods and/or myofibrillar changes. Here, we report on three new cases, from two unrelated families, of severe CM related to novel homozygous or compound heterozygous loss‐of‐function mutations in CFL2. Peculiar histopathological changes showed nemaline bodies and thin filaments accumulations together to myofibrillar changes, which were evocative of the muscle findings observed in Cfl2−/− knockout mouse model.
Impact of hand eczema on quality of life: metropolitan versus non‐metropolitan areas
Authors: Nørreslet Line B. , Agner Tove , Sørensen Jennifer A. , Ebbehøj Niels E. , Bonde Jens P. , Fisker Maja H.
Published: February 2018

Background

An inverse relationship between disease severity and health‐related quality of life (HR‐QoL) in patients with hand eczema is well established, but modifying effects of demographic variables have been less well studied.

Objective

To identify the influence of metropolitan versus non‐metropolitan residence on the relationship between disease severity and HR‐QoL in patients with occupational hand eczema.

Methods

The city of Copenhagen and the rest of Zealand were defined as metropolitan and non‐metropolitan areas, respectively. Participants were 773 persons with occupational hand eczema. A questionnaire on the severity of hand eczema and HR‐QoL was sent to all participants.

Results

The odds for reporting moderate to high severity of occupational hand eczema were significantly lower in the metropolitan population than in the non‐metropolitan population [odds ratio (OR): 0.42; 95%CI: 0.23–0.75], whereas low dermatology‐related quality of life was more prevalent in metropolitan than in non‐metropolitan patients (OR: 1.31; 95%CI: 0.83–2.05), indicating that hand eczema had a more pronounced negative effect in metropolitan patients, in spite of less severe eczema.

Conclusion

Our data indicate that area of residence has a modifying effect on the relationship between disease severity and HR‐QoL, with a more negative impact on HR‐QoL in metropolitan than in non‐metropolitan areas. This information is important with respect to fully appreciating the burden of occupational hand eczema.