bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiologically based pharmacokinetic modelling to predict exposure differences in healthy volunteers and subjects with renal impairment: Ceftazidime case study
Authors: Zhou Li , Tong Xiao , Sharma Pradeep , Xu Hongmei , Al‐Huniti Nidal , Zhou Diansong
Published: February 2019

Ceftazidime is a widely used β‐lactam antibiotic and almost entirely excreted via glomerular filtration in kidney. The objective of this analysis was to assess the ability of physiologically based pharmacokinetic (PBPK) model to predict ceftazidime exposure in healthy volunteers and subjects with renal impairment. A full PBPK model of ceftazidime was developed using physiochemical properties and clinical data. The total clearance of 115 mL/min and renal clearance of 100 mL/min were obtained from ceftazidime package insert. Healthy and chronic kidney disease (CKD) populations were applied for sampling of virtual subjects. The established PBPK model predicted mean plasma AUCinf were 138.5 ± 19.6, 230.7 ± 22.2, 369.3 ± 53.1 and 561.8 ± 92.4 h µg/mL in healthy, mild, moderate and severe renal impairment subjects, respectively, after administration of 1 g ceftazidime intravenous bolus dose. The predicted values were in close agreement with the weighted mean of the five reported clinical studies. The exposure was slightly under predicted in subjects with severely impaired renal function, but still within 1.5‐fold range. The concentration‐time profiles of ceftazidime were also well captured in healthy volunteers and subjects with renal impairment. The developed PBPK model along with systems pharmacokinetics (PK) (renal impaired populations) well predicted the ceftazidime exposure. PBPK models verified with clinical study in healthy volunteers could be potentially applied to predict PK and recommend dose adjustment for CKD patients.
What motivates academic dishonesty in students? A reinforcement sensitivity theory explanation
Authors: Bacon Alison M. , McDaid Chloe , Williams Natasha , Corr Philip J.
Published: February 2019

Background

Academic dishonesty (AD) is an increasing challenge for universities worldwide. The rise of the Internet has further increased opportunities for students to cheat.

Aims

In this study, we investigate the role of personality traits defined within Reinforcement Sensitivity Theory (RST) as potential determinants of AD. RST defines behaviour as resulting from approach (Reward Interest/reactivity, goal‐drive, and Impulsivity) and avoidance (behavioural inhibition and Fight–Flight–Freeze) motivations. We further consider the role of deep, surface, or achieving study motivations in mediating/moderating the relationship between personality and AD.

Sample

A sample of UK undergraduates (N = 240).

Method

All participants completed the RST Personality Questionnaire, a short‐form version of the study process questionnaire and a measure of engagement in AD, its perceived prevalence, and seriousness.

Results

Results showed that RST traits account for additional variance in AD. Mediation analysis suggested that GDP predicted dishonesty indirectly via a surface study approach while the indirect effect via deep study processes suggested dishonesty was not likely. Likelihood of engagement in AD was positively associated with personality traits reflecting Impulsivity and Fight–Flight–Freeze behaviours. Surface study motivation moderated the Impulsivity effect and achieving motivation the FFFS effect such that cheating was even more likely when high levels of these processes were used.

Conclusions

The findings suggest that motivational personality traits defined within RST can explain variance in the likelihood of engaging in dishonest academic behaviours.
Clinical relevance of pulmonary vasculature involvement in sickle cell disease
Authors: Carstens German R. , Paulino Bianca B. A. , Katayama Edgard H. , Amato‐Lourenço Luis F. , Fonseca Guilherme H. , Souza Rogerio , Aiello Vera D. , Mauad Thais
Published: February 2019

Pulmonary complications are frequent in patients with sickle cell disease (SCD), but few studies have described lung pathology in SCD. We studied the lung tissue of 30 deceased SCD patients (1994–2012). Demographics, genotype, clinical characteristics, cause of death and associated conditions are presented. We quantified the presence of pulmonary arterial changes, thrombosis and venous thickening. Alveolar capillary abnormalities were demonstrated using CD34 expression and confocal microscopy. Autopsy and echocardiography reports were reviewed to classify heart abnormalities. Tissue expression of markers of endothelial activation (vascular cell adhesion molecule 1, intercellular adhesion molecule 1 and vascular endothelial growth factor) was quantified in pulmonary vessels. Median age was 33 years; genotype was SS in 19, SC in 7 and Sβ in 4, and there were 18 males. Hypertensive arterial changes were present in 76% of the patients, recent thrombosis in 80% and old thrombosis in 43%. Venous thickening was present in 23% and pulmonary capillary haemangiomatosis foci in 87%. Ten percent of the patients presented right ventricular hypertrophy. There was no increased expression of endothelial activation markers when compared to controls. SCD affects the whole pulmonary vascular tree and reflects the multiple burden on lung vasculature imposed by the disease upon time.
Environmental conditions in northwestern Russia during MIS 5 inferred from the pollen stratigraphy in a sediment core from Lake Ladoga
Authors: Andreev Andrei A. , Shumilovskikh Lyudmila S. , Savelieva Larisa A. , Gromig Raphael , Fedorov Grigory B. , Ludikova Anna , Wagner Bernd , Wennrich Volker , Brill Dominik , Melles Martin
Published: February 2019

Lake Ladoga hosts preglacial sediments, although the Eurasian ice sheet overrode the area during the LGM. These sediments were first discovered by a seismic survey and are investigated using a 22.75‐m‐long core. Its upper 13.30 m comprise Holocene and Lateglacial sediments separated from the lower 11.45 m of preglacial sediments by a hiatus. They consist of highly terrigenous lacustrine sediments, which according to OSL dating, were deposited during an early stage of the last ice age (MIS 5). The palynological data allow a first reconstruction of the Early Weichselian environmental history for northwestern Russia. Birch and alder forests with broad‐leaved taxa dominated during MIS 5d (c. 118–113 ka), suggesting a climate more favourable than in the Holocene. A high content of well‐sorted sands and poorly preserved palynomorphs indicates a shallow‐water environment at least temporarily. More fine‐grained sediments and better preserved organic remains suggest deeper water environments at the core location during MIS 5c (c. 113–88 ka). Pine and spruce became dominant, while broad‐leaved taxa started to disappear, especially after c. 90 ka, pointing to a gradual climate cooling. An increase in open herb‐dominated habitats at the beginning of MIS 5b (c. 88–86 ka) reflects a colder and dryer climate. However, later (c. 86–82 ka) pine and spruce again became more common. Birch and alder forests dominated in the area c. 82–80 ka (beginning of MIS 5a). Although open treeless habitats also became more common at this time, a slight increase in hazel may point to somewhat warmer climate conditions coinciding with the beginning of MIS 5a. The studied sediments also contain numerous remains of freshwater algae and cysts of marine and brackish‐water dinoflagellates and acritarchs documenting that the present lake basin was part of a brackish‐water basin during the Early Weichselian, probably as a gulf of the Pre‐Baltic Sea.
Dynamic formation of preferential trade agreements: The role of flexibility
Authors: Lake James
Published: February 2019

In practice, free trade agreements (FTAs) vastly outnumber customs unions (CUs). Nevertheless, the literature traditionally views CUs as optimal for members because CU members coordinate external tariffs. I show that a dynamic FTA flexibility benefit can help explain the prevalence of FTAs: individual FTA members have the flexibility to form their own future FTAs whereas CU members must jointly engage in future CU formation. I show how the relative prevalence of FTAs versus CUs depends on the structure of market size asymmetry across countries and use these predictions to shed some light on FTA versus CU formation in Europe and South America.
The influence of wound closure on graft stability: An in vitro comparison of different bone grafting techniques for the treatment of one‐wall horizontal bone defects
Authors: Mertens Christian , Braun Sebastian , Krisam Johannes , Hoffmann Jürgen
Published: February 2019

Objectives

The aim of this preclinical study was to analyze and compare different grafting techniques with respect to volume stability after wound closure.

Materials and Methods

Four different grafting techniques were evaluated in vitro for volume stability in a one‐wall horizontal defect configuration. Group 1: guided bone regeneration (GBR) with collagen membrane, particulated xenograft; group 2: GBR with collagen membrane, particulated xenograft, pins; group 3: GBR with titanium‐reinforced membrane, particulated xenograft, pins; group 4: autogenous block graft, particulated xenograft, collagen membrane. Cone beam computed tomography scans were performed before and after wound closure, and the horizontal bone dimensions were analyzed for stability at 0‐5 mm apical to the implant shoulder (H0‐H5).

Results

At H0‐H2, wound closure induced a statistically significant change in bone dimensions in groups 1 and 2. In group 3, only the change in H0 was significant, and for group 4, only H2 was significant.

Conclusion

Wound closure has a significant impact on graft stability in a one‐wall horizontal defect configuration. GBR with additional membrane fixation showed better results than without. Titanium‐reinforced membranes and autogenous blocks showed significantly greater volume stability than GBR with collagen membrane, especially in the coronal portion.
Preadmission use of antidepressants and risk of complications and death after colorectal cancer surgery: a nationwide population‐based cohort study
Authors: Lycke K. D. , Christiansen C. F. , Lund J. L. , Iversen L. H. , Nørgaard M.
Published: February 2019

Aim

Few studies have evaluated how preadmission use of antidepressants affects outcomes in colorectal cancer (CRC) patients after they have undergone surgery. Therefore, our aim is to examine whether preadmission use of antidepressants increased the risk of complications and death in patients who underwent CRC surgery.

Method

Using the Danish Colorectal Cancer Group Database we identified patients who underwent CRC surgery in Denmark from 2005 to 2012. We identified prescriptions for antidepressants redeemed within 1 year prior to surgery and categorized patients as current users (≤ 90 days), former users (91–365 days) and nonusers. All patients were followed from surgery to 30 days thereafter or to death. We calculated 30‐day rates of complications, intensive care unit (ICU) admission and mortality and compared these between users and nonusers using logistic and Cox regression adjusting for potential confounders.

Results

Of 27 374 patients, 8.9% were current users and 3.0% were former users. Antidepressant users were older and had more comorbidity but a similar cancer stage. Compared with nonusers, current users had a higher risk of postoperative reoperation [adjusted odds ratio (aORs) = 1.15 (95% CI 1.02–1.30)], medical complications [aORs = 1.41 (95% CI 1.25–1.60)] and increased ICU admission rate [adjusted hazard ratio (aHR) = 1.32 (95% CI 1.21–1.45)]. The 30‐day mortality was 11.4% for current users, 9.1% for former users and 6.2% for nonusers [aHR = 1.34 (95% CI 1.17–1.53) for current vs nonusers].

Conclusion

Patients with preadmission use of antidepressants had a higher risk of complications and ICU admission, and higher 30‐day mortality following CRC surgery than nonusers.
A randomized controlled trial on the effect of topical phenytoin 2% on wound healing after anal fistulotomy
Authors: Sanad A. , Emile S. , Thabet W. , Ellaithy R.
Published: February 2019

Aim

Laying open fistulotomy is the standard treatment for simple anal fistula. However, healing of the resultant anal wound may be prolonged and may adversely affect a patient's lifestyle and work. This randomized trial aimed to assess the effect of topical phenytoin 2% powder spray on healing of the anal wound following fistulotomy.

Method

Adult patients with simple anal fistula who underwent anal fistulotomy were divided into two equal groups: group I applied topical phenytoin 2% powder spray on the anal wound regularly with sitz baths until complete healing was confirmed clinically and group II had regular sitz baths only. The primary outcome of the study was time to complete wound healing. Secondary outcomes were postoperative pain, complications, time to return to work and impact on lifestyle.

Results

Sixty patients (50 of whom were men) with a mean age of 41.4 ± 12.5 years were included. Both groups had comparable pain scores at 1 week after surgery (1 ± 0.83 vs 0.86 ± 0.81; P = 0.51). The duration to complete wound healing was 41.2 ± 2.4 days in group I and 42 ± 2.5 days in group II (mean ± SD, P = 0.21). The time to return to work was 13.5 ± 2.8 days in group I and 14.1 ± 2.6 days in group II (mean ± SD, P = 0.39). No significant differences were noted between the two groups with regard to postoperative complications or impact on lifestyle.

Conclusion

The use of topical phenytoin 2% powder spray did not promote wound healing, relieve postoperative pain or accelerate patient recovery after anal fistulotomy for simple anal fistula.
Barriers and facilitators to switching from smoking to vaping: Advice from vapers
Authors: Morphett Kylie , Weier Megan , Borland Ron , Yong Hua‐Hie , Gartner Coral
Published: February 2019

Introduction and Aims

Information available to consumers about nicotine vaping products varies according to the regulatory environment. A common information source in Australia, where nicotine vaping products are highly regulated, is advice from vapers. The aim of this study was to report on what advice current vapers would give to someone new to vaping.

Design and Methods

Australian vapers were recruited in 2016 via the International Tobacco Control Four‐Country Smoking and Vaping survey of smokers and ex‐smokers, as well as a separate recruitment process that targeted vapers. A total of 384 of 559 eligible participants responded to an open‐ended question about barriers to switching from smoking to vaping, and what advice they would give to new vapers.

Results

While some participants reported switching from smoking to vaping easily, others described an adjustment period. Difficulties included learning about technical aspects of nicotine vaping products, finding the ‘right’ combination of device and liquid, and accessing nicotine liquid given that it cannot legally be sold. Many accounts of satisfaction with quitting smoking and improved health were provided.

Discussion and conclusions

Advice from current vapers is likely to be particularly influential in Australia, where information about vaping is not easily available from health organisations or official government sources. This research shows that advice to new vaper centres around experimentation with devices and flavours and finding trustworthy suppliers of nicotine liquid. It provides an insight into the initial challenges associated with switching from smoking to nicotine vaping products in environments where access to nicotine liquid is highly restricted.
Childhood disintegrative disorder: part of the autism spectrum?
Authors: Rosman N Paul
Published: February 2019

This commentary is on the systematic review by Mehra et al. on pages 523–534 of this issue.
Mental health literacy programs for school teachers: A systematic review and narrative synthesis
Authors: Yamaguchi Satoshi , Foo Jerome C. , Nishida Asuka , Ogawa Sayoko , Togo Fumiharu , Sasaki Tsukasa
Published: February 2019

Aim

The prevalence of mental disorders increases sharply during adolescence. Therefore, school teachers are in a good position to provide initial assistance to students with mental health problems. Although effects of a number of mental health literacy programs aimed at teachers have been reported, they have not yet been reviewed in a systematic manner. This study conducted a systematic review of the effectiveness of mental health literacy programs for teachers.

Methods

PubMed, PsycINFO, CINAHL, ERIC, Web of Science and reference lists of included studies were searched in September 2018. Studies that quantitatively measured at least one of the main components of mental health literacy, including (a) knowledge of mental illnesses, (b) stigma towards mental illnesses, (c) confidence in helping students, and (d) behaviour of helping students, were included regardless of study design. Risk of bias was rated for each included study according to the Cochrane tool for randomized studies and the Cochrane tool, for raondomized studies, and the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS), for nonrandomized studies.

Results

Sixteen studies met the inclusion criteria, including 1 randomized controlled trial (RCT), 2 cluster RCTs, 1 controlled before‐and‐after study and 12 case series. Most of the studies claimed significant improvement of knowledge, attitudes, behaviour and/or confidence. However, the overall quality for all outcomes was relatively low; 15 studies had high/unclear risk of bias due to lack of allocation concealment, not controlling for confounders, and/or inadequate analysis for attrition.

Conclusions

More high quality evidence is required before the effectiveness of mental health literacy programs for teachers can be established.
Lifelong learning and the continued participation of older Norwegian adults in employment
Authors: Midtsundstad Tove , Nielsen Roy A.
Published: February 2019

The number of people aged 60 and over across the globe is expected to double by 2050, reaching a share of more than 20 percent of the population total. Governments are therefore taking more and more policy actions to encourage ageing workers to extend their working lives and their employers to retain them. According to the OECD lifelong learning opportunities and inclusive labour markets will be essential to ensuring that workers of all educational backgrounds have the possibility of extending their working lives. This article examines the relationship between adult education completed after age 40 and the subsequent active participation of older adults in employment, using individual register data from Statistics Norway.

The results show a substantial effect of upgrading formal education on subsequent labour market participation. Overall effects are quite similar for males and females. Attaining a lower level tertiary degree has the largest impact on labour market participation both for males and females. Completing a secondary education has a strong, long term impact among males. The results suggest that facilitating access to formal education among older workers may be an important contribution to extending working lives.
Cannabidiol in patients with Lennox‐Gastaut syndrome: Interim analysis of an open‐label extension study
Authors: Thiele Elizabeth , Marsh Eric , Mazurkiewicz‐Beldzinska Maria , Halford Jonathan J. , Gunning Boudewijn , Devinsky Orrin , Checketts Daniel , Roberts Claire
Published: February 2019

Objective

Patients with Lennox‐Gastaut syndrome (LGS) who completed 1 of 2 randomized, double‐blind, placebo‐controlled trials of add‐on cannabidiol (CBD) (GWPCARE3, NCT02224560 or GWPCARE4, NCT02224690) were invited to enroll in an open‐label extension (OLE) study evaluating the long‐term safety and efficacy of CBD (GWPCARE5, NCT02224573). Herein we present an interim analysis of the safety, efficacy, and patient‐reported outcomes from this trial.

Methods

Patients received a pharmaceutical formulation of highly purified CBD oral solution (Epidiolex; 100 mg/mL), titrated from 2.5 to 20 mg/kg/d over a 2‐week titration period, in addition to their existing medications. Doses could be reduced if not tolerated or increased up to 30 mg/kg/d if thought to be of benefit.

Results

This interim analysis was based on a November 2016 data cut. Of 368 patients who completed treatment in GWPCARE3 and GWPCARE4, 366 (99.5%) enrolled in the OLE study (GWPCARE5). Median treatment duration was 38 weeks at a mean modal dose of 23 mg/kg/d. Most patients (92.1%) experienced adverse events (AEs), primarily of mild (32.5%) or moderate (43.4%) severity. The most common AEs were diarrhea (26.8%), somnolence (23.5%), and convulsion (21.3%). Thirty‐five patients (9.6%) discontinued treatment due to AEs. Liver transaminase elevations were reported in 37 patients (10.1%), of whom 29 were receiving concomitant valproic acid; 34 cases resolved spontaneously or with dose modification of CBD or concomitant medication. Median reduction from baseline in drop seizure frequency (quantified monthly over 12‐week periods) ranged from 48% to 60% through week 48. Median reduction in monthly total seizure frequency ranged from 48% to 57% across all 12‐week periods through week 48. Eighty‐eight percent of patients/caregivers reported an improvement in the patient's overall condition per the Subject/Caregiver Global Impression of Change scale.

Significance

In this study, long‐term add‐on CBD treatment had an acceptable safety profile in patients with LGS and led to sustained reductions in seizures.
A potential contribution of decreased galectin‐7 expression in stratified epithelia to the development of cutaneous and oesophageal manifestations in systemic sclerosis
Authors: Saigusa Ryosuke , Yamashita Takashi , Miura Shunsuke , Hirabayashi Megumi , Nakamura Kouki , Miyagawa Takuya , Fukui Yuki , Yoshizaki Ayumi , Sato Shinichi , Asano Yoshihide
Published: February 2019

Backgrounds

Stratified epithelia have caught much attention as potential contributors to the development of dermal and oesophageal fibrosis in systemic sclerosis (SSc). Galectin‐7 is a marker of all types of stratified epithelia, which is involved in the maintenance of epidermal homeostasis. So far, the role of galectin‐7 has not been studied in SSc.

Objectives

To investigate the potential contribution of galectin‐7 to the development of clinical manifestations in SSc.

Methods

Galectin‐7 expression was examined in skin samples and cultured keratinocytes by immunostaining and/or quantitative reverse transcription PCR. Serum galectin‐7 levels were determined by enzyme‐linked immunosorbent assay in 63 SSc and 20 healthy subjects.

Results

Galectin‐7 expression was markedly decreased in the epidermis of SSc lesional skin compared with that of healthy control skin. Serum galectin‐7 levels were significantly lower in SSc patients than in healthy controls and inversely correlated with skin score. In addition, SSc patients with diffuse pigmentation and those with oesophageal dysfunction had significantly decreased serum galectin‐7 levels as compared to those without each symptom. Importantly, endothelin‐1 stimulation suppressed galectin‐7 expression in normal human keratinocytes, and bosentan, a dual endothelin receptor antagonist, reversed circulating galectin‐7 levels and epidermal galectin‐7 expression in SSc patients.

Conclusions

Galectin‐7 downregulation in stratified epithelia, which is mediated at least partially by autocrine endothelin stimulation, may contribute to the development of cutaneous manifestations and oesophageal dysfunction in SSc patients.
The home hemodialysis patient experience: A qualitative assessment of modality use and discontinuation
Authors: Seshasai Rebecca Kurnik , Wong Tiffany , Glickman Joel D. , Shea Judy A. , Dember Laura M.
Published: February 2019

Introduction: Home hemodialysis (HHD) is an under‐utilized renal replacement modality in the United States in part because of high rates of discontinuation and transfer to in‐center hemodialysis. Understanding, from the perspective of patients, facilitators, and barriers to sustained use of HHD is important for increasing successful use of this modality.

Methods: We conducted 25 semistructured interviews with 15 current and 10 former adult patients treated with home hemodialysis (23 short daily HHD and 2 nocturnal HHD). Interview transcripts were audiotaped, transcribed verbatim, and thematically analyzed.

Findings: Five themes related to continuation or discontinuation of HHD emerged: (1) degree of independence (increased flexibility, burden of therapy), (2) availability of support (emotional and physical support and caregiver burden), (3) technical aspects (familiarity with machine), (4) home environment (ability to organize supplies, space in home), and (5) attitude and expectations (positive or negative outlook about performing HHD). For each theme, positive aspects facilitated continuation of HHD and negative aspects contributed to discontinuation of HHD.

Discussion: HHD can be burdensome to patients and family members, and some discontinuations may be preventable. Helping patients with scheduling and organization, improving communication about expectations and trouble‐shooting, supporting patients as well as family members, adapting the dialysis prescription to the patient's lifestyle when possible, and providing respite when needed may make HHD more sustainable for patients.
Is there a relationship between plantar foot sensation and static balance, physical performance, fear of falling, and quality of life in hemodialysis patients?
Authors: Erdoğanoğlu Yıldız , Yalçin Berna , Külah Eyyüp , Kaya Defne
Published: February 2019

Introduction: This study was conducted to investigate the relationship between plantar foot sensation and static balance, physical performance, fear of falling, and quality of life in hemodialysis patients.

Materials and Methods: The study involved 24 hemodialysis patients and 20 healthy volunteers. Light touch‐pressure sensation (Semmes Weinstein Monofilament test kit), two‐point discrimination sensation (esthesiometer) and vibration sensation (128 Hz diapason) were used to evaluate plantar foot sensation. Static balance was assessed by the one‐leg standing balance test, physical performance by the Timed Up and Go test, fear of falling with the Fall Efficacy Scale, and quality of life with the Ferrans and Powers Quality of Life Index Dialysis Version.

Findings: There was a significant difference in plantar foot sensation, static balance, and physical performance of the patients compared to the healthy controls (P < 0.05). There was a strong correlation between static balance and physical performance with foot sensation in the hemodialysis patients (P < 0.05). There was also a strong correlation between static balance, physical performance, and fear of falling in hemodialysis patients (P < 0.05). The correlation between static balance, physical performance, and quality of life in the hemodialysis patients was strong (P < 0.05).

Discussion: The most important result of this study is that light touch‐pressure sensation, vibration sensation, two‐point discrimination sensation, static balance, and physical performance, all of which involve the activity of cutaneous sensory receptors on the sole of the foot, are reduced in individuals who undergo hemodialysis. The findings of this study suggest potential rehabilitation strategies that could be applied to this patient group.
Synthesis of nanostructured ThO2 pellets
Authors: De Bona Emanuele , Walter Olaf , Störmer Heike , Wiss Thierry , Baldinozzi Gianguido , Cologna Marco , Popa Karin
Published: February 2019

We present here for the first time the production of 3‐ to 5‐nm–sized thoria nanopowders by decomposition of Th‐hydroxide under hot compressed water and their consolidation by high‐pressure spark plasma sintering into dense nanostructured ThO2 with grain size of 50 nm.
Proliferation dynamics of WSSV in crayfish, Procambarus clarkii, and the host responses at different temperatures
Authors: Jiang Nan , Pan Xiaoyi , Gu Zemao , Liu Wenzhi , Si Kaige , Zhou Yong , Zhou Yongze , Zhai Liwen , Fan Yuding , Zeng Lingbing
Published: February 2019

The replication profile of white spot syndrome virus (WSSV) in crayfish, Procambarus clarkii, at different water temperature was investigated in this study. The WSSV detections were negative at 15 ± 1°C, and the natural infection ratio increased at 19 ± 1°C (24.2% ± 2.25%), reached 100% at 25 ± 1°C and decreased at 30 ± 1°C (93.2% ± 3.37%). The WSSV genome copies number was much higher at 25 ± 1°C (≥5 × 106.45 ± 0.35/mg) than at 15 ± 1°C (≤5 × 101.13 ± 0.12/mg), 19 ± 1°C (≤5 × 102.74 ± 0.48/mg) and 32 ± 1°C (≤5 × 103.18 ± 0.27/mg). Meanwhile, the significant transcription signals of immediate early gene ie1 and late gene vp28 and a large number of virus particles were detected in epitheliums of stomach, gut and gill, hepatopancreas, heart and muscle cells at 25 ± 1°C by using in situ hybridization (ISH) and transmission electron microscopy. The experimental infection of P. clarkii with WSSV infection showed reduced mortality and lower virus copies number at 19 ± 1°C (23.51% ± 0.84%, ≤5 × 103.41 ± 0.11/mg) and 32 ± 1°C (38.42% ± 1.21%, ≤5 × 103.72 ± 0.13/mg) compared to 25 ± 1°C (100%, ≥5 × 104.99 ± 0.24/mg). The water temperature regulated the transcription of immune‐related genes (crustin2, prophenoloxidase (proPO) and heat shock protein70 (Hsp70)), with some differences between WSSV treatments and control treatments. These results demonstrate that water temperature has effect on WSSV proliferation, which may due to transcriptional response of immune‐related genes to temperature.
Quorum sensing is required for full virulence of Vibrio campbellii towards tiger grouper (Epinephelus fuscoguttatus) larvae
Authors: Noor Noorashikin Md. , Defoirdt Tom , Alipiah Norfarrah , Karim Murni , Daud Hassan , Natrah Ikhsan
Published: February 2019

The link between quorum sensing in Vibrio campbellii and its virulence towards tiger grouper (Epinephelus fuscoguttatus) was investigated using V. campbellii wild type and quorum‐sensing mutants with inactive quorum sensing or constitutively maximal quorum‐sensing activity, and signal molecule synthase mutants. The results showed that wild‐type V. campbellii is pathogenic to grouper larvae, causing more than 50% mortality after 4 days of challenge. Furthermore, the mortality of larvae challenged with the mutant with maximally active quorum sensing was significantly higher than that of larvae challenged with the wild type, whereas a higher survival was observed in the larvae challenged to the mutant with a completely inactive quorum‐sensing system. Grouper larvae challenged with either the signal molecule synthase triple mutant, the harveyi autoinducer‐1 (HAI‐1) synthase mutant and the autoinducer‐2 (AI‐2) synthase mutant showed higher survival than larvae challenged with the wild type. In contrast, larvae challenged with the cholerae autoinducer‐1 (CAI‐1) synthase mutant showed high mortality. This indicates that HAI‐1 and AI‐2, but not CAI‐1, are required for full virulence of V. campbellii towards grouper larvae. Our data suggest that quorum‐sensing inhibition could be an effective strategy to control V. campbellii infections in tiger grouper.
Microstructure and compositional changes across biotite‐rich reaction selvedges around mafic schollen in a semipelitic diatexite migmatite
Authors: Lin Lina , Sawyer Edward W.
Published: February 2019

Biotite‐rich selvedges developed between mafic schollen and semipelitic diatexite in migmatites at Lac Kénogami in the Grenville Province of Quebec. Mineral equilibria modelling indicates that partial melting occurred in the mid‐crust (4.8–5.8 kbar) in the range 820–850°C. The field relations, petrography, mineral chemistry and whole‐rock composition of selvedges along with their adjacent mafic schollen and host migmatites are documented for the first time. The selvedges measured in the field are relatively uniform in width (~1 cm wide) irrespective of the shape or size of their mafic scholle. In thin section, the petrographic boundary between mafic scholle and selvedge is defined by the appearance of biotite and the boundary between selvedge and diatexite by the change in microstructure for biotite, garnet, plagioclase and quartz. Three subtypes of selvedges are identified according to mineral assemblage and microstructure. Subtype I have orthopyroxene but of different microstructure and Mg# to orthopyroxene in the mafic scholle; subtype II contain garnet with many mineral inclusions, especially of ilmenite, in contrast to garnet in the diatexite host which has few inclusions; subtype III lack orthopyroxene or garnet, but has abundant apatite. Profiles showing the change in plagioclase composition from the mafic schollen across the selvedge and into the diatexite show that each subtype of selvedge has a characteristic pattern.

Four types of biotite are identified in the selvedges and host diatexite based on their microstructural characteristics. (a) Residual biotite forms small rounded red‐brown grains, mostly as inclusions in peritectic cordierite and garnet in diatexite; (b) selvedge biotite forms tabular subhedral grains with high respect ratio; (c) diatexite biotite forms tabular subhedral grains common in the matrix of the diatexite; and (d) retrograde biotite that partially replaces peritectic cordierite and garnet in the diatexite. The four groups of biotite are also discriminated by their major element (EMPA) and trace elements (LA‐Q‐ICP‐MS) compositions. Residual biotite is high in TiO2 and low in Sc and S, whereas retrograde biotite has high Al2O3, but low Sc and Cr. Selvedge and diatexite biotite are generally very similar, but selvedge biotite has higher Sc and S contents. Whole‐rock compositional profiles across the selvedges constructed from micro‐XRF and LA‐Q‐ICP‐MS analyses show: (a) Al2O3, FeO, MgO and CaO all decrease from mafic scholle across the selvedge and into the diatexite; (b) Na2O is lowest in the mafic scholle, rises through the selvedge and reaches its maximum about 20–30 mm into the diatexite host; (c) K2O is lowest in the mafic scholle and reaches its highest value in the first half of the selvedge, then declines before reaching a higher, but intermediate value, about 20 mm into the diatexite. Of the trace elements, Cs and Rb show distributions very similar to K2O.
A brief history of circannual time
Authors: Lincoln Gerald
Published: February 2019

Innate circannual timing is an ancestral trait that first evolved in free‐living eukaryotic cells some 2000 million years ago, with marine algae of the genus Allexandrium providing a living unicellular model. This species shows the primitive trait of ‘alternation of generations’, where the organism alternates between fast replicating vegetative cells in the summer and a dormant cystic cell over the winter. The resistant cysts sink into the cold ocean sediments. Remarkably, excystment in spring is governed by an endogenous circannual timing mechanism. Thus, a tiny, short‐lived unicell can utilise a circannual clock as part of the life‐history programme of the species. Innate timing allows for major adjustments in physiology and behaviour in anticipation of the seasons, and provides an internalised sense of seasonal time for the many species where standard environmental cues are weak or ambiguous. This is a highly adaptive strategy irrespective of the size and longevity of an organism. Circannual rhythms are expressed by a diverse range of organisms, from flowering plants to mammals, interwoven into the life‐history programme of each species, being a consequence of forever living in a periodic world. In complex vertebrates, the early division of the zygote potentially carries circannual timer genes into all progeny cells and tissues. This supports the concept of a ‘clock‐shop’ where cell‐autonomous long‐term rhythms are generated in each tissue, orchestrated by a central circannual pacemaker system. This is analogous to the organisation of the circadian timing system. For the circannual time‐scale, specialised thyrotroph cells located in the pars tuberalis of the pituitary gland and adjacent tanycyte cells located in the ependymal wall of the third cerebral ventricle of the brain act as putative central circannual pacemakers. At a molecular level, epigenetically regulated, cyclical remodelling of chromatin, which determines whether specific circannual timer genes are transcriptionally active, or not, is considered to drive the oscillation between the summer and winter phenotypes.
Exploring the structure of narcissism: Toward an integrated solution
Authors: Crowe Michael L. , Lynam Donald R. , Campbell W. Keith , Miller Joshua D.
Published: February 2019

Objective

Despite decades of work on narcissism, there remain many active areas of exploration and debate including a clear and consensual description of its underlying components. Understanding narcissism's factor structure is necessary for the precise measurement and investigation of specific psychological and behavioral processes. The aim of the current study was to explore the structure of narcissism by examining it at varying hierarchical levels.

Method

Participants recruited from Amazon's Mechanical Turk (N = 591) completed 303 narcissism items encompassing 46 narcissism scales and subscales. Criterion variables measuring the five‐factor model, self‐esteem, aggression, and externalizing behavior were also collected.

Results

A series of factor analyses reveal the factor structure of narcissism at a range of specificities. No more than five meaningful factors (i.e., Grandiosity, Neuroticism, Antagonism, Distrustful Self‐reliance, Attention‐seeking) were identified and the most parsimonious model appears to be a three‐factor structure. Narcissism scales that effectively capture each of the identified factors are identified. Factors diverged in their associations with criterion variables.

Conclusions

A three‐factor model (i.e., Agentic Extraversion, Narcissistic Neuroticism, Self‐centered Antagonism) seems to be the most parsimonious conceptualization. Larger factor solutions are discussed, but future research will be necessary to determine the value of these increasingly narrow factors.
Relationship between endogenous melatonin concentrations and uterine contractions in late third trimester of human pregnancy
Authors: Rahman Shadab A. , Bibbo Carolina , Olcese James , Czeisler Charles A. , Robinson Julian N. , Klerman Elizabeth B.
Published: February 2019

In humans, circulating levels of the hormone melatonin and the initiation of spontaneous labor are both higher at night than during the day. Since activation of uterine melatonin receptors can stimulate human in vitro uterine contractions and these receptors are only expressed on the uterine tissue of women in labor, we hypothesized that circulating melatonin concentrations would affect uterine contractions in vivo. We evaluated the impact of light‐induced modulation of melatonin secretion on uterine contractions in women during late third trimester (~36‐39 weeks) of pregnancy in two inpatient protocols. We found a significant (P < 0.05) positive linear association between circulating melatonin concentrations and the number of uterine contractions under both protocols. On average, uterine contractions increased between 1.4 and 2.1 contractions per 30 minutes for every 10 pg/mL*h increase in melatonin concentration. These findings have both basic science and clinical implications for pregnant women, since endogenous melatonin levels and melatonin receptor activity can be altered by light and/or pharmaceutical agents.
Anthropometrical phenotypes are important when explaining obstructive sleep apnea in female bariatric cohorts
Authors: Gasa Mercè , López‐Padrós Carla , Monasterio Carmen , Salord Neus , Mayos Mercedes , Vilarrasa Núria , Fernandez‐Aranda Fernando , Montserrat Josep M. , Dorca Jordi
Published: February 2019

Central obesity is the main risk factor for obstructive sleep apnea (OSA). Whether there exists a central‐obesity anthropometric that better explains apnea–hypopnea index (AHI) variability in the general population and in sleep cohorts is unknown, and this is even less explored among increasing grades of obesity. The objective of the study is to investigate whether there is an anthropometric that better explains AHI variability in a sample of morbidly obese women awaiting bariatric surgery (BS). A prospective multicentre cross‐sectional study was conducted in consecutive women before BS. Demographic and anthropometric characteristics included age, body mass index (BMI), neck circumference (NC), waist circumference (WC), hip circumference (HC) and waist‐to‐hip ratio (WHR). OSA was diagnosed by polysomnography. The capacity of anthropometrics to explain AHI variance was investigated using regression linear models. A total of 115 women were evaluated: age, 44 ± 10 years; BMI, 46 ± 5 kg/m2; AHI, 35 ± 26 events/hr. AHI was associated with all anthropometrics except weight, height and HC. The best univariate predictor was WHR, which accounted for 15% of AHI variance. The simplest model (age + BMI) accounted for 9%, which increased to 20% when applying more complex measurements (age + BMI + NC + WC + HC). The explanatory capacity did not change significantly when applying a simpler model (age + WHR + NC, 19%). In this female morbidly obese cohort, anthropometrics explained one‐fifth of AHI variability. WHR is the best univariate parameter and models including waist and neck data provide more information than BMI when explaining AHI variability. Thus, even in young women with extreme obesity, OSA seems to be linked to a specific central‐obesity phenotype rather than to a whole‐obesity pattern.
Social ontology, practical reasonableness, and collective reasons for action
Authors: Ikuenobe Polycarp
Published: February 2019

I argue that the ontology of human social institutions and collective intentionality could be anchored in the normative notion of ‘practical reasonableness’ as collective reason for action. This involves the deontic idea of mutuality, accepted rules, and shared attitudes of other‐regardedness. I examine John Searle's three primitive notions of social ontology: collective intentionality, assignment of social functions, and constitutive rules and procedures. I use these notions to provide a plausible basis for understanding how people reason, in order to arrive at practically reasonable decisions and collective agency. Searle argues that social reality, institutions, processes, and facts are grounded in collective intentionality and the acceptance of social rules, procedures, and functions. I argue that collective intentionality and socially accepted rules are anchored in the need for human interdependence that engenders the social rules and norms or attitudes of ‘practical reasonableness’. I analyze the concept of ‘practical reasonableness’ as a representation of human mode of reasoning that involves collective intentionality.
Age‐stratified anti‐HAV positivity in Pune, India after two decades: Has voluntary vaccination impacted overall exposure to HAV?
Authors: Arankalle Vidya , Tiraki Divya , Kulkarni Ruta , Palkar Sonali , Malshe Nandini , Lalwani Sanjay , Mishra Akhilesh
Published: February 2019

The degree of transmission of hepatitis A virus (HAV) is inversely proportional to the socioeconomic status of a community. Serosurveys conducted at Pune, India during 1982‐98 documented significant reduction in HAV exposure of paediatric, higher socioeconomic status (HSS) population. Anti‐HAV positivity (ELISA) in age‐stratified Pune population representing HSS and lower middle socioeconomic status (LMSS) (n = 1065) and infants till the age of 15 months (n = 690) was determined in 2017. Anti‐HAV positivity in the LMSS population decreased significantly in 2017 while an increase was seen in the HSS category. The surprising rise in anti‐HAV positivity in the HSS population reflected vaccine‐ and infection‐induced antibodies while only infection‐induced antibodies were present in the LMSS category. Lowest antibody prevalence in infants was at 12 months, the recommended age for hepatitis A vaccination. Improved hygiene and selective immunization practices impacted HAV exposure of the LMSS population. The data emphasize the need for hepatitis A vaccination irrespective of socioeconomic status.
Low recurrence rate of hepatocellular carcinoma following ledipasvir and sofosbuvir treatment in a real‐world chronic hepatitis C patients cohort
Authors: Idilman Ramazan , Demir Mehmet , Aladag Murat , Erol Cihan , Cavus Bilger , Iliaz Raim , Koklu Hayrettin , Cakaloglu Yilmaz , Sahin Memduh , Ersoz Galip , Koksal İftihar , Karasu Zeki , Ozgenel Meric , Turan İlker , Gunduz Feyza , Ataseven Huseyin , Akdogan Meral , Kiyici Murat , Koksal Aydın Seref , Akhan Sila , Gunsar Fulya , Tabak Fehmi , Kaymakoglu Sabahattin , Akarca Ulus S ,   Early Access Program (EAP) Study Group
Published: February 2019

The aims of the present study were to evaluate the efficacy and tolerability of ledipasvir/sofosbuvir (LDV/SOF) with or without ribavirin in the treatment of chronic hepatitis C (CHC) in patients with advanced liver disease and to analyse whether the use of LDV/SOF treatment is associated with a new occurrence of hepatocellular carcinoma (HCC) during and after LDV/SOF treatment. The Turkish Early Access Program provided LDV/SOF treatment to a total of 200 eligible CHC patients with advanced liver disease. The median follow‐up period was 22 months. All patients were Caucasian, 84% were infected with genotype 1b, and 24% had a liver transplantation before treatment. The sustained virological response (SVR12) was 86.0% with ITT analysis. SVR12 was similar among patients with Child‐Pugh classes A, B and C disease and transplant recipients. From baseline to SVR12, serum ALT level and MELD score were significantly improved (P < 0.001). LDV/SOF treatment was generally well tolerated. Only one patient developed a new diagnosed HCC. Seventeen of the 35 patients, who had a history of previous HCC, developed HCC recurrence during the LDV/SOF treatment or by a median follow‐up of 6 months after treatment. HCC recurrence was less commonly observed in patients who received curative treatment for HCC compared with those patients who received noncurative treatment (P = 0.007). In conclusion, LDV/SOF with or without ribavirin is an effective and tolerable treatment in CHC patients with advanced liver disease. Eradication is associated with improvements in liver function and a reduced risk of developing a new occurrence of HCC.