bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and esthetic outcome with immediate insertion and provisionalization with or without connective tissue grafting in presence of mucogingival recessions: A retrospective analysis with follow‐up between 1 and 8 years
Authors: Noelken Robert , Moergel Maximilian , Pausch Tobias , Kunkel Martin , Wagner Wilfried
Published: March 2018

Background

Recessions following immediate implant insertion are frequently reported in the literature. Data regarding implant installation in presence of mucogingival recessions are rare.

Purpose

This study observes soft tissue level changes following immediate implant insertion and provisionalization of implants with or without connective tissue grafts in the anterior maxilla in patients with initial mucogingival recession within a follow‐up period between one and eight years.

Materials and Methods

Twenty‐six patients with marginal gingival recessions, which were designated for extraction and immediate implant insertion in the anterior zone of the maxilla (13‐23), were included. Out of a larger group of immediate implants only single tooth replacements with 1 to 3 mm recession and a pre‐ and post‐op CB‐CT were selected. Facial bone deficiencies were grafted flaplessly with autologous bone in all sites. In a group of 13 patients the recessions (mean 2.3 ± 0.7 mm, range 1.0‐3.0 mm) were grafted additionally by connective tissue (ABG + CTG), in the remaining 13 patients no soft tissue grafting (mean recession 1.8 ± 0.6 mm, range 1.0‐3.0 mm) was performed (ABG). The marginal hard and soft tissue level, the width of the keratinized mucosa, the PES, and implant success were evaluated.

Results

After a mean follow‐up period of 45 months the recessions were significantly reduced in the ABG group from 1.8 to 0.9 mm. The improvement was even more pronounced in the ABG + CTG group (from 2.3 to 0.5 mm). The PES improved significantly in both groups. At final examination all implants were still in function. Within the observational period, in 5 of 13 implants a marginal bone loss of more than 1 mm was noticed in the ABG, but in none of the ABG + CTG group.

Conclusions

These clinical results provide evidence that immediate implant placement might improve the facial soft tissue level. This was more evident in cases with a greater recession and an additional treatment with connective tissue grafts.
Peri‐implant parameters, tumor necrosis factor‐alpha, and interleukin‐1 beta levels in vaping individuals
Authors: Al‐Aali Khulud A. , Alrabiah Mohammed , ArRejaie Aws S. , Abduljabbar Tariq , Vohra Fahim , Akram Zohaib
Published: March 2018

Background

To the author's knowledge, there has been no study that has assessed clinical, radiographic, and immunological peri‐implant parameters among individuals vaping e‐cigarette (e‐cig).

Purpose

This pilot study aimed to compare clinical and radiographic peri‐implant parameters and levels of tumor necrosis factor alpha (TNF‐α) and interleukin (IL)‐1β levels among individuals vaping e‐cigs and never smoker (NS).

Materials and Methods

Forty‐seven individuals vaping e‐cigs (group‐1) and 45 NS (group‐2) were included. Demographic and implant‐related data were collected using a structured baseline questionnaire. Peri‐implant plaque index (PI), bleeding on probing (BOP), and probing depth (PD) were recorded and peri‐implant bone loss (PIBL) were assessed using standardized digital radiographs. Enzyme‐linked immunosorbent assay was used to assess the levels of TNF‐α and IL‐1β in peri‐implant sulcular fluid.

Results

Bleeding on probing showed statistically significantly higher values in group‐2 patients as compared to group‐1 patients (P < .01). Probing depth ≥ 4 mm and PIBL was statistically significantly higher in group‐1 patients as compared to group‐2 patients (P < .05). Mean concentrations of TNF‐α (P < .001) and IL‐1β (P < .01) were statistically significantly increased in individuals in group 1 as compared with group 2. A significant positive correlations were found between TNF‐α levels and BOP (P = .024) and PIBL (P = .016); and significant positive correlation was found between IL‐1β and PIBL (P = .018) in group 1, respectively.

Conclusions

Clinical and radiographic peri‐implant parameters are compromised among vaping individuals. Increased levels of proinflammatory cytokines in peri‐implant sulcular fluid may suggest greater local inflammatory response in vaping individuals for peri‐implant inflammation.
Guided maxillary sinus floor elevation using deproteinized bovine bone versus graftless Schneiderian membrane elevation with simultaneous implant placement: Randomized clinical trial
Authors: Fouad Waleed , Osman Ahmed , Atef Mohammed , Hakam Maha
Published: March 2018

Objective

The aim of this study is to evaluate the analytical difference between the use of xenograft (control group) and graftless tenting (test group) technique after sinus lift procedure with simultaneous implant placement.

Materials and methods

Seventeen patients and 20 sinuses where operated for sinus lift procedures using lateral window approach with simultaneous implant placement. Deproteinized bovine bone (Xenograft) was used as a filling material in control group while nongrafted sinus lifting was performed in the test group. Multislice CT was obtained preoperatively and CBCT were obtained immediately postoperative and 6 months after operation. Osstell readings were taken at the time of implant placement and implant exposure (6 months)

Results

Mean bone height gain in the xenograft group was 8.59 ± 0.74 while that of the tenting group was 4.85 ± 0.5 and it was statistically significant (P < .05). Mean bone density values in the xenograft group was 375.59 ± 49.38 while that of the tenting group was 269.08 ± 16.27 and it was statistically significant (P < .05). Mean ISQ values for the xenograft group was 78.3 ± 5.08 while that of the tenting group was 74 ± 3.19 and it was statistically significant (P < .05).

Conclusions

Within the limitation of this study, sinus lift procedures with simultaneous implant placement using xenograft as a filling material or graftless technique are considered reliable procedures, however, the use of xenograft provide better results in all aspects regarding (bone height gain, bone density, and implant stability).
Long‐term outcome of surgical treatment of peri‐implantitis. A 2‐11‐year retrospective study
Authors: Berglundh Tord , Wennström Jan L. , Lindhe Jan
Published: March 2018

Objective

To assess long‐term clinical and radiological outcomes of surgical treatment of peri‐implantitis.

Material and methods

Files and radiographs from 50 patients who had received surgical treatment for peri‐implantitis were analyzed. Data on clinical characteristics prior to surgical therapy and at latest follow‐up were obtained. In each radiograph, the marginal bone level was assessed at the mesial and distal aspects of the affected implants. The treatment included oral hygiene instruction, professional supra‐mucosal instrumentation, and surgical therapy aiming at pocket elimination. Following flap elevation and removal of inflamed tissue, the affected implant was cleaned using gauze soaked in saline. Calculus was removed. When indicated, osseous re‐contouring was carried out to facilitate pocket elimination. Flaps were adjusted, sutured, and compressed to the crestal bone. Supportive therapy including oral hygiene control was provided with 4‐month intervals.

Results

Treatment was effective in resolving the inflammatory condition as documented by marked reduction in peri‐implant probing depth and bleeding on probing scores together with crestal bone level preservation. Treatment outcome was significantly better at implants with non‐modified surfaces than at implants with modified surfaces. The probability of an implant to exhibit no further bone loss or bone gain after treatment was high if the peri‐implant mucosa at the site presented with shallow pockets and the absence of bleeding on probing at follow‐up.

Conclusions

The results of the study revealed that (i) surgical treatment of peri‐implantitis was effective in the long‐term, (ii) outcome was better at implants with non‐modified than with modified surfaces, and (iii) preservation of crestal bone support was consistent with healthy peri‐implant tissue conditions.
Functional outcome and service engagement in major depressive disorder with psychotic features: comparisons with schizophrenia, schizoaffective disorder and bipolar disorder in a 6‐year follow‐up of the Cavan‐Monaghan First Episode Psychosis Study (CAMFEPS)
Authors: Kingston Tara , Scully Paul J. , Browne David J. , Baldwin Patrizia A. , Kinsella Anthony , O'Callaghan Eadbhard , Russell Vincent , Waddington John L.
Published: March 2018

Objective

While long‐term outcome following a first psychotic episode is well studied in schizophrenia (SZ), schizoaffective disorder (SA), and bipolar disorder (BD), major depressive disorder with psychotic features (MDDP) has received less investigation. This study compares MDDP with SZ, SA, and BD at 6‐year follow‐up.

Methods

At 6 years after a first psychotic episode, follow‐up data on psychopathology, functioning, quality of life, and service engagement were obtained for 27 cases of MDDP in comparison to 60 SZ, 27 SA, and 35 BD.

Results

Positive psychotic symptoms were less prominent in MDDP and BD than in SZ and SA. Negative symptoms, impaired functioning, and reduction in objectively determined quality of life were less prominent in MDDP and BD, intermediate in SA and most prominent in SZ. However, subjectively determined quality of life was indistinguishable across diagnoses. Service engagement was highest for MDDP, intermediate for SA and BD, and lowest for SZ.

Conclusions

At 6‐year follow‐up, these diagnoses are characterized by quantitative rather than qualitative differences in psychopathology, functionality, quality of life, and service engagement, with considerable overlap between them. These findings suggest that MDDP should join SZ, SA, and BD in a milieu of psychosis that transcends arbitrary boundaries.
Hearing aids in patients with vestibular schwannoma: Interest of the auditory brainstem responses
Authors: Reffet K. , Lescanne E. , Bobillier C. , Aussedat C. , Bakhos D.
Published: March 2018

Objective

Hearing loss subsequent to a unilateral vestibular schwannoma (VS) has an impact on the social life of non‐operated patients. We investigated the utility of auditory brainstem responses (ABRs) for predicting the results of auditory rehabilitation in such patients.

Design

Prospective study.

Setting

University tertiary medical centre.

Participants

We collected the demographic, audiometric, ABR and imaging data of non‐operated patients with unilateral VS. A hearing aid trial was performed over 1 month. We assessed auditory performance following the auditory rehabilitation according to the ABR results. Patients with distinct waves (I, III and V) were included in the “distinct ABR” group and patients with no ABR were included in the “desynchronised ABR” group. Main outcome measures: Following the trial, audiometric performance and quality of life were evaluated with the Glasgow Benefit Inventory (GBI).

Subjects and Method

We collected the demographic, audiometric, ABR and imaging data of non‐operated patients with unilateral VS. A hearing aid trial was performed over 1 month. Following the trial, audiometric performance and quality of life were evaluated with the Glasgow Benefit Inventory (GBI). We assessed auditory performance following the auditory rehabilitation according to the ABR results. Patients with distinct waves (I, III and V) were included in the “distinct ABR” group and patients with no ABR were included in the “desynchronised ABR” group.

Results

In total, 25 patients were included in this prospective study; 15 in the “distinct ABR” group and 10 in the “desynchronised ABR” group. The speech recognition threshold (SRT, P < .0001; W = −120) and speech discrimination score (P = .0005; W = 78) were significantly improved in the aided vs unaided conditions. These improvements were not observed in the “desynchronised ABR” group for the SRT (P = .48; W = −10) and word recognition score (P = .06; W = 15). Ninety‐three per cent of the patients in the “distinct ABR” group kept significantly (P = .04) the hearing aids following the trial compared to 20% in the “desynchronised ABR” group.

Conclusions

Auditory brainstem responses can help to predict the auditory performance following auditory rehabilitation in unilateral non‐operated VS patients.
C‐reactive protein is an independent prognostic marker in patients with tongue carcinoma ‐ A retrospective study
Authors: Graupp M. , Schaffer K. , Wolf A. , Vasicek S. , Weiland T. , Pondorfer P. , Holzmeister C. , Moser U. , Thurnher D.
Published: March 2018

Objectives

Reliable prognostic markers are lacking for tongue carcinoma. C‐reactive protein (CRP) and a ratio from neutrophils/lymphocytes (NLR) are biomarkers, associated with prognosis in solid cancers. Aim of this work was to investigate the role of CRP and NLR in prognosis of patients with tongue carcinoma.

Design

Retrospective cohort study.

Setting

We retrospectively analysed data of patients treated for tongue carcinoma at our institution. Levels of CRP, Neutrophils and Lymphocytes were measured pretherapeutic.

Participants

197 patients treated for squamous cell carcinoma of the tongue between 2002 and 2015.

Main outcome measures

Overall survival, disease‐free survival.

Results

Elevated CRP was significantly associated with shorter overall survival in our cohort in uni‐ and multivariate analysis. NLR was not associated with prognosis.

Conclusion

In the present study we could confirm the role of CRP as an independent prognostic marker in patients with tongue carcinoma. Incorporating this marker in prognostication could represent a valuable and moreover inexpensive tool for improved decisions making concerning therapy in the future.
Reliable sonographic features for nodal thyroglobulin to diagnose recurrent lymph node metastasis from papillary thyroid carcinoma
Authors: Jiang H.‐J. , Wu C.‐W. , Chiang F.‐Y. , Chiou H.‐Y.C. , Chen I.‐J. , Hsiao P.‐J.
Published: March 2018

Objectives

Ultrasound‐guided aspiration cytology (US‐FNAC) was previously used to diagnose lymph node metastasis of papillary thyroid carcinoma (PTC). Combined US‐FNAC with nodal thyroglobulin (LN‐FNA‐Tg) significantly improved the diagnostic rate. However, diagnostic accuracy depends on proper node selection. Therefore, it is crucial to choose the nodes with reliable sonographic features to guide clinician for confirmation.

Design and Setting

Retrospective cohort study was carried out in one medical centre from 2011 to 2014.

Participants

A total of 148 patients with PTC, being treated by total thyroidectomy and radioiodine, were assessed for potential nodal metastases by ultrasound.

Main outcome measures

Lymph nodes with cystic content, peripheral hypervascularity, calcification, hyperechoic content, the absence of hilum and Solbiati index < 2 indicated risk of malignancy. US‐FNAC and LN‐FNA‐Tg were both performed. Positive nodal metastasis was further confirmed by dissection. Risk impact of these sonographic features on LN‐FNA‐Tg to diagnose nodal metastasis was tested by logistic regression analysis based on the significance in both univariate and multivariate models.

Results

Overall, 49 lymph nodes were documented as recurrent nodal metastasis. LN‐FNA‐Tg greater than serum thyroglobulin and higher than 1 ng/mL achieved 100% of diagnostic rate for recurrent nodal metastasis. The malignant sonographic features that significantly cohered with positive LN‐FNA‐Tg were cystic and hyperechoic content and lack hilum, in sequence.

Conclusions

LN‐FNA‐Tg is an excellent tool to quantitatively diagnose nodal metastasis. To achieve ideal diagnosis, the most reliable sonographic features were cystic content, hyperechoic content and the absence of hilum in lymph nodes, but not calcification or Solbiati index < 2.
High sensitivity and negative predictive value of sentinel lymph node biopsy in a retrospective early stage oral cavity cancer cohort in the Northern Netherlands
Authors: Boeve K. , Schepman K.P. , Schuuring E. , Roodenburg J.L.N. , Halmos G.B. , van Dijk B.A.C. , Boorsma R.A.C. , de Visscher J.G.A.M. , Brouwers A.H. , van der Vegt B. , Witjes M.J.H.
Published: March 2018

Objectives

In cT1‐2N0, oral squamous cell carcinoma (OSCC) occult metastases are detected in 23%‐37% of cases. Sentinel lymph node biopsy (SLNB) was introduced in head and neck cancer as a minimally invasive alternative for an elective neck dissection in neck staging. Meta‐analyses of SLNB accuracy show heterogeneity in the existing studies for reference standards, imaging techniques and pathological examination. The aim of this study was to assess the sensitivity and negative predictive value (NPV) of the SLNB in detecting occult metastases in cT1‐2N0 OSCC in a well‐defined cohort.

Design

Retrospective study. The SLNB procedure consisted of lymphoscintigraphy, SPECT/CT‐scanning and gamma probe detection. Routine follow‐up was the reference standard for the SLNB negative neck. Histopathological examination of sentinel lymph nodes (SLN) consisted of step serial sectioning, haematoxylin‐eosin and cytokeratin AE1/3 staining.

Setting

Two comprehensive oncology centres.

Participants

A total of 91 consecutive patients with primary cT1‐2N0 OSCC treated by primary resection and neck staging by SLNB procedure between 2008 and 2016.

Main outcome measures

Sensitivity and negative predictive value.

Results

In all cases, SLNs were harvested. A total of 25 (27%) patients had tumour‐positive SLNs. The median follow‐up was 32 months (range 2‐104). Four patients were diagnosed with an isolated regional recurrence in the SLNB negative neck side resulting in an 85% sensitivity and a 94% NPV.

Conclusion

In our cohort, the SLNB detected occult metastases in early OSCC with 85% sensitivity and 94% NPV. This supports that SLNB is a reliable procedure for surgical staging of the neck in case of oral cT1‐2N0 SCC.
Stable pneumorectum using an inline glove – a cost‐effective technique to facilitate transanal total mesorectal excision
Authors: Loong T. H. , Liu H. M. , Fong S. S.
Published: March 2018

Aim

Transanal total mesorectal excision (taTME) is a novel approach for resection of the rectum. Use of a standard insufflator to create pneumorectum, however, results in bellowing–large heaving motions from insufflation of air that can frustrate surgery. We report the successful application of our technique, stable pneumorectum using an inline glove (SPRING), for the performance of transanal rectal excision in a series of 17 patients using a standard laparoscopic insufflator.

Method

A retrospective review of 17 patients using the SPRING technique was performed between October 2015 and October 2016. Characteristics of these patients were evaluated, and technique‐related short‐term outcome was reviewed.

Results

The SPRING technique was successfully used in patients who underwent both minimally invasive (n = 14) and open (n = 3) approaches in the abdominal stage of the surgery. In the 12 patients who had rectal cancer for whom SPRING was used to facilitate taTME there were no conversions to an alternative access for rectal resection, the median duration of the TME part of the operation was 95 min (62–147) and there was one R1 resection (8%). Billowing was not a significant problem in any of the 17 patients during the surgery.

Conclusion

In this case series we have successfully shown the feasibility of the SPRING technique as a practical and cost‐effective solution to the problem of billowing during taTME.
Unified forms of the CDR method of approximate reasoning on Antanassov's intuitionistic fuzzy sets and its property analysis
Authors: Li Jun , Xu Xiaofu
Published: March 2018

Two basic models of fuzzy reasoning are fuzzy modus ponens and fuzzy modus tollens. Correspondingly, the key point of intuitionistic fuzzy reasoning is to solve the problems of intuitionistic fuzzy modus ponens (IFMP) and intuitionistic fuzzy modus tollens (IFMT). In many important algorithms of fuzzy reasoning, the Consequent Dilation Rule (CDR) method possesses the virtue of unconditional reductivity. This paper proposed an intuitionistic CDR (ICDR) method for IFMP and IFMT problems by extending the CDR method to the intuitionistic fuzzy reasoning. It was proved that the intuitionistic CDR methods, both for IFMP and IFMT, are unconditionally reductive in the circumstance of using residual intuitionistic implication operators. At the same time, the continuity, approximation properties and robustness of the CDR method in Łukasiewicz intuitionistic fuzzy reasoning space have been studied by using the new defined average natural distance between intuitionistic fuzzy sets.
Complementary‐based coalition formation for energy microgrids
Authors: Yasir Muhammad , Purvis Martin , Purvis Maryam , Savarimuthu Bastin Tony Roy
Published: March 2018

In recent years, the notion of electrical energy microgrids (MGs), in which communities share their locally generated power, has gained increasing interest. Typically, the energy generated comes from renewable resources, which means that its availability is variable, ie, sometimes there may be energy surpluses and at other times energy deficits. This energy variability can be ameliorated by trading energy with a connected electricity grid. However, since main electricity grids are subject to faults or other outages, it can be advantageous for energy MGs to form coalitions and share their energy among themselves. In this work, we present our model for the dynamic formation of such MG coalitions. In our model, MGs form coalitions on the basis of complementary weather patterns. Our agent‐based model, which is scalable and affords autonomy among the MGs participating in the coalition (agents can join and depart from coalitions at any time), features methods to reduce overall “discomfort” so that, even when all participating MGs in a coalition experience deficits, they can share energy so that their overall discomfort is reduced. We demonstrate the efficacy of our model by showing empirical studies conducted with real energy production and consumption data.
Progression and new onset of nonalcoholic fatty liver disease in living kidney donors compared to healthy controls
Authors: Katchman Helena , Zelber‐Sagi Shira , Baruch Roni , Berman Galia , Schwartz Idit F. , Schwartz Doron , Nakache Richard , Goykhman Yaacov , Katz Polina , Shibolet Oren , Shashar Moshe , Grupper Ayelet
Published: March 2018

Background

There is growing evidence linking nonalcoholic fatty liver disease (NAFLD) with reduced glomerular filtration rate (GFR). Living kidney donors do not have underlying kidney disease, but have reduced GFR as a result of nephrectomy. Whether kidney donation is associated with a higher risk for development or progression of NAFLD is currently unknown.

Methods

Retrospective evaluation of metabolic parameters and sonographic evidence of NAFLD were performed in 232 living kidney donors and 162 healthy controls.

Results

A total of 25 donors and 44 controls had NAFLD at baseline. During a mean follow‐up of 6.8 years, 6 donors (24%) and 17 controls (38.6%) (P = .29) had a remission of NAFLD, related with decreased body mass index (BMI). The progression of NAFLD fibrosis score was similar in both groups. New onset of NAFLD was observed in 14 (6.8%) donors and 13 (11.01%) controls (P = .211), and was related to increased BMI and a higher baseline Fatty Liver Index score. Neither eGFR nor urine albumin excretion in the donors were related to new onset or progression of NAFLD.

Conclusions

Reduced kidney function secondary to kidney donation is not associated with increased incidence or progression of NAFLD.
University of Wisconsin vs normal saline solutions for preservation of blood vessels of brain dead donors: A histopathological study
Authors: Kazemi Kourosh , Nikeghbalian Zahra , Yaghmaei Shekoofeh , Nikeghbalian Saman , Shamsaeifar Alireza , Asgharnia Yasaman , Dehghankhalili Maryam , Golchini Alireza , Malekhosseini Seyed Ali
Published: March 2018

Objective

To compare the cellular changes of harvested arteries which were preserved in normal saline (NS) and the standard and routinely used University of Wisconsin (UW) solution.

Methods

This experimental study was conducted on 20 brain dead patients. The femoral and iliac arteries were bilaterally removed and were placed in NS and UW solutions. The vascular change indices including endothelial detachment (ED), medial detachment (MD), and internal elastic membrane disruption (IEMD) were surveyed for each preserver in the first, 5th, 10th, and 21st day.

Results

The mean age of the included patients was 32.28 ± 8.88 years, and there were 13 (65.0%) men and 7 (35.0%) women among the patients. The NS and UW preservation solutions were comparable regarding the indices of vascular changes at first, 5th, and 10th day of the study. Only in 21st day of the study, there was a significant difference between 2 group regarding MD changes (P = .049).

Conclusion

The results of this in vitro study demonstrated that NS can be used as a worthy preserver for harvested vessels for up to 21 days, especially in resource‐limited transplantation centers.
Electrocardiographic changes before and after successful kidney transplantation and associations with cardiovascular and mortality outcomes
Authors: Paajanen Hanna , Helanterä Ilkka , Kaartinen Kati , Nikus Kjell , Eskola Markku , Groop Per‐Henrik , Koskinen Petri
Published: March 2018

Introduction

Electrocardiographic (ECG) changes before and after kidney transplantation are not well‐defined. Our aim was to describe the evolution of ECG in patients on dialysis before and after successful kidney transplantation and to explore the association between ECG findings and major cardiovascular (CV) events and mortality after kidney transplantation.

Patients and methods

Electrocardiographics were collected retrospectively 3 times: at entry to the transplantation waiting list, at transplantation, and 1 year after the transplantation from 212 kidney transplantation recipients. Altogether 19 ECG variables were analyzed.

Results

Left ventricular hypertrophy was present in 10.2% by the Cornell voltage‐duration product criteria and 10.7% by the Sokolow‐Lyon voltage criteria before kidney transplantation. The presence of ST depression (OR 3.12, 95% CI 1.12 −8.7 and P = .03) at entry to the waiting list and Q wave at the time of transplantation (OR 3.28, 95% CI 1.06‐10.10 and P = .04) were both independently associated with major CV events after the transplantation. In addition, the presence of Q wave at entry to the waiting list was a risk factor of premature death after the transplantation (OR 2.92, 95% CI 1.06‐8.05 and P = .04).

Discussion

Careful analysis of the ECG before transplantation can be used to estimate cardiovascular events and mortality risk after kidney transplantation.
Association Between Serotonin Syndrome and Second‐Generation Antipsychotics via Pharmacological Target‐Adverse Event Analysis
Authors: Racz Rebecca , Soldatos Theodoros G. , Jackson David , Burkhart Keith
Published: March 2018

Case reports suggest an association between second‐generation antipsychotics (SGAs) and serotonin syndrome (SS). The US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) was analyzed to generate hypotheses about how SGAs may interact with pharmacological targets associated with SS. FAERS was integrated with additional sources to link information about adverse events with drugs and targets. Using Proportional Reporting Ratios, we identified signals that were further investigated with the literature to evaluate mechanistic hypotheses formed from the integrated FAERS data. Analysis revealed common pharmacological targets perturbed in both SGA and SS cases, indicating that SGAs may induce SS. The literature also supported 5‐HT2A antagonism and 5‐HT1A agonism as common mechanisms that may explain the SGA‐SS association. Additionally, integrated FAERS data mining and case studies suggest that interactions between SGAs and other serotonergic agents may increase the risk for SS. Computational analysis can provide additional insights into the mechanisms underlying the relationship between SGAs and SS.
Assessment of Relative Bioavailability of Moroctocog Alfa and Moroctocog Alfa (AF‐CC) in Subjects With Severe Hemophilia A
Authors: Korth‐Bradley Joan , Rupon Jeremy , Plotka Anna , Charnigo Robert , Rendo Pablo
Published: March 2018

An open‐label, single‐dose, randomized, two‐period, crossover study comparing the pharmacokinetics of factor VIII activity in plasma (FVIII:C) after administration of an albumin‐free presentation of moroctocog alfa (test) and moroctocog alfa manufactured using the previous technique (reference) was conducted in 30 (25 evaluable) male subjects who had severe hemophilia A (FVIII:C < 1 IU/dL). Blood samples were collected for 48 h after administration of each dose. FVIII:C was assayed using a chromogenic substrate assay. The FVIII:C pharmacokinetic parameters were calculated using noncompartmental analysis. The presentations would be bioequivalent if the 90% confidence limits of the ratio of the geometric mean values of AUCinf and recovery fell within the interval of 80–125%. The bioequivalence criteria were met. A total of 10 treatment‐related adverse events were observed in a total of nine subjects. All were mild and none was determined to be related to administration of study medication.
Fatty Acid Amide Hydrolase Inhibition by JNJ‐42165279: A Multiple‐Ascending Dose and a Positron Emission Tomography Study in Healthy Volunteers
Authors: Postnov Andrey , Schmidt Mark E. , Pemberton Darrel J. , de Hoon Jan , van Hecken Anne , van den Boer Maarten , Zannikos Peter , van der Ark Peter , Palmer James A. , Rassnick Stef , Celen Sofie , Bormans Guy , van Laere Koen
Published: March 2018

Inhibition of fatty acid amide hydrolase (FAAH) potentiates endocannabinoid activity and is hypothesized to have therapeutic potential for mood and anxiety disorders and pain. The clinical profile of JNJ‐42165279, an oral selective FAAH inhibitor, was assessed by investigating the pharmacokinetics, pharmacodynamics, safety, and binding to FAAH in the brain of healthy human volunteers. Concentrations of JNJ‐42165279 (plasma, cerebrospinal fluid (CSF), urine) and fatty acid amides (FAA; plasma, CSF), and FAAH activity in leukocytes was determined in a phase I multiple ascending dose study. A positron emission tomography study with the FAAH tracer [11C]MK3168 was conducted to determine brain FAAH occupancy after single and multiple doses of JNJ‐42165279. JNJ‐42165279 administration resulted in an increase in plasma and CSF FAA. Significant blocking of brain FAAH binding of [11C]MK3168 was observed after pretreatment with JNJ‐42165279. JNJ‐42165279 produces potent central and peripheral FAAH inhibition. Saturation of brain FAAH occupancy occurred with doses ≥10 mg of JNJ‐42165279. No safety concerns were identified.
Novel Application of the Two‐Period Microtracer Approach to Determine Absolute Oral Bioavailability and Fraction Absorbed of Ertugliflozin
Authors: Raje Sangeeta , Callegari Ernesto , Sahasrabudhe Vaishali , Vaz Alfin , Shi Haihong , Fluhler Eric , Woolf Eric J. , Schildknegt Klaas , Matschke Kyle , Alvey Christine , Zhou Susan , Papadopoulos Dimitris , Fountaine Robert , Saur Didier , Terra Steven G. , Stevens Lloyd , Gaunt Daniel , Cutler David L.
Published: March 2018

Ertugliflozin, a sodium glucose cotransporter‐2 inhibitor, is approved in the United States for treatment of type 2 diabetes mellitus. A novel two‐period study design with 14C microtracer dosing in each period was used to determine absolute oral bioavailability (F) and fraction absorbed (Fa) of ertugliflozin. Eight healthy adult men received 100‐μg i.v. 14C‐ertugliflozin (400 nCi) dose 1 h after a 15‐mg oral unlabeled ertugliflozin dose (period 1), followed by 100 μg 14C‐ertugliflozin orally along with 15 mg oral unlabeled ertugliflozin (period 2). Unlabeled ertugliflozin plasma concentrations were determined using high‐performance liquid‐chromatography tandem mass spectrometry (HPLC‐MS/MS). 14C‐ertugliflozin plasma concentrations were determined using HPLC‐accelerator mass spectrometry (AMS) and 14C urine concentrations were determined using AMS. F ((area under the curve (AUC)p.o./14C‐AUCi.v.)*(14C‐Dosei.v./Dosep.o.)) and Fa ((14C_Total_Urinep.o./14C_Total_Urinei.v.)* (14C‐Dosei.v./14C‐Dosep.o.)) were estimated. Estimates of F and Fa were 105% and 111%, respectively. Oral absorption of ertugliflozin was complete under fasted conditions and F was ∼100%. Ertugliflozin was well tolerated.
Synchronous mantle cell lymphoma and lung adenocarcinoma presenting in a pleural effusion: A rare tumour combination and a potential pitfall of cytodiagnosis
Authors: Kai K. , Ryu Y. , Kamochi K. , Nishioka A. , Kubota Y. , Nakamura M. , Kimura S. , Sueoka E. , Aishima S.
Published: March 2018

This report describes the first case of mantle cell lymphoma synchronously appearing with lung adenocarcinoma in pleural effusion. MCL cells were not detected initially due to the presence of an overwhelming number of adenocarcinoma cell clusters.
Presence of koilocytosis in low‐grade smears of high‐risk HPV‐positive women is a negative predictor for cervical intraepithelial neoplasia grade 3 or more
Authors: Siebers A. G. , van der Linden H. , Vedder J. E. M. , Bekkers R. L. M. , Melchers W. L. G. , Bulten J.
Published: March 2018

Objective

The Netherlands converted to high‐risk (hr)HPV‐based screening in 2017. An increase in referral of hrHPV‐positive women with low risk for cervical intraepithelial neoplasia grade 3 or more (CIN3+) is anticipated and reduction of unjustified referrals will have priority. The relevance of koilocytosis in relation to the underlying risk of high‐grade CIN in a primary HPV screening setting is unclear. The aim was to investigate whether the risk for CIN3+ differs between hrHPV‐positive atypical squamous cells of undetermined significance (ASC‐US)/low‐grade squamous intraepithelial lesion (LSIL) with or without koilocytosis.

Methods

Retrospective cohort study, using data from the Dutch national pathology database (PALGA). The population was 1201 hrHPV‐positive women with cytological diagnosis of ASC‐US/LSIL. Reporting of koilocytosis was assessed as well as detection rates of CIN1 or less, CIN2 and CIN3+ for ASC‐US/LSIL cytology stratified by presence or absence of koilocytosis. Crude and adjusted odds ratios were determined.

Results

Koilocytosis was present in 40.1% of ASC‐US and 45.9% of LSIL cases. CIN3+ is significantly less often found when koilocytosis is present (7.8% for hrHPV‐positive ASC‐US with‐ vs 15.8% without koilocytosis). For hrHPV‐positive LSIL this was 11.7% vs 20.2%. The crude and adjusted odds ratios for CIN3+ was 0.45 for hrHPV‐positive ASC‐US and 0.52 for hrHPV‐positive LSIL.

Conclusions

The presence of koilocytosis is a negative predictor of CIN3+. The risk of hrHPV‐positive ASC‐US with koilocytosis is in the same range as hrHPV‐positive/cytology negative cases and in a setting of primary hrHPV screening these cases could be followed conservatively by repeat cytology. The results should be confirmed by the first data from the Dutch HPV‐based screening programme.
Urinary cytology and the Paris system for reporting urinary cytology: Implications for urological management
Authors: Gupta M. , VandenBussche C. J. , Bivalacqua T. J.
Published: March 2018

By reducing the rate of indeterminate (atypical) diagnoses and standardising reporting terminology, The Paris System for Reporting Urine Cytology helps focus the application of cytology towards the detection primarily of high‐grade urothelial carcinoma. We present a urology‐based perspective of how the new system has influenced clinical decision‐making.
Interactions among stressors may be weak: Implications for management of freshwater macroinvertebrate communities
Authors: Kath Jarrod , Thomson James R. , Thompson Ross M. , Kefford Ben J. , Dyer Fiona J. , Mac Nally Ralph
Published: March 2018

Aim

Ecological models that do not account for interactions among stressors, if interactions are important, could be inaccurate and lead to inefficient conservation strategies. Conversely, if interactions are not important (i.e., stressors operate largely independently), then actions concentrating on a stressor‐by‐stressor basis would be warranted. Here, we investigated whether interactions among multiple stressors affected widely used indices of freshwater macroinvertebrate biodiversity, which are sensitive to environmental change at management‐relevant scales (i.e., reaches and catchments).

Location

State of Victoria, south‐eastern Australia.

Methods

We used a 7,418‐sample dataset for stream macroinvertebrates from 2,165 sites distributed over 237,630 km2 for 20 years. We calculated the interactive effects on stream macroinvertebrates of stressors operating at different scales, namely vegetation loss at the catchment and reach scales and hydrological change and salinization at the local scale. The importance of interactions among multiple stressors was assessed by comparing the cross‐validated predictive performance of models with and without multiple stressor interaction terms.

Results

Cross‐validated models explained 31%–63% of the variation in the macroinvertebrate responses. The most important stressors were catchment vegetation loss (the proportion of remaining native vegetation cover) and salinity. The inclusion of interaction terms did not increase cross‐validated predictive performance, which indicates that there was little evidence that interactions among stressors were important for explaining variation in commonly used freshwater macroinvertebrate condition indices.

Main conclusions

Interactions among vegetation, salinity and hydrological change stressors may not always be of importance for determining patterns of stream macroinvertebrate biodiversity, so that such interactions may not necessarily be critical considerations for catchment and reach scale management, at least if based on these or comparable condition indices. The mitigation of the impacts of vegetation loss, salinization and hydrological change stressors one‐by‐one probably is sufficient to guide conservation activities and might be advantageous if socio‐political contexts make it difficult to address interactions among stressors.
Are all data types and connectivity models created equal? Validating common connectivity approaches with dispersal data
Authors: Zeller Katherine A. , Jennings Megan K. , Vickers T. Winston , Ernest Holly B. , Cushman Samuel A. , Boyce Walter M.
Published: March 2018

Aim

There is enormous interest in applying connectivity modelling to resistance surfaces for identifying corridors for conservation action. However, the multiple analytical approaches used to estimate resistance surfaces and predict connectivity across resistance surfaces have not been rigorously compared, and it is unclear what methods provide the best inferences about population connectivity. Using a large empirical data set on puma (Puma concolor), we are the first to compare several of the most common approaches for estimating resistance and modelling connectivity and validate them with dispersal data.

Location

Southern California, USA.

Methods

We estimate resistance using presence‐only data, GPS telemetry data from puma home ranges and genetic data using a variety of analytical methods. We model connectivity with cost distance and circuit theory algorithms. We then measure the ability of each data type and connectivity algorithm to capture GPS telemetry points of dispersing pumas.

Results

We found that resource selection functions based on GPS telemetry points and paths outperformed species distribution models when applied using cost distance connectivity algorithms. Point and path selection functions were not statistically different in their performance, but point selection functions were more sensitive to the transformation used to convert relative probability of use to resistance. Point and path selection functions and landscape genetics outperformed other methods when applied with cost distance; no methods outperformed one another with circuit theory.

Main conclusions

We conclude that path or point selection functions, or landscape genetic models, should be used to estimate landscape resistance for wildlife. In cases where resource limitations prohibit the collection of GPS collar or genetic data, our results suggest that species distribution models, while weaker, may still be sufficient for resistance estimation. We recommend the use of cost distance‐based approaches, such as least‐cost corridors and resistant kernels, for estimating connectivity and identifying functional corridors for terrestrial wildlife.
Combined exposure to hydroelectric expansion, climate change and forest loss jeopardies amphibians in the Brazilian Amazon
Authors: Silva Yuri B. da Silva e , Ribeiro Bruno R. , Thiesen Brum Fernanda , Soares‐Filho Britaldo , Loyola Rafael , Michalski Fernanda
Published: March 2018

Aim

Human‐driven impacts constantly threat amphibians, even in largely protected regions such as the Amazon. The Brazilian Amazon is home to a great diversity of amphibians, several of them currently threatened with extinction. We investigated how climate change, deforestation and establishment of hydroelectric dams could affect the geographic distribution of Amazonian amphibians by 2030 and midcentury.

Location

The Brazilian Amazon.

Methods

We overlapped the geographic distribution of 255 species with the location of hydroelectric dams, models of deforestation and climate change scenarios for the future.

Results

We found that nearly 67% of all species and 54% of species with high degree of endemism within the Legal Brazilian Amazon would lose habitats due to the hydroelectric overlapping. In addition, deforestation is also a potential threat to amphibians, but had a smaller impact compared to the likely changes in climate. The largest potential range loss would be caused by the likely increase in temperature. We found that five amphibian families would have at least half of the species with over 50% of potential distribution range within the Legal Brazilian Amazon limits threatened by climate change between 2030 and 2050.

Main conclusions

Amphibians in the Amazon are highly vulnerable to climate change, which may cause, directly or indirectly, deleterious biological changes for the group. Under modelled scenarios, the Brazilian Government needs to plan for the development of the Amazon prioritizing landscape changes of low environmental impact and economic development to ensure that such changes do not cause major impacts on amphibian species while reducing the emission of greenhouse gases.
Outcomes after endoscopic ultrasound‐guided ethanol‐lipiodol ablation of small pancreatic neuroendocrine tumors
Authors: Choi Jun‐Ho , Park Do Hyun , Kim Myung‐Hwan , Hwang Hee Sang , Hong Seung‐Mo , Song Tae Jun , Lee Sang Soo , Seo Dong‐Wan , Lee Sung Koo
Published: March 2018

Background and Aim

Little is known about the standard care of small (<2 cm in diameter) pancreatic neuroendocrine tumors (PNET). The aim of the present study was to determine the clinical outcomes of small PNET after endoscopic ultrasound (EUS)‐guided ethanol‐lipiodol ablation (EUS‐ELA).

Methods

In this prospective cohort study, consecutive patients who underwent EUS‐ELA for PNET were enrolled and were followed for ≥3 years. Treatment efficacy was the primary outcome measure.

Results

In total, 33 patients who had 40 pathologically confirmed PNET (<2 cm in diameter) were enrolled for final analysis. A total of 63 EUS‐ELA sessions were successfully carried out (mean, 1.9 sessions per patient, 1.6 sessions per tumor), which included 40 initial sessions and 23 repeated sessions owing to incomplete ablation. Median actual volume of ethanol‐lipiodol mixture injected per session was 1.1 mL (IQR 0.8–1.9 mL). Complete ablation was achieved in 24 of 40 tumors (60%) with one (18 tumors, 45%) or two (24 tumors, 60%) sessions of EUS‐ELA. Lipiodol retention within tumor had better treatment outcomes (P = 0.004). Rate of procedure‐related adverse events was 3.2%. No malignancy or lymph node metastasis was discovered during a median follow up of 42 months (IQR 39–46 months).

Conclusions

We found that EUS‐ELA was a safe and effective alternative option in the management of PNET <2.0 cm in diameter; 60% of patients achieved complete ablation. Lipiodol retention within tumor may be a useful early predictor of treatment effectiveness. Trial registered at ClinicalTrials.gov (NCT 01902238).
Progress in the genetics of autism spectrum disorder
Authors: Woodbury‐Smith Marc , Scherer Stephen W
Published: March 2018

A genetic basis for autism spectrum disorder (ASD) is now well established, and with the availability of high‐throughput microarray and sequencing platforms, major advances have been made in our understanding of genetic risk factors. Rare, often de novo, copy number and single nucleotide variants are both implicated, with many ASD‐implicated genes showing pleiotropy and variable penetrance. Additionally, common variants are also known to play a role in ASD's genetic etiology. These new insights into the architecture of ASD's genetic etiology offer opportunities for the identification of molecular targets for novel interventions, and provide new insight for families seeking genetic counselling.

What the paper adds

A number of rare genetic variants are implicated in autism spectrum disorder (ASD), with some showing recurrence.

Common genetic variants are also important and a number of loci are now being uncovered.

Genetic testing for individuals with ASD offers the opportunity to identify relevant genetic etiology.
The Gait Outcomes Assessment List (GOAL): validation of a new assessment of gait function for children with cerebral palsy
Authors: Thomason Pam , Tan Annie , Donnan Alice , Rodda Jill , Graham H Kerr , Narayanan Unni
Published: March 2018

Aim

We investigated the validity of the Gait Outcomes Assessment List (GOAL), as an assessment of gait function in children with cerebral palsy (CP).

Method

We studied a prospective cohort of 105 children with CP (Gross Motor Function Classification System [GMFCS] levels I–III; 65 males, 40 females; mean [SD] age 11y 11mo [3y 5mo], range 6–20y), who attended gait assessment over a 10‐month period. Parents completed the GOAL, Functional Mobility Scale (FMS), and Functional Assessment Questionnaire (FAQ) during their child's gait evaluation. Ninety children completed instrumented gait analysis (IGA). Total GOAL and domain scores, Gait Profile Score (GPS), and Gait Variable Scores were calculated.

Results

The total GOAL discriminated between GMFCS levels (mean [SD] GMFCS level I, 72.5 [12.7]; GMFCS level II, 61.4 [13.0]; GMFCS level III, 38.8 [10.6]; [F2,97=42.4, p<0.001]). Moderate correlations were found between total GOAL and FMS (5m and 50m r=0.59; 500m r=0.66) and FAQ walking (r=0.77) and activities list (r=0.75, p<0.01). There was a moderate negative correlation between total GOAL and GPS (r=−0.59) and gait appearance domain and GPS (r=−0.52, p<0.01).

Interpretation

The GOAL is a valid assessment of gait function in ambulant children with CP. It has the potential to improve understanding of the child's and parents’ priorities and thus, in conjunction with IGA, provide a more balanced assessment across the domains of the World Health Organization's International Classification of Functioning, Disability and Health.

What this paper adds

The Gait Outcomes Assessment List (GOAL) can discriminate between Gross Motor Function Classification System levels.

The GOAL correlates with standard functional assessments and gait analysis.

Used with gait analysis, the GOAL provides comprehensive assessment across all International Classification of Functioning, Disability and Health domains.