bluuebunny/crossref_metadata_2025 huggingface dataset:
Antecedents and neuroimaging patterns in cerebral palsy with epilepsy and cognitive impairment: a population‐based study in children born at term
Authors: Ahlin Kristina , Jacobsson Bo , Nilsson Staffan , Himmelmann Kate
Published: March 2017

Introduction

Antecedents of accompanying impairments in cerebral palsy and their relation to neuroimaging patterns need to be explored.

Material and methods

A population‐based study of 309 children with cerebral palsy born at term between 1983 and 1994. Prepartum, intrapartum, and postpartum variables previously studied as antecedents of cerebral palsy type and motor severity were analyzed in children with cerebral palsy and cognitive impairment and/or epilepsy, and in children with cerebral palsy without these accompanying impairments. Neuroimaging patterns and their relation to identified antecedents were analyzed. Data were retrieved from the cerebral palsy register of western Sweden, and from obstetric and neonatal records.

Results

Children with cerebral palsy and accompanying impairments more often had low birthweight (kg) (odds ratio 0.5, 95% confidence interval 0.3–0.8), brain maldevelopment known at birth (p = 0.007, odds ratio ∞) and neonatal infection (odds ratio 5.4, 95% confidence interval 1.04–28.4). Moreover, neuroimaging patterns of maldevelopment (odds ratio 7.2, 95% confidence interval 2.9–17.2), cortical/subcortical lesions (odds ratio 5.3, 95% confidence interval 2.3–12.2) and basal ganglia lesions (odds ratio 7.6, 95% confidence interval 1.4–41.3) were more common, wheras white matter injury was found significantly less often (odds ratio 0.2, 95% confidence interval 0.1–0.5). In most children with maldevelopment, the intrapartum and postpartum periods were uneventful (p < 0.05). Cerebral maldevelopment was associated with prepartum antecedents, whereas subcortical/cortical and basal ganglia lesions were associated with intrapartum and postpartum antecedents.

Conclusion

No additional factor other than those related to motor impairment was associated with epilepsy and cognitive impairment in cerebral palsy. Timing of antecedents deemed important for the development of cerebral palsy with accompanying impairments were supported by neuroimaging patterns.
Probiotics and antimicrobial protein and peptide levels in preterm infants
Authors: Strunk Tobias , Hibbert Julie , Doherty Dorota , Granland Caitlyn , Trend Stephanie , Simmer Karen , Burgner David , Patole Sanjay , Currie Andrew
Published: March 2017

Aim

To characterise the secreted and inducible antimicrobial protein and peptide (APP) levels in a prospective cohort of preterm infants (<30 weeks gestational age) with or without Bifidobacterium breve M16V supplementation during the first month of life.

Methods

We analysed serial biosamples of infants who did (n = 13) or did not receive (n = 62) B. breve (3 × 109 cfu/day). Peripheral blood was obtained on days 1, 14 and 28, and infant stool prior to commencement of probiotic supplementation and on day 21. Levels of APP (bactericidal/permeability inducing protein (BPI), beta defensins 1 and 2, lactoferrin, human cathelicidin, secretory phospholipase A2) in plasma and stool were determined. Further, we characterised induced APP levels in whole blood cultured with live S. epidermidis or with agonists of Toll‐like receptors 2/6 and 4.

Results

Stool, plasma and stimulated blood APP levels changed significantly during the first month of life. Supplementation with B. breve did not affect basal or stimulated APP levels except for a transient increase in inducible BPI.

Conclusion

Supplementation with B. breve does not appear to act via modulation of systemic or enteric APP expression in preterm infants although small effects cannot be excluded. Further work with other probiotic preparations is warranted.
Systematic review of nonpharmacological analgesic interventions for common needle‐related procedure in newborn infants and development of evidence‐based clinical guidelines
Authors: Lago Paola , Garetti Elisabetta , Bellieni Carlo Valerio , Merazzi Daniele , Savant Levet Patrizia , Ancora Gina , Pirelli Anna ,   the Pain Study Group of the Italian Society of Neonatology
Published: March 2017

The aim of this literature review was to develop clinical guidelines for the prevention and control of needle‐related pain in newborn infants. The guidelines were developed by the Italian Society of Neonatology, using the Grading of Recommendations, Assessment, Development and Evaluation approach, based on the assessment of 232 papers published between 1986 and 2015. The quality of the evidence was high or moderate for some behavioural and nonpharmacological interventions.

Conclusion

There was sufficient evidence to strongly support the use of nonpharmacological interventions for common needle‐related procedures in newborn infants. Combined interventions seemed to be more effective in relieving procedural pain.
Higher growth, fat and fat‐free masses correlate with larger cerebellar volumes in preterm infants at term
Authors: Paviotti Giulia , De Cunto Angela , Zennaro Floriana , Boz Giulia , Travan Laura , Cont Gabriele , Bua Jenny , Demarini Sergio
Published: March 2017

Aim

Smaller cerebellar volumes in very low‐birthweight (VLBW) infants at term have been related to adverse cognitive outcomes, and this study evaluated whether these volumes were associated with a growth in body composition during hospital stays.

Methods

We prospectively recruited 42 VLBW infants from an Italian neonatal unit between January 2013 and August 2015. Cerebellar volumes and body composition were measured by magnetic resonance imaging (MRI) and air‐displacement plethysmography, respectively, at 40 weeks of gestational age and anthropometric and nutritional data were collected. We also included 20 term‐born controls.

Results

The mean gestational age and birthweight of the VLBW infants were 29.4 (±1.9) weeks and 1120 (±290) g. There was a positive correlation between cerebellar volumes and daily weight gain from birth to term (R2 = 0.26, p = 0.001), weight (R2 = 0.25, p = 0.001), length (R2 = 0.16, p = 0.01), fat mass (R2 = 0.15, p = 0.01) and fat‐free mass at term (R2 = 0.20, p = 0.003). In multiple regression analysis, daily weight gain, mechanical ventilation and postconceptional age at MRI were independently associated with cerebellar volumes. Anthropometric data and cerebellar volumes were similar between VLBW and control infants.

Conclusion

Higher growth, higher fat mass and fat‐free mass were associated with larger cerebellar volumes in VLBW infants at term.
Child survival revolutions revisited – lessons learned from Bangladesh, Nicaragua, Rwanda and Vietnam
Authors: Persson Lars Åke , Rahman Anisur , Peña Rodolfo , Perez Wilton , Musafili Aimable , Hoa Dinh Phuong
Published: March 2017

Analysing child mortality may enhance our perspective on global achievements in child survival. We used data from surveillance sites in Bangladesh, Nicaragua and Vietnam and Demographic Health Surveys in Rwanda to explore the development of neonatal and under‐five mortality. The mortality curves showed dramatic reductions over time, but child mortality in the four countries peaked during wars and catastrophes and was rapidly reduced by targeted interventions, multisectorial development efforts and community engagement.

Conclusion: Lessons learned from these countries may be useful when tackling future challenges, including persistent neonatal deaths, survival inequalities and the consequences of climate change and migration.
Auditory impairment in infants with neonatal chronic lung disease is alleviated after term
Authors: Jiang Ze D.
Published: March 2017

Aim

Very premature infants with neonatal chronic lung disease (CLD) have been reported to have major auditory impairment at term, and we examined the outcomes in 30 infants after term age.

Methods

Brainstem auditory evoked response (BAER) was recorded at a postconceptional age of 46–61 weeks in 13 CLD cases and 14 controls from China and 17 CLD cases and 22 controls from the UK.

Results

The BAER threshold in the CLD infants was slightly higher. Clicks at the normal hearing level (60 dB) showed no significant differences between the cases and controls in the latencies of BAER waves I, III and V and the I–V interval. However, the CLD infants demonstrated marginal shortening in the I‐III interval and a marginal increase in the III‐V interval. The amplitudes of BAER waves in the CLD infants were all slightly smaller than the controls. At 70 and 40 dB normal hearing level, the BAER findings were similar to those obtained at 60 dB normal hearing level, with only small variations.

Conclusion

There were minor BAER abnormalities in the CLD infants, suggesting minor auditory impairment. The auditory impairment previously detected at the term date was later alleviated.
Moderate grazing sustains plant diversity in Afromontane grassland
Authors: Joubert Lize , Pryke James S. , Samways Michael J.
Published: March 2017

Aims

Natural disturbances drive plant assemblages in Afromontane grassland. Our aim is to assess how intensity of cattle grazing and time since last fire influence plant species richness, dominance and assemblage composition.

Location

Central Midlands, KwaZulu‐Natal province, South Africa.

Methods

Sites differed in grazing intensity (light, moderate and heavy) and time since last fire: recently burned (RB) vs unburned (UB). We sampled plants in 24 vegetation quadrats (1‐m2) randomly located within each site (~1000 m2). We used linear regression models for species richness and dominance, IndVal to identify indicator species and CCA for assemblage composition. All analyses were conducted at quadrat and site level.

Results

Species richness was significantly influenced by time since last fire (RB > UB), grazing intensity (light < moderate > heavy) and the fire–grazing interaction at quadrat level. Dominance reciprocated the response of species richness to time since last fire (UB > RB), but did not respond consistently to grazing intensity (light > moderate > or < heavy). Plant assemblage composition was significantly influenced by time since last fire, grazing intensity and vegetation structure (live vegetation cover and vegetation height). Indicator species of species‐poor, heavily grazed sites included alien species, such as Cirsium vulgare and Conyza bonariensis.

Conclusion

Response of species richness to grazing intensity conforms to the predictions of the intermediate disturbance hypothesis. Burning and moderate grazing should be part of grassland management. To prevent species loss and influx of alien species, heavy grazing should be minimized. As development of grassland ecological networks in a timber matrix is being pioneered in South Africa, these findings indicate a way forward for the management of similar systems elsewhere in the world.
CCL20 neutralization by a monoclonal antibody in healthy subjects selectively inhibits recruitment of CCR6+ cells in an experimental suction blister
Authors: Bouma Gerben , Zamuner Stefano , Hicks Kirsty , Want Andrew , Oliveira João , Choudhury Arpita , Brett Sara , Robertson Darren , Felton Leigh , Norris Virginia , Fernando Disala , Herdman Michael , Tarzi Ruth
Published: March 2017

Aims

GSK3050002, a humanized IgG1κ antibody with high binding affinity to human CCL20, was administered in a first‐in‐human study to evaluate safety, pharmacokinetics (PK) and pharmacodynamics (PD). An experimental skin suction blister model was employed to assess target engagement and the ability of the compound to inhibit recruitment of inflammatory CCR6 expressing cells.

Methods

This study was a randomized, double‐blind (sponsor open), placebo‐controlled, single‐centre, single ascending intravenous dose escalation trial in 48 healthy male volunteers.

Results

GSK3050002 (0.1–20 mg kg−1) was well tolerated and no safety concerns were identified. The PK was linear over the dose range, with a half‐life of approximately 2 weeks. Complex of GSK3050002/CCL20 increased in serum and blister fluid with increasing doses of GSK3050002. There were dose‐dependent decreases in CCR6+ cell recruitment to skin blisters with maximal effects at doses of 5 mg kg−1 and higher, doses at which GSK3050002/CCL20 complex in serum and blister fluid also appeared to reach maximum levels.

Conclusions

These results indicate a relationship between PK, target engagement and PD, suggesting a selective inhibition of recruitment of CCR6+ cells by GSK3050002 and support further development of GSK3050002 in autoimmune and inflammatory diseases.
A population pharmacokinetic meta‐analysis of custirsen, an antisense oligonucleotide, in oncology patients and healthy subjects
Authors: Edwards Alena Y. , Elgart Anna , Farrell Colm , Barnett‐Griness Ofra , Rabinovich‐Guilatt Laura , Spiegelstein Ofer
Published: March 2017

Aims

Custirsen (OGX‐011/TV‐1011), a second‐generation antisense oligonucleotide that reduces clusterin production, is under investigation with chemotherapy in prostate and lung cancer. This meta‐analysis evaluated the population pharmacokinetics (PK) of custirsen in cancer patients and healthy subjects.

Methods

The population PK analysis used custirsen plasma concentrations from five Phase 1 studies, one Phase 1/2 study, and one Phase 3 study in two stages. Cancer patients received multiple doses of custirsen (40–640 mg intravenously over 120 min) with chemotherapy; healthy subjects received single or multiple doses (320–640 mg). An interim population PK model was developed using a nonlinear mixed‐effect approach incorporating data from four Phase 1 or 1/2 studies, followed by model refinement and inclusion of two Phase 1 and one Phase 3 studies.

Results

The final model was developed with 5588 concentrations from 631 subjects with doses of 160–640 mg. Custirsen PK was adequately described by a three‐compartment model with first‐order elimination. For a representative 66‐year‐old individual with body weight 82 kg and serum creatinine level 0.933 mg dl−1, the estimated typical (95% CI) parameter values were clearance (CL) = 2.36 (2.30–2.42) l h−1, central volume of distribution (V1) = 6.08 (5.93–6.23) l, peripheral volume of distribution (V2) = 1.13 (1.01–1.25) l, volume of the second peripheral compartment (V3) = 15.8 (14.6–17.0) l, inter‐compartmental clearance Q2 = 0.0755 (0.0689–0.0821) l h−1, and Q3 = 0.0573 (0.0532–0.0614) l h−1. Age, weight and serum creatinine were predictors of CL; age was a predictor of Q3.

Conclusion

A population PK model for custirsen was successfully developed in cancer patients and healthy subjects, including covariates contributing to variability in custirsen PK.
Potential of bisbenzimidazole‐analogs toward metronidazole‐resistant Trichomonas vaginalis isolates
Authors: Korosh Travis , Bujans Emmanuel , Morada Mary , Karaalioglu Canan , Vanden Eynde Jean Jacques , Mayence Annie , Huang Tien L. , Yarlett Nigel
Published: March 2017

A bisoxyphenylene‐bisbenzimidazole series with increasing aliphatic chain length (CH2 to C10H20) containing a meta‐ (m) or para (p)‐benzimidazole linkage to the phenylene ring was tested for ability to inhibit the growth of metronidazole‐susceptible (C1) and metronidazole‐refractory (085) Trichomonas vaginalis isolates under aerobic and anaerobic conditions. Compound 3m, 2,2′‐[α,ω‐propanediylbis(oxy‐1,3‐phenylene)]bis‐1H‐benzimidazole, displayed a 5.5‐fold lower minimum inhibitory concentration (MIC) toward T. vaginalis isolate 085 than metronidazole under aerobic growth conditions, (26 μm compared to 145 μm). A dose of 25 mg/kg per day for four days of compound 3m cured a subcutaneous mouse model infection using T. vaginalis isolates 286 (metronidazole susceptible) and 085 (metronidazole refractory). Compound 3m was weakly reduced by pyruvate:ferredoxin oxidoreductase, but unlike metronidazole was not dependent upon added ferredoxin. It is concluded from structure‐activity relationships that there was no obvious trend based on the length of the central aliphatic chain, or the steric position of the bisbenzimidazole enabling prediction of biological activity. The compounds generally fulfill Lipinski's rile of five, indicating their potential as drug leads.
Pharmacokinetics of prolonged‐release tacrolimus versus immediate‐release tacrolimus in de novo liver transplantation: A randomized phase III substudy
Authors: Ericzon Bo‐Göran , Varo Evaristo , Trunečka Pavel , Fischer Lutz , Colledan Michele , Gridelli Bruno , Valdivieso Andrés , O'Grady John , Dickinson James , Undre Nasrullah
Published: March 2017

Background

With the same dose of tacrolimus, lower systemic exposure on the first day of dosing has been reported for prolonged‐release tacrolimus compared with immediate‐release tacrolimus, prompting investigation of differing initial doses.

Methods

This substudy of a double‐blind, randomized, phase III trial in de novo liver transplant recipients compared the pharmacokinetics of once‐daily prolonged‐release tacrolimus (initial dose: 0.2 mg/kg/day) versus twice‐daily immediate‐release tacrolimus (initial dose: 0.1 mg/kg/day) during the first 2 weeks post‐transplant.

Results

Pharmacokinetic data were analyzed from patients receiving prolonged‐release tacrolimus (n=13) and immediate‐release tacrolimus (n=12). Mean systemic exposure (AUC0‐24) was higher with prolonged‐release versus immediate‐release tacrolimus. Dose‐normalized AUC0‐24 (normalized to 0.1 mg/kg/day) showed generally lower exposure with prolonged‐release tacrolimus versus immediate‐release tacrolimus. There was good correlation between AUC0‐24 and concentration at 24 hours after the morning dose (r=.96 and r=.86, respectively), and the slope of the line of best fit was similar for both formulations.

Conclusions

Doubling the initial starting dose of prolonged‐release tacrolimus compared with immediate‐release tacrolimus overcompensated for lower exposure on Day 1. A 50% higher starting dose of prolonged‐release tacrolimus than immediate‐release tacrolimus may be required for similar systemic exposure. However, doses of both formulations can be optimized using the same trough‐level monitoring system. (ClinicalTrials.gov number: NCT00189826).
Factors determining uptake of diabetic retinopathy screening in Oxfordshire
Authors: Moreton R. B. R. , Stratton I. M. , Chave S. J. , Lipinski H. , Scanlon P. H.
Published: March 2017

Aims

To investigate variables at the demographic and primary care practice levels that influence the uptake of diabetic retinopathy screening.

Methods

Data were extracted from the management software of one screening programme for 21 797 people registered with 79 general practices. Uptake was examined by gender, age group, modality of screening (mobile unit at general practice versus high‐street optometrist), and by general practice. A telephone survey of high‐street optometrists provided information on the availability of screening appointments.

Results

Uptake was 82.4% during the study period, and was higher for men (83.2%) than for women (81.5%) (P = 0.001). Uptake varied by age group (P < 0.001), being lowest in those aged 12–39 years (67%). Uptake was higher for people invited to a general practice for screening by a mobile unit (83.5%) than for those invited for screening by a high‐street optometrist (82%) (P = 0.006). After adjusting for these factors and for socio‐economic deprivation score at the location of the general practice, heterogeneity in uptake rate was still observed between some practices. Our survey of optometrists indicated wide variation in the availability of time slots for screening during the week and of screening appointment provision.

Conclusions

Diabetic retinopathy screening services do not achieve high uptake among the youngest or oldest age groups. Practices in the least deprived areas had the highest uptake. Variation in uptake between general practices after adjustment for individual‐level variables and deprivation suggests that practice‐level factors may have an important role in determining rates of screening attendance.
Effects of quantitative and qualitative differences in volatiles from host‐ and non‐host‐infested maize on the attraction of the larval parasitoid Cotesia kariyai
Authors: Thanikkul Ploypilin , Piyasaengthong Narisara , Menezes‐Netto Alexandre Carlos , Taylor DeMar , Kainoh Yooichi
Published: March 2017

Cotesia kariyai Watanabe (Hymenoptera: Braconidae) is a specialist larval parasitoid of Mythimna separata Walker (Lepidoptera: Noctuidae). Cotesia kariyai wasps use herbivore‐induced plant volatiles (HIPVs) to locate hosts. However, complex natural habitats are full of volatiles released by both herbivorous host‐ and non‐host‐infested plants at various levels of intensity. Therefore, the presence of non‐hosts may affect parasitoid decisions while foraging. Here, the host‐finding efficiency of naive C. kariyai from HIPVs influenced by host‐ and non‐host‐infested maize [Zea mays L. (Poaceae)] plants was investigated with a four‐arm olfactometer. Ostrinia furnacalis Guenée (Lepidoptera: Crambidae) was selected as a non‐host species. One unit (1 U) of host‐ or non‐host‐infested plant was prepared by infesting a potted plant with five host or seven non‐host larvae. In two‐choice bioassays, host‐infested plants fed upon by different numbers of larvae, and various units of host‐ and non‐host‐infested plants (infestation units; 1 U, 2 U, and 3 U) were arranged to examine the effects of differences in volatile quantity and quality on the olfactory responses of C. kariyai with the assumption that volatile quantity and quality changes with differences in numbers of insects and plants. Cotesia kariyai was found to perceive quantitative differences in volatiles from host‐infested plants, preferring larger quantities of volatiles from larger numbers of larvae or plants. Also, the parasitoids discriminated between healthy plants, host‐infested plants, and non‐host‐infested plants by recognising volatiles released from those plants. Cotesia kariyai showed a reduced preference for host‐induced volatiles, when larger numbers of non‐host‐infested plants were present. Therefore, quantitative and qualitative differences in volatiles from host‐ and non‐host‐infested plants appear to affect the decision of C. kariyai during host‐habitat searching in multiple tritrophic systems.
Carfilzomib‐containing combinations as frontline therapy for multiple myeloma: A meta‐analysis of 13 trials
Authors: Sheng Zhixin , Li Guifang , Li Bin , Liu Yanju , Wang Lida
Published: March 2017

Objective

To investigate the activity and safety of carfilzomib‐containing combinations as frontline therapy for multiple myeloma.

Methods

We searched published carfilzomib reports for newly diagnosed multiple myeloma.

Results

Thirteen trials were identified, covering 704 subjects. Pooled analysis showed that carfilzomib combinations as frontline therapy for multiple myeloma attained an impressive at least complete response (≥CR) rate of 21%, at least very good partial response (≥VGPR) rate of 68%, overall response rate (ORR) of 94%. The ≥CR rates of 18% pre‐SCT were increased to 43% of post‐ASCT, and 64% of postconsolidation (P<.001). For those patients receiving carfilzomib therapy, response quality improved further over time (≥CR rates of 10% after 2nd cycle, 20% after 4th cycle, 43% after 8th cycle; ≥VGPR of 29% after 2nd cycle, 68% after 4th cycle, 88% after 8th cycle). ≥CR rates of 49% from CFZ‐LEN‐DEX triplet regimen were higher than 18% from CFZ‐CYC‐DEX triplet regimen and 21% from CFZ‐THA‐DEX triplet regimen (P=.03).

Conclusions

Carfilzomib combinations could produce clinical benefits in newly diagnosed patients with multiple myeloma. High‐quality response rate could be further improved through ASCT, consolidation therapy, and more cycles of chemotherapy even in the era of carfilzomib. CFZ‐LEN‐DEX could be a good combination regimen.
Multidirectional abundance shifts among North American birds and the relative influence of multifaceted climate factors
Authors: Huang Qiongyu , Sauer John R. , Dubayah Ralph O.
Published: March 2017

Shifts in species distributions are major fingerprint of climate change. Examining changes in species abundance structures at a continental scale enables robust evaluation of climate change influences, but few studies have conducted these evaluations due to limited data and methodological constraints. In this study, we estimate temporal changes in abundance from North American Breeding Bird Survey data at the scale of physiographic strata to examine the relative influence of different components of climatic factors and evaluate the hypothesis that shifting species distributions are multidirectional in resident bird species in North America. We quantify the direction and velocity of the abundance shifts of 57 permanent resident birds over 44 years using a centroid analysis. For species with significant abundance shifts in the centroid analysis, we conduct a more intensive correlative analysis to identify climate components most strongly associated with composite change of abundance within strata. Our analysis focus on two contrasts: the relative importance of climate extremes vs. averages, and of temperature vs. precipitation in strength of association with abundance change. Our study shows that 36 species had significant abundance shifts over the study period. The average velocity of the centroid is 5.89 km·yr−1. The shifted distance on average covers 259 km, 9% of range extent. Our results strongly suggest that the climate change fingerprint in studied avian distributions is multidirectional. Among 6 directions with significant abundance shifts, the northwestward shift was observed in the largest number of species (n = 13). The temperature/average climate model consistently has greater predictive ability than the precipitation/extreme climate model in explaining strata‐level abundance change. Our study shows heterogeneous avian responses to recent environmental changes. It highlights needs for more species‐specific approaches to examine contributing factors to recent distributional changes and for comprehensive conservation planning for climate change adaptation.
Ureteroenteric anastomotic revision as initial management of stricture after urinary diversion
Authors: Gin Greg E , Ruel Nora H , Parihar Jaspreet S , Warner Jonathan N , Yuh Bertram E , Yamzon Jonathan , Wilson Timothy G , Lau Clayton S , Chan Kevin G
Published: March 2017

Objective

To report our experience with ureteroenteric anastomotic revision as initial treatment of stricture after urinary diversion.

Methods

An institutional review board‐approved retrospective study was carried out. A total of 41 patients who underwent primary ureteroenteric anastamotic revision were identified between 2007 and 2015. Data analyzed included patient characteristics, type of diversion, estimated blood loss, operative time, change in renal function, length of stay, postoperative complications and time with nephrostomy/stent. Success of revision was defined as an improvement in hydronephrosis on radiographic imaging and/or reflux during pouchogram. Predictors of length of stay and complications were analyzed using analysis of covariance.

Results

A total of 50 renal units were revised with a success rate of 100%. The median length of stay was 6 days (2–16 days). There were a total of 15 complications (one major, 14 minor) in 14 patients (33% 30‐day complication rate). The most common were wound infection (n = 4) and arrhythmia (n = 4). Robotic revision (n = 5) had a median length of stay of 3 days (2–4) with no complications.

Conclusions

Primary ureteroenteric anastomotic revisions have an excellent success rate at an experienced center and might obviate the need for multiple interventions. Open revision is associated with mostly minor complications. Robotic revision might reduce the morbidity of open revision in select cases.
PAI1: a novel PP1‐interacting protein that mediates human plasma's anti‐apoptotic effect in endothelial cells
Authors: Yao Hui , He Guangchun , Chen Chao , Yan Shichao , Lu Lu , Song Liujiang , Vijayan K. Vinod , Li Qinglong , Xiong Li , Miao Xiongying , Deng Xiyun
Published: March 2017

Activation of apoptotic signalling in endothelial cells contributes to the detrimental effects of a variety of pathological stimuli. In investigating the molecular events underlying the anti‐apoptotic effect of human plasma in cultured human endothelial cells, we unexpectedly uncovered a novel mechanism of apoptosis suppression by human plasma through an interaction between two previously unrelated proteins. Human plasma inhibited hypoxia–serum deprivation‐induced apoptosis and stimulated BADS136 and AktS473 phosphorylation. Akt1 silencing reversed part (~52%) of the anti‐apoptotic effect of human plasma, suggesting the existence of additional mechanisms mediating the anti‐apoptotic effect other than Akt signalling. Human plasma disrupted the interaction of BAD with protein phosphatase 1 (PP1). Mass spectrometry identified fourteen PP1‐interacting proteins induced by human plasma. Notably, a group of serine protease inhibitors including plasminogen activator inhibitor 1 (PAI1), a major inhibitor of fibrinolysis, were involved. Silencing of PAI1 attenuated the anti‐apoptotic effect of human plasma. Furthermore, combined Akt1 and PAI1 silencing attenuated the majority of the anti‐apoptotic effect of human plasma. We conclude that human plasma protects against endothelial cell apoptosis through sustained BAD phosphorylation, which is achieved by, at least in part, a novel interaction between PP1 with PAI1.
Improved classification of indeterminate biliary strictures by probe‐based confocal laser endomicroscopy using the Paris Criteria following biliary stenting
Authors: Taunk Pushpak , Singh Satish , Lichtenstein David , Joshi Virendra , Gold Jason , Sharma Ashish
Published: March 2017

Background and Aims

Probe‐based confocal laser endomicroscopy (pCLE) using the Miami Criteria has improved classification of indeterminate biliary strictures. However, previous biliary stenting may result in their misclassification as malignant strictures. Inflammatory criteria were added to form the Paris Classification to prevent this misclassification and reduce false positives. The aim of this study was to assess if the Paris Classification was more accurate than the Miami Classification in classifying indeterminate biliary strictures after biliary stenting.

Methods

This was a retrospective observational study involving 21 patients with indeterminate biliary strictures from whom 27 pCLE video sequences were obtained (20 benign and seven malignant). Patients with and without prior biliary stenting underwent pCLE. Two investigators classified the strictures as malignant or benign using the Miami and Paris Classifications. Diagnostic accuracy, sensitivity (Se), and specificity (Sp) of endoscopic retrograde‐guided pCLE were compared with final histopathology.

Results

In those without biliary stenting, the Miami Criteria resulted in Se 88%, Sp 75%, positive predictive value (PPV) 64%, negative predictive value (NPV) 92%, and accuracy 79%, while the Paris Classification resulted in Se 63%, Sp 88%, PPV 71%, NPV 82%, and accuracy 79%. In those with prior biliary stenting, the Miami Criteria resulted in Se 88%, Sp 36%, PPV 23%, NPV 93%, and accuracy 45%, while the Paris Classification resulted in Se 63%, Sp 73%, PPV 31%, NPV 91%, and accuracy 71%. The kappa statistic was 0.56.

Conclusion

The Paris Classification improved specificity and accuracy of biliary stricture classification in those who had been previously stented and decreased the rate of misclassification of benign strictures as malignant.
A Systematic Review of Gay, Lesbian, and Bisexual Research Samples in Couple and Family Therapy Journals
Authors: Hartwell Erica E. , Serovich Julianne M. , Reed Sandra J. , Boisvert Danielle , Falbo Teresa
Published: March 2017

The purpose of this study is to review samples from research on gay, lesbian, and bisexual (GLB) issues and to evaluate the suitability of this body of research to support affirmative and evidence‐based practice with GLB clients. The authors systematically reviewed the sampling methodology and sample composition of GLB‐related research. All original, quantitative articles focusing on GLB issues published in couple and family therapy (CFT)‐related journals since 1975 were coded (n = 153). Results suggest that within the GLB literature base there is some evidence of heterocentrism as well as neglect of issues of class, race, and gender. Suggestions to improve the diversity and representativeness of samples—and, thus, clinical implications—of GLB‐related research in CFT literature are provided.
Innovation with Limited Resources: Management Lessons from theGermanMittelstand
Authors: De Massis Alfredo , Audretsch David , Uhlaner Lorraine , Kammerlander Nadine
Published: March 2017

German Mittelstand firms are globally recognized for their innovation, especially regarding product, process, and service innovation. So what can scholars and managers across the globe learn from the success story of German Mittelstand innovation? Drawing on information collected on innovative Mittelstand firms and extant knowledge on innovation, the resource‐based view, and family firm research, the authors investigate how these highly innovative firms flourish and achieve high innovation performance despite the severe financial and human capital resource constraints they face as compared with larger corporations. The authors then present a model identifying and integrating six salient traits of such firms that allow them to efficiently orchestrate their resources to innovate and outcompete their competitors in the global market, enabling those firms to overcome their resource‐related weaknesses and turn them into strengths. Specifically, these traits are: niche focus and customer collaboration, globalization strategy, preference for self‐financing, long‐run mindset, superior employee relations, and community embeddedness. The power of this Mittelstand approach takes full effect only when all six traits operate in an integrated fashion, and the proposed resource‐based model serves as a starting point for a more holistic and comprehensive understanding of firm ability to innovate and successfully compete within a specific context. The article outlines the implications of the model of German Mittelstand innovation for research conducted in different fields including innovation, entrepreneurship, strategy, dynamic capabilities, ecosystems, and family business. Finally, the article proposes a future research agenda aimed at improving current understanding of the German Mittelstand “innovation strategy” and its transferability to other contexts, and outlines practical implications for owners and managers worldwide wanting to emulate the German Mittelstand innovation model.
Molecular phylogeny and taxonomic revision of the genus Wittrockiella (Pithophoraceae, Cladophorales), including the descriptions of W. australis sp. nov. and W. zosterae sp. nov.
Authors: Boedeker Christian , O'Kelly Charles J. , West John A. , Hanyuda Takeaki , Neale Adele , Wakana Isamu , Wilcox Mike D. , Karsten Ulf , Zuccarello Giuseppe C.
Published: March 2017

Wittrockiella is a small genus of filamentous green algae that occurs in habitats with reduced or fluctuating salinities. Many aspects of the basic biology of these algae are still unknown and the phylogenetic relationships within the genus have not been fully explored. We provide a phylogeny based on three ribosomal markers (ITS, LSU, and SSU rDNA) of the genus, including broad intraspecific sampling for W. lyallii and W. salina, recommendations for the use of existing names are made, and highlight aspects of their physiology and life cycle. Molecular data indicate that there are five species of Wittrockiella. Two new species, W. australis and W. zosterae, are described, both are endophytes. Although W. lyallii and W. salina can be identified morphologically, there are no diagnostic morphological characters to distinguish between W. amphibia, W. australis, and W. zosterae. A range of low molecular weight carbohydrates were analyzed but proved to not be taxonomically informative. The distribution range of W. salina is extended to the Northern Hemisphere as this species has been found in brackish lakes in Japan. Furthermore, it is shown that there are no grounds to recognize W. salina var. kraftii, which was described as an endemic variety from a freshwater habitat on Lord Howe Island, Australia. Culture experiments indicate that W. australis has a preference for growth in lower salinities over full seawater. For W. amphibia and W. zosterae, sexual reproduction is documented, and the split of these species is possibly attributable to polyploidization.
A rare case of plastid protein‐coding gene duplication in the chloroplast genome of Euglena archaeoplastidiata (Euglenophyta)
Authors: Bennett Matthew S. , Shiu Shin‐Han , Triemer Richard E.
Published: March 2017

Gene duplication is an important evolutionary process that allows duplicate functions to diverge, or, in some cases, allows for new functional gains. However, in contrast to the nuclear genome, gene duplications within the chloroplast are extremely rare. Here, we present the chloroplast genome of the photosynthetic protist Euglena archaeoplastidiata. Upon annotation, it was found that the chloroplast genome contained a novel tandem direct duplication that encoded a portion of RuBisCO large subunit (rbcL) followed by a complete copy of ribosomal protein L32 (rpl32), as well as the associated intergenic sequences. Analyses of the duplicated rpl32 were inconclusive regarding selective pressures, although it was found that substitutions in the duplicated region, all non‐synonymous, likely had a neutral functional effect. The duplicated region did not exhibit patterns consistent with previously described mechanisms for tandem direct duplications, and demonstrated an unknown mechanism of duplication. In addition, a comparison of this chloroplast genome to other previously characterized chloroplast genomes from the same family revealed characteristics that indicated E. archaeoplastidiata was probably more closely related to taxa in the genera Monomorphina, Cryptoglena, and Euglenaria than it was to other Euglena taxa. Taken together, the chloroplast genome of E. archaeoplastidiata demonstrated multiple characteristics unique to the euglenoid world, and has justified the longstanding curiosity regarding this enigmatic taxon.
Early Devonian (~410 mya) microfossils resembling Characiopsis (Tribophyceae) and Characium (Chlorophyceae)
Authors: Krings Michael , Harper Carla J. , Taylor Edith L. , Kerp Hans
Published: March 2017

Unusual microfossils that occurred associated with fungal spores in the Lower Devonian (~410 mya) Windyfield chert from Scotland were composed of a narrow stipe (2.5–9 μm long) to which was attached an obovoid or elongate drop‐shaped cell up to 14 μm long; a basal attachment pad was present in several specimens. The fossils were strikingly similar morphologically to certain present‐day unicellular freshwater Tribophyceae and Chlorophyceae, but affinities to the fungal phylum Chytridiomycota also cannot be ruled out. This discovery adds to the inventory of distinctive microbial morphologies in the early non‐marine paleoecosystems.
Interspecific hybridization causes long‐term phylogenetic discordance between nuclear and mitochondrial genomes in freshwater fishes
Authors: Wallis Graham P. , Cameron‐Christie Sophia R. , Kennedy Hannah L. , Palmer Gemma , Sanders Tessa R. , Winter David J.
Published: March 2017

Classification, phylogeography and the testing of evolutionary hypotheses rely on correct estimation of species phylogeny. Early molecular phylogenies often relied on mtDNAalone, which acts as a single linkage group with one history. Over the last decade, the use of multiple nuclear sequences has often revealed conflict among gene trees. This observation can be attributed to hybridization, lineage sorting, paralogy or selection. Here, we use 54 groups of fishes from 48 studies to estimate the degree of concordance between mitochondrial and nuclear gene trees in two ecological grades of fishes: marine and freshwater. We test the hypothesis that freshwater fish phylogenies should, on average, show more discordance because of their higher propensity for hybridization in the past. In keeping with this idea, concordance between mitochondrial and nuclear gene trees (as measured by proportion of components shared) is on average 50% higher in marine fishes. We discuss why this difference almost certainly results from introgression caused by greater historical hybridization among lineages in freshwater groups, and further emphasize the need to use multiple nuclear genes, and identify conflict among them, in estimation of species phylogeny.
Chasing ghosts: allopolyploid origin of Oxyria sinensis (Polygonaceae) from its only diploid congener and an unknown ancestor
Authors: Luo Xin , Hu Quanjun , Zhou Pingping , Zhang Dan , Wang Qian , Abbott Richard J. , Liu Jianquan
Published: March 2017

Reconstructing the origin of a polyploid species is particularly challenging when an ancestor has become extinct. Under such circumstances, the extinct donor of a genome found in the polyploid may be treated as a ‘ghost’ species in that its prior existence is recognized through the presence of its genome in the polyploid. In this study, we aimed to determine the polyploid origin of Oxyria sinensis (2n = 40) for which only one congeneric species is known, that is diploid O. digyna (2n = 14). Genomic in situ hybridization (GISH), transcriptome, phylogenetic and demographic analyses, and ecological niche modelling were conducted for this purpose. GISH revealed that O. sinensis comprised 14 chromosomes from O. digyna and 26 chromosomes from an unknown ancestor. Transcriptome analysis indicated that following divergence from O. digyna, involving genome duplication around 12 million years ago (Ma), a second genome duplication occurred approximately 6 Ma to give rise to O. sinensis. Oxyria sinensis was shown to contain homologous gene sequences divergent from those present in O. digyna in addition to a set that clustered with those in O. digyna. Coalescent simulations indicated that O. sinensis expanded its distribution approximately 6–7 Ma, possibly following the second polyploidization event, whereas O. digyna expanded its range much later. It was also indicated that the distributions of both species contracted and re‐expanded during the Pleistocene climatic oscillations. Ecological niche modelling similarly suggested that both species experienced changes in their distributional ranges in response to Quaternary climatic changes. The extinction of the unknown ‘ghost’ tetraploid species implicated in the origin of O. sinensis could have resulted from superior adaptation of O. sinensis to repeated climatic changes in the region where it now occurs.
Hybridization between two cryptic filamentous brown seaweeds along the shore: analysing pre‐ and postzygotic barriers in populations of individuals with varying ploidy levels
Authors: Montecinos Alejandro E. , Guillemin Marie‐Laure , Couceiro Lucia , Peters Akira F. , Stoeckel Solenn , Valero Myriam
Published: March 2017

We aimed to study the importance of hybridization between two cryptic species of the genus Ectocarpus, a group of filamentous algae with haploid–diploid life cycles that include the principal genetic model organism for the brown algae. In haploid–diploid species, the genetic structure of the two phases of the life cycle can be analysed separately in natural populations. Such life cycles provide a unique opportunity to estimate the frequency of hybrid genotypes in diploid sporophytes and meiotic recombinant genotypes in haploid gametophytes allowing the effects of reproductive barriers preventing fertilization or preventing meiosis to be untangle. The level of hybridization between E. siliculosus and E. crouaniorum was quantified along the European coast. Clonal cultures (568 diploid, 336 haploid) isolated from field samples were genotyped using cytoplasmic and nuclear markers to estimate the frequency of hybrid genotypes in diploids and recombinant haploids. We identified admixed individuals using microsatellite loci, classical assignment methods and a newly developed Bayesian method (XPloidAssignment), which allows the analysis of populations that exhibit variations in ploidy level. Over all populations, the level of hybridization was estimated at 8.7%. Hybrids were exclusively observed in sympatric populations. More than 98% of hybrids were diploids (40% of which showed signs of aneuploidy) with a high frequency of rare alleles. The near absence of haploid recombinant hybrids demonstrates that the reproductive barriers are mostly postzygotic and suggests that abnormal chromosome segregation during meiosis following hybridization of species with different genome sizes could be a major cause of interspecific incompatibility in this system.
WHO 2016 classification: changes and advancements in the diagnosis of miscellaneous primary CNS tumours
Authors: Sahm F. , Reuss D. E. , Giannini C.
Published: March 2017

This short review highlights significant changes and recent findings incorporated to varying extent in the WHO 2016 definition of a variety of tumours, including peripheral nerve sheath tumours, meningiomas, mesenchymal nonmeningothelial tumours, melanocytic tumours, lymphomas and histiocytic tumours, germ cell tumours and non‐neuroendocrine pituitary tumours. Most notable classification changes include: adding ‘hybrid nerve sheath tumours’ to the spectrum of benign nerve sheath tumours; an updated definition of atypical meningioma (WHO grade II), including cases with brain invasion; recognizing dural solitary fibrous tumour (SFT) and haemangiopericytoma (HPC) as a single tumour entity characterized by NAB2 and STAT6 gene fusions for which the term SFT/HPC was chosen; recognizing that pituitary granular cell tumour, spindle cell oncocytoma, and pituicytoma all share nuclear expression of TTF‐1, possibly representing a spectrum of a single nosological entity derived from posterior pituitary glial cells. The most significant diagnostic markers which have emerged include: inactivation of NF1, CDKN2A, and PRC2 components, SUZ12 and EED in MPNST, leading to neurofibromin and H3K27me3 expression loss; GNAQ and GNA11 mutations in CNS primary melanocytic tumours; BRAFV600E mutation in histiocytic tumours (Langerhans cell histiocytosis and Erdheim‐Chester disease) and papillary craniopharyngioma, which provides both a diagnostic marker in the appropriate pathological setting and a therapeutic target. The WHO 2016 Classification has balanced cutting‐edge knowledge on the molecular characteristics of the miscellaneous CNS tumours reviewed here with a practical approach for their daily diagnostic work‐up. Much more progress can be expected in the classification of these neoplasms in the near future.