bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of CYP1A2 genetic polymorphisms on pharmacokinetics of antipsychotic drugs: a systematic review and meta‐analysis
Authors: Na Takuathung M. , Hanprasertpong N. , Teekachunhatean S. , Koonrungsesomboon N.
Published: August 2018

Objective

To determine the impact of CYP1A2 genetic polymorphisms on the pharmacokinetics of CYP1A2‐metabolized antipsychotic drugs in humans by means of systematic review and meta‐analysis.

Method

A systematic search was conducted in PubMed and Scopus databases as of June 26, 2018. Studies reporting the pharmacokinetic parameters of CYP1A2‐metabolized antipsychotic drugs in individuals who were genotyped for CYP1A2 genetic polymorphisms were retrieved. Pharmacokinetic parameters of individuals who have mutant alleles of a CYP1A2 genetic polymorphism were compared with the wild‐type individuals. Pooled‐effect estimates, presented as standardized mean difference, were calculated by means of the fixed‐effect or random‐effects model, as appropriate.

Results

Ten studies involving 872 clozapine users, seven studies involving 712 olanzapine users, and two studies involving 141 haloperidol users were included. All but one study reported no associations between any CYP1A2 genetic polymorphisms and the pharmacokinetics of CYP1A2‐metabolized antipsychotic drugs. The pooled‐effect estimates through meta‐analyses of seven studies demonstrated no significant associations between the ‐163C>A or ‐2467delT polymorphism and clozapine or olanzapine concentrations in the blood.

Conclusions

This study suggests that CYP1A2 genetic polymorphisms have no significant impact on the pharmacokinetics of CYP1A2‐metabolized antipsychotic drugs. CYP1A2 genotyping may have no clinical implications for personalized dosing of CYP1A2‐metabolized antipsychotic drugs.
Computed microtomography study of untreated, shaped and filled mesiobuccal canals of maxillary first molars
Authors: Angerame Daniele , De Biasi Matteo , Brun Francesco , Turco Gianluca , Franco Vittorio
Published: August 2018

This study assessed the effectiveness of modern endodontic shaping and filling procedures on mesiobuccal roots of maxillary molars with two canals. The canals of 20 mesiobuccal roots were treated with Mtwo rotary files, passive ultrasonic irrigation and Guttafusion obturators. X‐ray computed microtomography analysis was carried out prior to treatment, after canal shaping and after canal filling to determine the alterations of the canal volume before and after the instrumentation, the volume of the hard tissue debris, and percentage of the volume occupied by filling materials. The shaping instruments and filling materials reached only partially the endodontic space of the second mesiobuccal canal and the accessory endodontic structures. Canal irregularities, ramifications, and interconnections were accumulation sites of hard tissue debris. This study demonstrated that rotary files, passive ultrasonic irrigation and carrier‐based filling systems could be partially effective for the treatment of the mesiobuccal canals and their accessory endodontic structures.
Antimicrobial efficacy of clindamycin and triple antibiotic paste as root canal medicaments on tubular infection: An in vitro study
Authors: Zargar Nazanin , Rayat Hosein Abadi Motahare , Sabeti Mohammad , Yadegari Zahra , Akbarzadeh Baghban Alireza , Dianat Omid
Published: August 2018

This study compared the antibacterial effect of 2% clindamycin and 2% and 100% concentration of triple antibiotic paste (TAP) on an Enterococcus faecalis biofilm. Dentinal tubules of 100 root specimens were infected and randomly assigned to five groups. A total of 1000 mg mL−1 of TAP, 20 mg mL−1 of TAP and clindamycin, calcium hydroxide or methylcellulose (control) were placed in the root canal for 1 week. After treatment, dentine shavings were collected from 200 and 400 μm dentine depth and the number of colony‐forming units (CFU) per mg was determined. Reduction in viable bacteria in first three groups was significantly better than calcium hydroxide and control groups. However, the antimicrobial effectiveness among these three groups was not significantly different from each other. There was no significant difference between data at 200 and 400 μm in all groups except the Ca(OH)2 group. The antibiofilm effect of clindamycin was comparable with TAP, so it may be used instead of TAP.
Effectiveness of calcium and sodium hypochlorite in association with reciprocating instrumentation on decontamination of root canals infected with Enterococcus faecalis
Authors: Dal Bello Yuri , Mezzalira Gean I. , Jaguszewski Luis A. , Hoffmann Igor P. , Menchik Vitor Hugo S. , Cecchin Doglas , Souza Matheus A.
Published: August 2018

The aim of this study was to evaluate the antimicrobial activity of sodium and calcium hypochlorite utilising reciprocating instrumentation. Sixty root canals were inoculated with E. faecalis for 14 days. Samples were divided into six groups according to decontamination protocol: G1: no treatment, G2: distilled water, G3: 2.5% sodium hypochlorite, G4: 2.5% calcium hypochlorite, G5: 5.25% sodium hypochlorite and G6: 5.25% calcium hypochlorite. Instrumentation was performed with Wave One reciprocating system (Dentsply Sirona Endodontics, York, PA, USA) in groups G2 to G6. Colony‐forming units (CFUs) counting was performed and the data were subjected to Anova and Tukey (α  =  0.05). Group 1 and 2 showed the highest mean contamination, with a significant difference between them (P < 0.05). Groups 3, 4, 5 and 6 showed the lowest contamination means with no significant difference between them (P < 0.05). Sodium and calcium hypochlorite, in association with reciprocating instrumentation, can be an effective decontamination protocol in root canals infected with E. faecalis.
Endodontic treatment of a hypertaurodontic mandibular left second molar in a patient with many taurodonts combined with multiple pulp stones
Authors: Lim Adrian , Le Clerc Justine
Published: August 2018

Taurodontism is a rare embryologic anomaly of teeth, defined by an apical displacement of the furcation of roots and enlarged pulp chambers. Taurodontism has been classified as hypo‐, meso‐ or hypertaurodontism according to the severity of the anomaly. The aim of this case report was to illustrate a clinical case with multiple bilateral taurodonts and to describe the endodontic management of the hypertaurodontic mandibular left second molar with a C‐shaped canal and extensive dental pulp calcifications. A healthy 20‐year‐old male patient was referred for the endodontic treatment of his lower left second molar. Cone beam computed tomography revealed a C‐shaped root canal configuration and several dental pulp calcifications in this tooth. The endodontic treatment was performed in two appointments under an operating dental microscope. A panoramic radiograph, made during the 18 months follow‐up appointment, revealed nine other taurodontic molars, most of them associated with dental pulp calcifications.
Classification and cyclic fatigue evaluation of new kinematics for endodontic instruments
Authors: Gambarini Gianluca , Piasecki Lucila , Miccoli Gabriele , Gaimari Gianfranco , Di Giorgio Roberto , Di Nardo Dario , Azim Adham A , Testarelli Luca
Published: August 2018

This study evaluated the effect of new motions of the motor TriAuto ZX2 on the cyclic fatigue of endodontic instruments. Vortex Blue 35.06 instruments were divided into four groups (n = 10) and tested for fatigue in a curved artificial canal (90° and 2 mm radius) using the following motions: continuous rotation (CR), Optimum Torque Reverse (OTR) set at 180° and the Optimum Glide Path (OGP), which was tested at 90° and 240°. The time to fracture (TTF) and the lengths of the fractured fragments were recorded. The mean TTF was significantly different among the groups (anova, P < 0.05): OGP 90° (213.39 ± 27.45), OTR 180° (121.24 ± 17.03), OGP 240° (45.24 ± 5.61) and CR (8.43 ± 1.27). Weibull analysis confirmed the shortest life expectancy for CR and the longest survival for OGP at 90°. The resistance to fatigue was affected by motions and pre‐set angles. The proprietary movements that are currently available for endodontic instruments were classified according to their kinematics.
Paediatric intensive care and neonatal intensive care airway management in the United Kingdom: the PIC‐NIC survey
Authors: Foy K. E. , Mew E. , Cook T. M. , Bower J. , Knight P. , Dean S. , Herneman K. , Marden B. , Kelly F. E.
Published: August 2018

In 2011, the Fourth National Audit Project (NAP4) reported high rates of airway complications in adult intensive care units (ICUs), including death or brain injury, and recommended preparation for airway difficulty, immediately available difficult airway equipment and routine use of waveform capnography monitoring. More than 80% of UK adult intensive care units have subsequently changed practice. Undetected oesophageal intubation has recently been listed as a ‘Never Event’ in UK practice, with capnography mandated. We investigated whether the NAP4 recommendations have been embedded into paediatric and neonatal intensive care practice by conducting a telephone survey of senior medical or nursing staff in UK paediatric intensive care units (PICUs) and neonatal intensive care units (NICUs). Response rates were 100% for paediatric intensive care units and 90% for neonatal intensive care units. A difficult airway policy existed in 67% of paediatric intensive care units and in 40% of neonatal intensive care units; a pre‐intubation checklist was used in 70% of paediatric intensive care units and in 42% of neonatal intensive care units; a difficult intubation trolley was present in 96% of paediatric intensive care units and in 50% of neonatal intensive care units; a videolaryngoscope was available in 55% of paediatric intensive care units and in 29% of neonatal intensive care units; capnography was ‘available’ in 100% of paediatric intensive care units and in 46% of neonatal intensive care units, and ‘always available’ in 100% of paediatric intensive care units and in 18% of neonatal intensive care units. Death or serious harm occurring secondary to complications of airway management in the last 5 years was reported in 19% of paediatric intensive care units and in 26% of neonatal intensive care units. We conclude that major gaps in optimal airway management provision exist in UK paediatric intensive care units and especially in UK neonatal intensive care units. Wider implementation of waveform capnography is necessary to ensure compliance with the new ‘Never Event’ and has the potential to improve airway management.
Comparison of injectate spread and nerve involvement between retrolaminar and erector spinae plane blocks in the thoracic region: a cadaveric study
Authors: Yang H.‐M. , Choi Y. J. , Kwon H.‐J. , O J. , Cho T. H. , Kim S. H.
Published: August 2018

Although different injection locations for retrolaminar and erector spinae plane blocks have been described, the two procedures have a similar anatomical basis. In this cadaveric study we compared anatomical spread of dye in the thoracic region following these two procedures. Following randomisation, 10 retrolaminar blocks and 10 erector spinae plane blocks were performed on the left or right sides of 10 unembalmed cadavers. For each block, 20 ml of dye solution was injected at the T5 level. The back regions were dissected and the involvement of the thoracic spinal nerve was also investigated. Twenty blocks were successfully completed. A consistent vertical spread, with deep staining between the posterior surface of the vertebral laminae and the overlaying transversospinalis muscle was observed in all retrolaminar blocks. Moreover, most retrolaminar blocks were predominantly associated with fascial spreading in the intrinsic back muscles. With an erector spinae plane block, dye spread in a more lateral pattern than with retrolaminar block, and fascial spreading in the back muscles was also observed. The number of stained thoracic spinal nerves was greater with erector spinae plane blocks than with retrolaminar blocks; median 2.0 and 3.5, respectively. Regardless of technique, the main route of dye spread was through the superior costotransverse ligament to the ipsilateral paravertebral space. Although erector spinae plane blocks were associated with a slightly larger number of stained thoracic spinal nerves than retrolaminar blocks, both techniques were consistently associated with posterior spread of dye and with limited spread to the paravertebral space.
A systematic review of clinicians' views and experiences of direct‐acting oral anticoagulants in the management of nonvalvular atrial fibrillation
Authors: Generalova Daria , Cunningham Scott , Leslie Stephen J. , Rushworth Gordon F. , McIver Laura , Stewart Derek
Published: August 2018

Aims

While a plethora of systematic reviews have provided evidence of efficacy, effectiveness and safety of direct‐acting oral anticoagulants (DOACs) in the management of nonvalvular atrial fibrillation, there has been little emphasis on clinicians' perspectives. This systematic review aimed to critically appraise, synthesize and present the available evidence of clinicians' views and experiences.

Methods

Studies published in English from January 2006 to July 2017 reporting the views and/or experiences of doctors, nurses or pharmacists on any individual DOAC or as a pharmacological group were included. Studies were assessed for quality by two researchers, data extracted and findings synthesized using a narrative approach.

Results

Following exclusion of duplicates, 777 titles, 394 abstracts and 196 studies were screened. Ten studies were included in the review, nine of which were quantitative (cross‐sectional surveys) and one qualitative (semistructured interviews), with marked heterogeneity in outcomes reported. Studies were conducted exclusively in Europe and the USA. In those studies reporting clinician preference, DOACs were first choice over warfarin in naïve patients, based on perceptions of evidence of effectiveness equivalent or superior to warfarin and superior safety. Other advantageous factors were in those with an unstable International Normalized Ratio and likely to miss appointments. There were, however, concerns relating to management of over‐anticoagulation and experiences of observed bleeding rates.

Conclusion

There is a limited evidence base of clinicians' perspectives of DOACs, necessitating further research, particularly given the trajectory of increased use worldwide.
Interaction of the originality of peers’ ideas and students’ openness to experience in predicting creativity in online collaborative groups
Authors: Pi Zhongling , Hong Jianzhong , Hu Weiping
Published: August 2018

There has been growing interest in the possibility that peers’ ideas can stimulate students’ creativity in group contexts. However, empirical research on this issue is limited. This study tested the hypothesis that peers’ ideas and students’ openness to experience would predict student creativity and attention to peers’ ideas. Undergraduate students (n = 60) completed creative tasks in an online collaborative group in which the ideas of “peers” were pre‐programmed. Mixed ANOVAs showed support for the hypothesis. Specifically, students with higher (but not lower) openness, when exposed to a high (but not low) rate of peers’ original ideas, paid greater attention to those ideas and were more creative. The implication for education is that teachers should encourage students to share more of their original ideas and to pay more attention to peers’ ideas in online collaborative groups.
Optimization of the 2014 Gleason grade grouping in a Canadian cohort of patients with localized prostate cancer
Authors: Wissing Michel , Brimo Fadi , Chevalier Simone , Scarlata Eleonora , McKercher Ginette , O'Flaherty Ana , Aprikian Saro , Thibodeau Valérie , Saad Fred , Carmel Michel , Lacombe Louis , Têtu Bernard , Ekindi‐Ndongo Nadia , Latour Mathieu , Trudel Dominique , Aprikian Armen
Published: August 2018

Objectives

To evaluate the five‐tier Gleason grade group (GG) scoring of prostate cancers adopted by the International Society of Urology Pathology (ISUP) in 2014, and to propose modifications to optimize its performance.

Patients and Methods

Data were obtained from PROCURE, a prospective cohort of patients with localized prostate cancer undergoing radical prostatectomy in Québec, 2006–2013. Surgical specimens were evaluated by genitourinary pathologists using 2014 ISUP criteria. Treatment failure was defined as biochemical recurrence and/or initiation of secondary, non‐adjuvant therapy. Analyses were conducted using Kaplan–Meier methods, log‐rank tests, Cox proportional hazards models and Harrell's concordance indices.

Results

A total of 1 917 patients were included, with a median follow‐up of 69 months. The 5‐year treatment failure rates were 9.6%, 23.5%, 43.1%, 52.6% and 84.3% in GG1–5, respectively (P < 0.001 when comparing GG2 with GG3). Treatment failure rates for patients in GG2 and GG3 with tertiary Gleason 5 pattern were higher than patients in the same group without a tertiary pattern (P < 0.001), but were similar to rates for patients in GGs 3 or 4 without a tertiary pattern (P > 0.3). Primary Gleason pattern (4/5) predicted treatment failure in GG5 (5‐year failure rates 82.3% vs 97.1%, respectively; P = 0.001). The five‐tier GG system had greater accuracy as a prognostic indicator compared with the four‐tier system (Harrell's concordance index 0.716 vs 0.676). When upgrading patients in GG2/3 with tertiary Gleason 5 pattern to patients in GG3/4, and separating patients in GG5 by primary Gleason pattern, the Harrell's concordance index increased to 0.730.

Conclusion

The five‐tier GG system increased accuracy for predicting treatment failure compared with the previous grading systems, but can be further improved.
Bladder emptying method is the primary determinant of urinary tract infections in patients with spinal cord injury: results from a prospective rehabilitation cohort study
Authors: Anderson Collene E. , Chamberlain Jonviea D. , Jordan Xavier , Kessler Thomas M. , Luca Eugenia , Möhr Sandra , Pannek Jürgen , Schubert Martin , Brinkhof Martin W. G. ,   the SwiSCI Study Group
Published: August 2018

Objective

To understand the occurrence of and risk factors for urinary tract infections (UTIs) in patients with spinal cord injury (SCI) undergoing specialized SCI rehabilitation in Switzerland.

Patients and Methods

This study used data collected from 369 patients, who participated in a nationwide rehabilitation cohort for SCI in Switzerland between 2013 and 2017. Information on UTIs as well as their potential determinants, including demographics, lesion characteristics, and time‐updated data on functional independence and bladder management, was used. Multivariable regression methods were applied to perform a time‐updated evaluation of determinants of UTI risk.

Results

The crude incidence rate (IR) of UTIs was 0.55 UTIs per 100 person‐days (95% confidence interval [CI] 0.49–0.62), the cumulative IR was 43%, and the median length of stay was 122 days. The bladder emptying method at discharge was largely determined by 28 days after admission. Among those using indwelling or assisted intermittent catheterization (IC), the likelihood of self‐IC at discharge was positively related to the level of self‐care independence, negatively related to age at injury, and lower in women than men. Catheter users consistently had higher adjusted IRs for UTI than spontaneous voiders. The IR ratios were: indwelling catheter: 5.97 (95% CI 2.63–13.57); assisted IC: 6.05 (95% CI 2.63–13.94); self‐IC: 5.16 (95% CI 2.31–11.52); test for differences across catheter groups: P = 0.82. Lesion severity and previous UTI had additional but smaller effect sizes.

Conclusions

Bladder emptying method was identified as the main risk factor for UTI in patients with SCI. As spontaneous voiders had the lowest UTI rate, further research is warranted to reduce voiding dysfunction, for instance using neuromodulation procedures.
Current management of radiation cystitis: a review and practical guide to clinical management
Authors: Pascoe Claire , Duncan Catriona , Lamb Benjamin W. , Davis Niall F. , Lynch Thomas H. , Murphy Declan G. , Lawrentschuk Nathan
Published: August 2018

Introduction

Haemorrhage is a frequent complication of radiation cystitis leading to emergency presentations in patients with prior pelvic radiation therapy. Standard initial patient management strategies involve resuscitation, bladder washout with clot evacuation and continuous bladder irrigation. Beyond this, definitive surgical treatment is associated with significant morbidity and mortality. Alternative less invasive management options for non‐emergent haemorrhagic cystitis include systemic medical therapies, hyperbaric oxygen (HBO), intravesical therapies and laser ablation. However, evidence to support and compare treatment for haemorrhagic radiation cystitis is limited.

Methods

Herein, a literature search pertaining to the current management of haemorrhagic cystitis was conducted.

Results

In total, 23 studies were included in this review with 2 studies reviewing systemic therapy, 7 studies evaluating HBO therapy, 10 studies investigating a variety of intravesical therapies and the remaining 4 were relating to ablative therapies. Across these studies, the patient groups were heterogenous with small numbers and variable follow up periods.

Conclusion

With evaluation of existing literature, this narrative review also provides a stepwise clinical algorithm to aid the urologist in treating patients presenting with complications associated with radiation cystitis.
An analysis of the frequency of Y‐chromosome microdeletions and the determination of a threshold sperm concentration for genetic testing in infertile men
Authors: Johnson Mark , Raheem Amr , De Luca Francesco , Hallerstrom Marcus , Zainal Yasmeen , Poselay Sameer , Mohammadi Baharak , Moubasher Amr , Johnson Thomas Frederick , Muneer Asif , Sangster Philippa , Ralph David J.
Published: August 2018

Objective

To describe the prevalence of Y‐chromosome microdeletions in a multi‐ethnic urban population in London, UK. To also determine predictive factors and a clinical threshold for genetic testing in men with Y chromosome microdeletions.

Patients and Methods

A retrospective cohort study of 1473 men that were referred to a tertiary Andrology centre with male factor infertility between July 2004 and December 2016. All had a genetic evaluation, hormonal profile and 2 abnormal semen analyses. Those with abnormal examination findings also had targeted imaging performed.

Results

The prevalence of microdeletions was 4% (n = 58) in this study. These microdeletions were partitioned into the following regions: Azoospermia factors (AZF); AZFc (75%), AZFb+c (13.8%), AZFb (6.9%), AZFa (1.7%), and partial AZFa (1.7%). A high follicle‐stimulating hormone level (P < 0.001) and a low sperm concentration (P < 0.05) were both found to be significant predictors for the identification of a microdeletion. Testosterone level, luteinising hormone level and testicular volume did not predict the presence of a microdeletion. None of the men with an AZF microdeletion had a sperm concentration of >0.5 million/mL. Lowering the sperm concentration threshold to this level retained the high sensitivity (100%) and increased the specificity (31%). This would produce significant cost savings when compared to the European Academy of Andrology/European Molecular Genetics Quality Network and European Association of Urology guidelines. The surgical sperm retrieval (SSR) rate after microdissection testicular sperm extraction was 33.2% in men with AZFc microdeletion.

Conclusions

The prevalence of Y‐chromosome microdeletions in infertile men appears to vary between populations and countries. A low sperm concentration was a predictive factor (P < 0.05) for identifying microdeletions in infertile males. A threshold for genetic testing of 0.5 million/mL would increase the specificity and lower the relative cost without adversely affecting the sensitivity. The rate of SSR was lower than that previously described in the literature.
Phenotypic severity scoring system and categorisation for prune belly syndrome: application to a pilot cohort of 50 living patients
Authors: Wong Daniel G. , Arevalo Michelle K. , Passoni Niccolo Maria , Iqbal Nida S. , Jascur Thomas , Kern Adam J. , Sanchez Emma J. , Satyanarayan Arthi , Gattineni Jyothsna , Baker Linda A.
Published: August 2018

Objective

To design a novel system of scoring prune belly syndrome (PBS) phenotypic severity at any presenting age and apply it to a large pilot cohort.

Patients and Methods

From 2000 to 2017, patients with PBS were recruited to our prospective PBS study and medical records were cross‐sectionally analysed, generating individualised RUBACE scores. We designed the pragmatic RUBACE‐scoring system based on six sub‐scores (R: renal, U: ureter, B: bladder/outlet, A: abdominal wall, C: cryptorchidism, E: extra‐genitourinary, generating the acronym RUBACE), yielding a potential summed score of 0–31. The ‘E’ score was used to segregate syndromic PBS and PBS‐plus variants. The cohort was scored per classic Woodard criteria and RUBACE scores compared to Woodard category.

Results

In all, 48 males and two females had a mean (range) RUBACE score of 13.8 (8–25) at a mean age of 7.3 years. Segregated by phenotypic categories, there were 39 isolated PBS (76%), six syndromic PBS (12%) and five PBS‐plus (10%) cases. The mean RUBACE scores for Woodard categories 1, 2, and 3 were 20.5 (eight patients), 13.8 (25), and 10.6 (17), respectively (P < 0.001).

Conclusions

RUBACE is a practical, organ/system level, phenotyping tool designed to grade PBS severity and categorise patients into isolated PBS, syndromic PBS, and PBS‐plus groups. This standardised system will facilitate genotype–phenotype correlations and future prospective multicentre studies assessing medical and surgical treatment outcomes.
FOXM1 overexpression is associated with adverse outcome and predicts response to intravesical instillation therapy in stage pT1 non‐muscle‐invasive bladder cancer
Authors: Breyer Johannes , Wirtz Ralph M. , Erben Philipp , Rinaldetti Sebastien , Worst Thomas S. , Stoehr Robert , Eckstein Markus , Sikic Danijel , Denzinger Stefan , Burger Maximilian , Hartmann Arndt , Otto Wolfgang
Published: August 2018

Objective

To investigate the role of forkhead box protein M1 (FOXM1) mRNA expression and its prognostic value in stage pT1 non‐muscle‐invasive bladder cancer (NMIBC).

Patients and Methods

Clinical data and formalin‐fixed paraffin‐embedded tissues from transurethral resection of the bladder from patients with stage pT1 NMIBC, treated with an organ‐preserving approach, were analysed retrospectively. Total RNA was isolated using commercial RNA extraction kits, and mRNA expression of FOXM1, MKI67, KRT20 and KRT5 was measured by single‐step quantitative RT‐PCR using RNA‐specific TaqMan Assays. Statistical analysis was performed using Spearman's Rho, Wilcoxon or Kruskal–Wallis tests, Kaplan–Meier estimates of recurrence‐free (RFS), progression‐free (PFS) and cancer‐specific survival (CSS) and Cox regression analysis.

Results

Data from 296 patients (79.4% men, median age 72 years) were available for the final evaluation. Spearman correlation analysis showed that mRNA expression of FOXM1 was significantly correlated with MKI67 (ρ: 0.6530, P < 0.001) and with the luminal subtype, reflected by the positive correlation with KRT20 (ρ: 0.2113, P < 0.001). Furthermore, there was also a strong correlation of FOXM1 expression with adverse clinical and pathological variables, such as concomitant carcinoma in situ (P = 0.05), multifocal tumours (P = 0.005) and World Health Organization 1973 grade 3 disease (P < 0.001). Kaplan–Meier analysis showed overexpression of FOMX1 to be associated with worse PFS (P = 0.028) and worse CSS (P = 0.015). FOXM1 overexpression was also shown to be a predictive risk factor for CSS (hazard ratio 1.61 [1.13–2.34], L‐R chi‐squared: 7.19, P = 0.007). FOXM1 overexpression identified a subgroup of patients within the luminal subtype with worse RFS (P = 0.017), PFS (P < 0.001) and CSS (P = 0.015). Patients with low FOXM1 expression had better outcomes, irrespective of instillation therapy, whereas patients with high FOXM1 expression benefitted from intravesical chemotherapy with mitomycin C.

Conclusion

High FOXM1 expression was associated with adverse clinical and pathological features and worse outcomes, and predicted response to intravesical instillation therapy in patients with stage pT1 NMIBC.
Quaternary interaction of cryospheric and oceanographic processes along the central‐east Greenland margin
Authors: Pérez Lara F. , Nielsen Tove , Rasmussen Tine L. , Winsborrow Monica
Published: August 2018

The east Greenland margin has been influenced by oceanographic and cryospheric processes since the late Miocene, when the southwards flow of the East Greenland Current (EGC) initiated and ice sheets first advanced across the margin. However, the relative importance of these processes, and their influence on the sedimentation of the margin through time remains poorly understood. High‐resolution single‐channel seismic, chirp sub‐bottom profiles and swath bathymetry data were acquired along the middle/lower slope and proximal basinal area off Liverpool Land, central‐east Greenland margin. In this study, seismic‐stratigraphical and morphological analyses allowed us to distinguish between the major sedimentary processes that influenced this margin during the Quaternary. The stratigraphical architecture reveals mass transport deposits (MTDs) related to glacially influenced down‐slope sedimentation. These are intercalated with buried contourite systems associated with bottom‐current controlled along‐slope sedimentation. The distribution of the MTDs suggests the influence of two distinct ice‐stream systems. Initial phases of down‐slope deposition during the early‐middle Quaternary appears to be related to distal deposition fed by an ice stream from the Scoresby Sund area in the south. Shallow sedimentary processes, together with morphological analysis of the sea floor, show that the most recent activity of down‐slope processes during the latest Quaternary has occurred in the north, linked to an ice stream from the Kong Oscar Fjord area. These observations document a temporal shift in the relative dominance of the Scoresby Sund and Kong Oscar Fjord ice‐stream systems. The glacial influence on the margin has been interrupted by periods of stronger activity of along‐slope bottom‐current flow, demonstrating that the EGC periodically controlled sedimentation on the continental margin.
Commentary: What aspects of good practice in early interventions in psychosis can be codified in guidelines? – A commentary on Corsico et al. (2018)
Authors: Jefferson Anneli , Bortolotti Lisa
Published: August 2018

Read the full article at doi:10.1111/camh.12229

Read the Response to this Commentary at doi:10.1111/camh.12292
PGK1 as an immune target in Kawasaki disease
Authors: Cui J , Zhou Y , Hu H , Zhao L , Du Z , Du H
Published: August 2018

Kawasaki disease (KD) is an immune-mediated vasculitis with symptoms that mimic febrile illness; the immune origin has been suggested but never proved. First, cell chip technology was used to screen immune targets cells. With the indirect immunofluorescence assay we found that the HeLa cell chip could be recognized by KD patient serum samples. The target cell proteome was extracted as antigens, and antigen recognition reaction was performed using the patients’ serum as antibodies and the detected target protein was detected and identified as phosphoglycerate kinase 1 (PGK1). Then PGK1 was produced and tested with enzyme-linked immunosorbent assay (ELISA), Western blotting, immunoprecipitation and competitive inhibition immunofluorescence assay. Immunoglobulin (Ig)G against PGK1 was detected in 46% (23 of 50) sera of KD patients, 13% (five of 38) sera in febrile non-KD patients (FC) and 2·6% (one of 38) sera in healthy donors. As an immune target, PGK1 not only helps understanding of the pathogenesis, it also has potential value in facilitating the laboratory diagnosis of KD.
Factors impacting on the action of glucocorticoids in patients receiving glucocorticoid therapy
Authors: Dineen Rosemary , Stewart Paul M. , Sherlock Mark
Published: August 2018

Glucocorticoids (GCs) are steroid hormones, which are essential for life. They are secreted by the adrenal cortex under the control of the hypothalamic‐pituitary‐adrenal (HPA) axis. Glucocorticoids are essential for the normal function of most organ systems and, in both, excess and deficiency can lead to significant adverse consequences. Adrenal insufficiency (AI) is a rare, life‐threatening disorder characterized by insufficient production of corticosteroid hormones. Primary AI is defined by the inability of the adrenal cortex to produce sufficient amounts of glucocorticoids and/or mineralocorticoids despite normal or increased adrenocorticotropin hormone (ACTH). Secondary AI is adrenal hypofunction due to insufficient amount of ACTH produced by the pituitary gland. Conventional treatment of both primary and secondary adrenal insufficiencies involves lifelong glucocorticoid replacement therapy. The role of cortisol deficiency and the impact of hydrocortisone replacement on morbidity and mortality in this patient group are under increasing scrutiny. Established glucocorticoid replacement regimens do not completely mirror endogenous hormonal production, and their monitoring to ensure optimum therapy is hampered by the lack of reliable biomarkers of hormone sufficiency. A further confounding issue is the tissue‐specific regulation of glucocorticoid through the two isozymes of 11β‐hydroxysteroid dehydrogenase (11β‐HSD) with research focusing on the role of this prereceptor regulation in the development of adverse metabolic features in patients. This review defines the factors influencing glucocorticoid action in patients with adrenal insufficiency receiving glucocorticoid therapy.
Improving decision‐making in care order proceedings: A multijurisdictional study of court decision‐makers' viewpoints
Authors: Skivenes Marit , Tonheim Milfrid
Published: August 2018

Child welfare removals of children are among the most invasive decisions a state can make toward its citizens, and typically it is the courts that make these decisions. These interventions are regularly exposed to criticism. In this paper, we examine if and how care order proceedings could be improved in England, Finland, Norway, and California, USA. We have asked the judiciary decision‐makers about their view on what should be improved. Our findings show that the organization of the proceedings, including time and staff, are identified as issues in all four systems. Furthermore, the preparations by the child welfare agency are also mentioned as an issue, for English, Finnish, and Californian decision‐makers. Very few decision‐makers indicate features related to the individual, situational, and contextual dimensions, which is interesting since this would be expected from organization theory. The strong call for change in the way proceedings are organized indicates a need for modernization as well as better use of available competency from child development experts. The respondents focus on the elements that a decision‐maker has direct experience with and knowledge about, and this is indeed worth noting for policymakers in the four systems.
The Micropolitics of Dispossession and Resistance: Case Study of a Proposed Dam in Central India
Authors: Kabra Asmita , Mahalwal Sonam
Published: August 2018

This article presents a study of the micropolitics of dispossession for a proposed medium‐sized irrigation project in an Adivasi region of Central India. The article explores the complex micropolitics of dispossession and collective action in the project planning stage, long before the formal processes of land acquisition actually begin. It highlights the importance of training the researchers’ gaze on the functioning of the local state in the pre‐acquisition phase. It shows how the local state uses various powers of exclusion to fracture emerging cross‐class, multi‐caste alliances, while maintaining formal compliance with a range of social safeguard policies aimed at protecting vulnerable groups and fragile landscapes. The ‘everyday’ decisions of local state actors during the project planning stage produce site‐specific, differentiated and shifting matrices of risks and opportunities for the local people, who are already divided along class and caste lines. This, in turn, is likely to inform their political responses at the actual moment of enclosure. Thus the durability and success of anti‐dispossession collective action is likely to vary depending on the dynamic interactions of local state and non‐state actors, mediated by regional electoral politics and the overall safeguard policy regime governing land acquisition.
Accounting for the shared environment in cognitive abilities and academic achievement with measured socioecological contexts
Authors: Engelhardt Laura E. , Church Jessica A. , Paige Harden K. , Tucker‐Drob Elliot M.
Published: August 2018

Behavioral and molecular genetic research has established that child cognitive ability and academic performance are substantially heritable, but genetic variation does not account for all of the stratification of cognitive and academic outcomes across families. Which specific contexts and experiences contribute to these shared environmental influences on cognitive ability and academic achievement? Using an ethnically and socioeconomically diverse sample of N = 1728 twins ages 7–20 from the Texas Twin Project, we identified specific measured family, school, and neighborhood socioecological contexts that statistically accounted for latent shared environmental variance in cognitive abilities and academic skills. Composite measures of parent socioeconomic status (SES), school demographic composition, and neighborhood SES accounted for moderate proportions of variation in IQ and achievement. Total variance explained by the multilevel contexts ranged from 15% to 22%. The influence of family SES on IQ and achievement overlapped substantially with the influence of school and neighborhood predictors. Together with race, the measured socioecological contexts explained 100% of shared environmental influences on IQ and approximately 79% of shared environmental influences on both verbal comprehension and reading ability. In contrast, nontrivial proportions of shared environmental variation in math performance were left unexplained. We highlight the potential utility of constructing “polyenvironmental risk scores” in an effort to better predict developmental outcomes and to quantify children's and adolescents’ interrelated networks of experiences. A video abstract of this article can be viewed at: https://youtu.be/77E_DctFsr0
Disasters, climate change, and securitisation: the United Nations Security Council and the United Kingdom's security policy
Authors: Peters Katie
Published: August 2018

Since climate change was included on the United Nations Security Council's agenda in 2007, there has been much debate about whether or not it has been securitised. This paper starts from the premise that climate change has undergone a partial securitisation—that is, a gradual process wherein political choices are made to frame certain issues in particular ways. Climate change has been reframed from a purely developmental and environmental concern to one that impels foreign policy and security domains. This paper makes a novel contribution to disasters, climate change, and security studies by arguing that explicit and implicit links to natural hazard‐related disasters have been employed as part of a gradual process of securitisation, or, more specifically, the partial securitisation of climate change. This is demonstrated by drawing on two cases: United Nations Security Council debates between 2007 and 2017; and the United Kingdom's security policy between 1997 and 2017.
Efficacy and safety of MYL‐1501D versus insulin glargine in patients with type 2 diabetes after 24 weeks: Results of the phase III INSTRIDE 2 study
Authors: Blevins Thomas C. , Barve Abhijit , Sun Bin , Raiter Yaron , Aubonnet Patrick , Muniz Rafael , Athalye Sandeep , Ankersen Michael
Published: August 2018

Aims

To assess the non‐inferiority of MYL‐1501D, a proposed biosimilar or follow‐on biological agent to marketed insulin glargine, to reference insulin glargine (Lantus®; Sanofi‐Aventis US LLC, Bridgewater, New Jersey) based on change in glycated hemoglobin (HbA1c).

Materials and methods

INSTRIDE 2 was a multicentre, open‐label, randomized, parallel‐group, phase III non‐inferiority study comparing the efficacy and safety of MYL‐1501D with those of reference insulin glargine in insulin‐naive and insulin‐non‐naive patients with type 2 diabetes mellitus receiving oral antidiabetic drugs (OADs). The primary efficacy endpoint was change in HbA1c from baseline to week 24. Secondary endpoints included metabolic readouts (eg, changes in fasting plasma glucose, insulin dosage, self‐monitored blood glucose), immunogenicity and adverse events, including hypoglycaemia and nocturnal hypoglycaemic events.

Results

In all, 560 patients were randomized to MYL‐1501D or insulin glargine in combination with OADs for 24 weeks. The mean change in HbA1c from baseline to week 24 was −0.60% (95% CI −0.78, −0.41) and − 0.66% (95% CI −0.84, −0.48) for MYL‐1501D and reference insulin glargine, respectively. MYL‐1501D was well tolerated and had a safety profile similar to that of reference insulin glargine.

Conclusions

Demonstration of non‐inferiority between MYL‐1501D and reference insulin glargine for reduction of HbA1c during 24 weeks of treatment was achieved. The two treatment groups were similar in terms of secondary endpoints, including hypoglycaemia and nocturnal hypoglycaemia, local and systemic reactions, other safety variables, and immunogenicity.
Contrasting effects of mosaic structure on alpha and beta diversity of bird assemblages in a human‐modified landscape
Authors: Neilan Wendy L. , Barton Philip S. , McAlpine Clive A. , Wood Jeffrey T. , Lindenmayer David B.
Published: August 2018

Habitat loss and fragmentation are key processes causing biodiversity loss in human‐modified landscapes. Knowledge of these processes has largely been derived from measuring biodiversity at the scale of ‘within‐habitat’ fragments with the surrounding landscape considered as matrix. Yet, the loss of variation in species assemblages ‘among’ habitat fragments (landscape‐scale) may be as important a driver of biodiversity loss as the loss of diversity ‘within’ habitat fragments (local‐scale). We tested the hypothesis that heterogeneity in vegetation cover is important for maintaining alpha and beta diversity in human‐modified landscapes. We surveyed bird assemblages in eighty 300‐m‐long transects nested within twenty 1‐km2 vegetation ‘mosaics’, with mosaics assigned to four categories defined by the cover extent and configuration of native eucalypt forest and exotic pine plantation. We examined bird assemblages at two spatial scales: 1) within and among transects, and 2) within and among mosaics. Alpha diversity was the mean species diversity within‐transects or within‐mosaics and beta diversity quantified the effective number of compositionally distinct transects or mosaics. We found that within‐transect alpha diversity was highest in vegetation mosaics defined by continuous eucalypt forest, lowest in mosaics of continuous pine plantation, and at intermediate levels in mosaics containing eucalypt patches in a pine matrix. We found that eucalypt mosaics had lower beta diversity than other mosaic types when ignoring relative abundances, but had similar or higher beta diversity when weighting with species abundances. Mosaics containing both pine and eucalypt forest differed in their bird compositional variation among transects, despite sharing a similar suite of species. This configuration effect at the mosaic scale reflected differences in vegetation composition among transects. Maintaining heterogeneity in vegetation cover could help to maintain variation among bird assemblages across landscapes, thus partially offsetting local‐scale diversity losses due to fragmentation. Critical to this is the retention of remnant native vegetation.
Evaluation of Paenibacillus polymyxa carboxymethylcellulose/poly (vinyl alcohol) formulation for control of Carya cathayensis canker caused by Botryosphaeria dothidea
Authors: Xu Sanger , Yao Junlei , Wu Fan , Mei Li , Wang Yongjun
Published: August 2018

Botryosphaeria trunk canker is arguably the most damaging disease of Carya cathayensis (Chinese hickory) in China. Fungicides are commonly applied to control the disease but have serious environmental issues. Here, the Gram‐positive bacterium Paenibacillus polymyxa strain CF05 was evaluated as an alternative for the preventive control of Botryosphaeria trunk canker on C. cathayensis. In vitro, this strain was inhibitory to the growth of B. dothidea, a causal agent of Chinese hickory trunk canker. Formulation of strain CF05 endospores in a carboxymethylcellulose/poly (vinyl alcohol) (CMC/PVA) blend showed high stability over a 12‐month period. A two‐year field experiment suggested that the CMC/PVA formulated strain CF05 reduced the occurrences of both new cankers and established cankers, displaying an efficacy comparable to treatment with thiophanate‐methyl. Furthermore, strain CF05 greatly induced production of phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO) and peroxidase (POX) by C. cathayensis seedlings, which showed maximum activity of these enzymes 2 days postinoculation (dpi) and increased phenol contents inside the trunk throughout the experimental assessment period. In summary, the P. polymyxa strain CF05 CMC/PVA formulation has promise as a potent environmentally friendly agent for the preventive biocontrol of C. cathayensis trunk canker.
Severe cytomegalovirus enterocolitis developing following daratumumab exposure in three patients with multiple myeloma
Authors: Lavi Noa , Okasha Doaa , Sabo Edmond , Oren Ilana , Benyamini Noam , Bar‐Yoseph Haggai
Published: August 2018

Objectives

The risk of cytomegalovirus (CMV) reactivation in multiple myeloma (MM) patients treated with bortezomib‐based induction regimens is increased following autologous stem cell transplantation (ASCT). There is paucity of data regarding the risk of CMV infections in MM patients who did not receive bortezomib and ASCT.

Methods

We herein report three cases of heavily pretreated MM patients, receiving daratumumab‐containing combination regimens, in whom ASCT had been performed long ago and who recently developed severe CMV‐related gastrointestinal disease.

Results

All the three patients had a prolonged CMV disease course requiring a long‐term antiviral treatment. All the patients suffered from CMV colitis. One patient had concurrent CMV duodenitis and another patient had a concurrent CMV retinitis.

Conclusion

Novel myeloma treatments prolong patient survival and more patients with profound immunosuppression following multiple lines of therapies are seen in clinical practice. These patients may present with opportunistic infections that were rare in the past. Our findings suggest a possible association between daratumumab therapy (in combination with other immunosuppressive therapies) and severe CMV gastrointestinal disease. A longer follow‐up is needed to explore long‐term side effects of novel agents like daratumumab in newly diagnosed as well as heavily pretreated MM patients.