bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi‐Objective Genetic Algorithm Assisted by an Artificial Neural Network Metamodel for Shape Optimization of a Centrifugal Blood Pump
Authors: Ghadimi Behnam , Nejat Amir , Nourbakhsh Seyed Ahmad , Naderi Nasim
Published: October 2018

A centrifugal blood pump is a common type of the pump used as a left ventricular assist device (LVAD) in the medical industries. The reduction of the LVADs hemolysis level to reduce the blood damage is one of the major concerns in designing of such devices. Also, the enhancement of the LVADs efficiency to decrease the battery size is another design requirement. The blood damage critically depends on the state of the blood being pumped. Besides the blood state, the blood damage also depends on the pump impeller and volute geometries. In this research, a multi‐objective optimization of a centrifugal blood pump is performed. A complete 3D‐optimization platform is established for both impeller and volute of a centrifugal blood pump consisting of parametric modeling, automatic mesh generation, computational fluid dynamics (CFD) simulation, and optimization strategy. A vast number of cases with various impeller and volute shapes are numerically simulated. Three different metamodels are created using artificial neural networks (ANNs) in order to approximate the pump hydraulic efficiency, hemolysis index (HI), and pressure head. The inverse of the relative pressure head is defined as the first objective and the summation of relative hemolysis index and the inverse of the relative efficiency is assumed as the second objective. Non‐dominated Sorting Genetic Algorithm‐II (NSGA‐II) is used to find the Pareto Front. A set of optimal points is selected. Finally, for the physiological flow conditions, the optimum design that provides 11.9% HI reduction and 7.2% efficiency enhancement is selected.
The Longitudinal Danish High Myopia Study, Cohort 1948: at age 66 years visual ability is only occasionally affected by visual field defects
Authors: Fledelius Hans C. , Jacobsen Nina , Li Xiao Q. , Goldschmidt Ernst
Published: October 2018

Purpose

A descriptive study on visual fields, as part of a 50‐year follow‐up of high myopia in an unselected cohort‐based Danish sample, now aged 66 years.

Methods

In a Copenhagen 1948 birth cohort (n = 9243), 39 individuals aged 14 years were identified with myopia of at least −6 D, and with regular clinical follow‐ups since then. In 2002 (n = 34, age 54 years) and 2008 (n = 32, age 60), the individual ambulatory visual field was outlined by kinetic Goldmann large object perimetry (IV or V,4e). At age 66 years, 28 attended for the 2014–2015 follow‐up, at which smaller Goldmann objects (II and I,4e) were added, further to identify relative defects.

Results

Repeated large object perimetry disclosed statistically significant general peripheral narrowing over the 12–13‐year test period, though slight and without practical implications. Two new cases showing absolute defects were however added to the three already known. The addition of small Goldmann objects disclosed relative defects in another eight participants, in some to suggest a refraction‐related pattern (fundus ectasia; uncorrected high myopia). However, comparing eyes with and without defects, statistical importance could not be attached to the degree of myopia, fundus ectasia or optic disc morphology (χ2, n.s.).

Conclusion

(i) Serial large object Goldmann isopters over the ‘senior’ decade up to age 66 demonstrated a slight general peripheral narrowing by age of visual fields in high myopia. (ii) Overall 42% of the participants had absolute or relative defects (in 5 and 8, respectively), however, without socio‐visual consequences when binocular. (iii) Visual field loss by age still appears a minor issue in clinically unselected high myopia.
Predicting the outcome of laser peripheral iridotomy for primary angle closure suspect eyes using anterior segment optical coherence tomography
Authors: Koh Victor , Keshtkaran Mohammad Reza , Hernstadt David , Aquino Maria Cecilia D. , Chew Paul T. , Sng Chelvin
Published: October 2018

Purpose

Develop an algorithm to predict the success of laser peripheral iridotomy (LPI) in primary angle closure suspect (PACS), using pretreatment anterior segment optical coherence tomography (ASOCT) scans.

Methods

A total of 69 eyes with PACS underwent LPI and time‐domain ASOCT scans (temporal and nasal cuts) were performed before and after LPI. After LPI, success is defined as one or more angles changed from closed to open. All the pretreatment ASOCT scans were analysed using the Anterior Segment Analysis Program to derive anterior chamber angle (ACA) measurements. The measurements for each angle were ordered along with angle‐independent measurements totalling to 42 measurements which serve as features for the prediction algorithm. Two masked glaucoma fellowship‐trained ophthalmologists graded the pre‐LPI ASOCT scans to determine whether LPI was likely to successful.

Results

There were 42 (60.9%) eyes that fulfilled the criteria for success after LPI. Iris concavity, angle recess area (750 μm) and iris concavity ratio showed the highest predictive score and were selected using correlation‐based subset selection method. These features were classified into two (‘successful’ and ‘unsuccessful’) categories using a Bayes classifier. The algorithm predicted the success of LPI with 79.28% cross validation accuracy, which was superior to the predictive accuracy of the ophthalmologists (kappa 0.497 and 0.636 respectively).

Conclusion

Using pretreatment ASOCT scans, our algorithm was superior to ophthalmologists in predicting the success of LPI for PACS eyes. This novel algorithm could aid decision making in offering LPI as a prophylaxis for PACS.
Quality of life: fractionated stereotactic radiotherapy versus enucleation treatment in uveal melanoma patients
Authors: van Beek Jackelien G.M. , Buitendijk Gabrielle H.S. , Timman Reinier , Muller Karin , Luyten Gregorius P.M. , Paridaens Dion , Naus Nicole C. , Kiliç Emine
Published: October 2018

Purpose

To report the quality of life and visual functioning in uveal melanoma patients treated with enucleation or fractionated stereotactic radiation therapy (fSRT).

Methods

Uveal melanoma (UM) patients treated with fSRT (n = 65) or enucleation (n = 48) participated in this prospective study. Questionnaires to measure anxiety (State‐Trait Anxiety Inventory), subjective distress (Impact of Event Scale) and quality of life (EORTC‐QLQ‐C30 and National Eye Institute Visual Function Questionnaire (VFQ‐25)) were obtained before treatment and 2, 6, 12, 24, 36 and 48 months after treatment.

Results

Less peripheral vision was observed until 3 years (p = 0.026) posttreatment in enucleated patients compared to irradiated patients. From 2 months until 3 years posttreatment irradiated patients increase in role functioning‐score (p = 0.005), while enucleated patients decrease in score (p = 0.012). Regardless of their treatment, for all patients we measured a reduction in physical functioning (p = 0.035), insomnia (p < 0.001) and in state anxiety from pretreatment until 2 years posttreatment (p < 0.001). An increase in pain overall (p = 0.023) and in emotional functioning is observed 1 year posttreatment (p < 0.001). At baseline, patients with metastases (independent of their treatment) have more subjective distress (p = 0.037) than patients without metastases. The mean ‘global health score’ overall, without effect of time, was 76.4 (SD: 13.6).

Conclusion

Enucleated patients had more difficulty working or performing household tasks 2 months posttreatment compared to irradiated patients. Enucleated patients had diminished peripheral vision until 3 years compared to irradiated patients. Overall quality of life is not significantly different between both treatment groups.
Clinical evidence supporting the use of donor sclera as spacer material in complicated cases of strabismus surgery – retrospective evaluation of surgical results in 117 patients with thyroid‐associated ophthalmopathy or congenital strabismus
Authors: Thorisdottir Rannveig Linda , Blohmé Jonas , Malmsjö Malin
Published: October 2018

Purpose

To examine the outcome of the use of donor sclera as spacer material in complicated cases of strabismus surgery.

Methods

A retrospective cohort study on patients with complicated thyroid‐associated ophthalmopathy (TAO) (n = 42) or congenital strabismus (n = 75). Patients underwent strabismus surgery during 1994–2014. The surgical results were evaluated in terms of the reduction in the angle of deviation, the need for re‐operation, complications and patient satisfaction.

Results

The majority of the TAO patients underwent surgery for vertical strabismus (n = 25). The vertical angle of deviation in the primary position was significantly reduced from a median of 23 prism dioptres (PD) to 2 PD (n = 35, p < 0.001). The horizontal angle of deviation in primary position for TAO patients with esotropia was significantly reduced, from a median of 35 PD to 2 PD (n = 17, p < 0.001). The majority of the congenital cases had horizontal strabismus (esotropia = 29, exotropia = 27). The angle of deviation in esotropia was reduced from a median of 29 PD to 8 PD (n = 36, p < 0.001) and in exotropia from 30 PD to 10 PD (n = 34, p < 0.001). Most of the patients were satisfied with the outcome of surgery, and only 12% required re‐operation within 2 years.

Conclusion

This is the first clinical study on the use of donor sclera as spacer material in complicated cases of strabismus surgery. The surgical results were good in terms of the reduction in the angle of deviation, the need for re‐operation, complications and patient satisfaction, supporting the use of donor sclera for strabismus surgery.
High rate of failed visual‐acuity measurements with the Amsterdam Picture Chart in screening at the age of 36 months
Authors: Telleman Marieke A. J. , Sloot Frea , Benjamins Janine , Simonsz Huibert J.
Published: October 2018

Purpose

In the Netherlands, youth health care physicians and nurses screen all children for general health disorders at Child Health Care Centers. As part of this, the eyes are screened seven times, with the first visual acuity (VA) measurement at 36 months with the Amsterdam Picture Chart (APK). The suitability of the APK has been questioned.

Methods

Children born between July 2011 and June 2012 born in the provinces Drenthe, Gelderland and Flevoland and invited for screening at 36 months were eligible. Parents were sent the APK picture optotypes to practise with their children in advance. Data were collected from electronic screening records. The Dutch vision screening guideline prescribes that children with VA <5/6, or one line interocular difference (not logMAR, however) should be retested or referred.

Results

Of 10 809 eligible children, 1546 did not attend and 602 attended but had no VA measurement at age 36 months, 247 of these were under orthoptic treatment. Of the 8448 children examined, VA was sufficient in 5663 (67.0%) and insufficient in 1312 (15.5%). In 1400 (16.6%), the measurement of VA itself failed. In 73 (0.9%), data were missing. Of the 216 children with 2 failed VA measurements, 150 (69%) were not referred, and measurement of VA was deferred to the next general screening examination at 45 months.

Conclusion

Although most parents had practised the APK picture optotypes at home with their children, the rate of failed APK measurements plus the measurements with insufficient VA was 32.1% at 36 months. Similar rates have previously been reported for Lea Symbols and HOTV, permitting the conclusion that measurement of VA at the age of 36 months cannot be recommended as a screening test in the general population.
Topical cyclosporine‐A versus prednisolone for herpetic stromal keratitis: a randomized controlled trial
Authors: Peyman Alireza , Nayebzadeh Mohamadreza , Peyman Mohamadreza , Afshari Natalie A. , Pourazizi Mohsen
Published: October 2018

Purpose

To compare topical cyclosporine‐A 2% eye drop (Cs‐A) with prednisolone acetate 1% eye drop for treatment of herpetic stromal keratitis (HSK).

Methods

In this randomized clinical trial, 38 eyes of 33 patients with HSK were randomly assigned to receive either 2% Cs‐A or 1% prednisolone acetate eye drops. All subjects received oral acyclovir 400 mg twice a day. Slit‐lamp examination, Scheimpflug tomography corneal optical densitometry (Pentacam®, Oculus Inc., Wetzlar, Germany), best‐corrected visual acuity (BCVA), and intra‐ocular pressure (IOP) were evaluated at the first visit, and 14 and 30 days after the treatment.

Results

Within‐group analysis revealed significant improvement of total cornea optical density after 30 days of treatment in both groups (30.3 ± 10.5 to 28.3 ± 9.8, p < 0.001 for prednisolone group, and 30.5 ± 8.8 to 28.8 ± 8.3 p < 0.001 for Cs‐A group, mean ± SD). We were not able to disclose any significant difference between the two groups regarding the improvement of cornea optical density (p = 0.66). Best‐corrected visual acuity (BCVA) logMAR significantly improved in both groups after 30 days of treatment (0.20 ± 0.52, p = 0.002 in prednisolone group, and 0.24 ± 0.31, p < 0.001 in Cs‐A group, mean ± SD). Analysis between groups did not show a significant difference of BCVA improvement (p = 0.45). We did not observe any severe side effect attributable to drugs.

Conclusions

Cs‐A 2% and prednisolone acetate 1% topical eye drops are effective for treatment of HSK.
Letter: identifying coeliac disease among patients with bloating
Authors: Ellul P. , Zammit C.
Published: October 2018

Linked Content

This article is linked to Hujoel et al and Hujoel and Rubio‐Tapia papers. To view these articles visit https://doi.org/10.1111/apt.14625 and https://doi.org/10.1111/apt.14964.
Editorial: clinical features and outcomes of hepatocellular carcinoma in Caucasian cirrhotic patients on long‐term analogue therapy for HBV
Authors: Stratton Leanne , Bathgate Andrew
Published: October 2018

Linked Content

This article is linked to Loglio et al paper. To view this article visit https://doi.org/10.1111/apt.14848.
Effects of maturation and size on population pharmacokinetics of pentoxifylline and its metabolites in very preterm infants with suspected late‐onset sepsis or necrotizing enterocolitis: a pilot study incorporating clinical outcomes
Authors: Salman Sam , Hibbert Julie , Page‐Sharp Madhu , Manning Laurens , Simmer Karen , Doherty Dorota A. , Patole Sanjay , Batty Kevin T. , Strunk Tobias
Published: October 2018

Aims

Infection‐induced inflammation is associated with adverse long‐term outcomes in preterm infants. Pentoxifylline (PTX) is a candidate for adjunct immunomodulatory therapy in preterm infants with late‐onset sepsis (LOS) and necrotizing enterocolitis (NEC), but pharmacokinetic data in this population are extremely limited. This study aims to characterize the pharmacokinetic properties of intravenous PTX and its metabolites in preterm infants.

Method

An open label pilot clinical study of intravenous PTX as an adjunct therapy in preterm infants (gestation <32 weeks) with suspected LOS or NEC was undertaken. PTX was infused for 12 h for two days (60 mg kg−1 per 12 h), and in infants with confirmed diagnosis of LOS or NEC, for 6 h for another 4 days (30 mg kg−1 per 6 h). Plasma concentrations of PTX and its principal metabolites from collected blood samples were measured using a validated LCMS assay. NONMEM was used to analyse the data using population pharmacokinetic modelling.

Results

The preterm infants (n = 26) had a median (range) gestation of 24.8 weeks (23.3–30.4) and birthweight of 689 g (370–1285). PTX was well tolerated and without treatment‐limiting adverse effects. Changes in size (weight) and maturation were successfully modelled for PTX and metabolites. After allometric scaling, clearance increased with postmenstrual age, increasing by approximately 30% per week for PTX and M1 (lisofylline) and simulations of current dosing demonstrated a six‐fold difference in exposure between 24 and 35 weeks postmenstrual age.

Conclusions

The developed model can be used to explore dosing strategies based on size and maturation for preterm infants.
Discontinuation of antidepressants in suicides findings from the Friuli Venezia Giulia Region, Italy, 2005‐2014
Authors: Castelpietra Giulio , Bortolussi Luca , Gobbato Michele , Arnoldo Luca , Balestrieri Matteo , Wettermark Bjorn
Published: October 2018

Although continued use of antidepressants (AD) has been found to be associated with a lower risk of suicide, AD discontinuation is reported repeatedly. The aim of this case‐control study, thus, was to assess whether discontinuation to AD was associated with an increased risk of suicide, according to different genders and age groups. The Social and Health Information System of Friuli Venezia Giulia Region, Italy, was used to collect data on suicides, diagnoses and AD use from 2005 to 2014. We selected, as cases, all suicides that had at least one prescription of AD in the 730 days before death (N = 876), and we matched with regard to age and sex each case with five controls from the general population. Conditional logistic regression analyses were used to assess the association between suicide and modifications of AD treatment. We found that 70% of suicides and controls from the general population discontinued AD in the 2 years before the index date. In two‐thirds of them, discontinuations were two or more. Discontinuation of AD, however, did not represent a significant risk factor for suicide. More appropriate care of depression, particularly by primary care physicians who widely prescribe AD, should be fostered in order to prevent suicide. However, more research is needed to assess to which extent AD discontinuation can affect suicidal risk.
Polymorphisms associated with fentanyl pharmacokinetics, pharmacodynamics and adverse effects
Authors: Saiz‐Rodríguez Miriam , Ochoa Dolores , Herrador Coral , Belmonte Carmen , Román Manuel , Alday Enrique , Koller Dora , Zubiaur Pablo , Mejía Gina , Hernández‐Martínez María , Abad‐Santos Francisco
Published: October 2018

Fentanyl is an agonist of the μ‐opioid receptor commonly used in the treatment of moderate‐severe pain. In order to study whether pharmacogenetics explains some of the variability in the response to fentanyl, several genes related to fentanyl receptors, transporters and metabolic enzymes have been analysed. Thirty‐five healthy volunteers (19 men and 16 women) receiving a single 300 μg oral dose of fentanyl were genotyped for 9 polymorphisms in cytochrome P450 (CYP) enzymes (CYP3A4 and CYP3A5), ATP‐binding cassette subfamily B member 1 (ABCB1), opioid receptor mu 1 (OPRM1), catechol‐O‐methyltransferase (COMT) and adrenoceptor beta 2 (ADRB2) by real‐time PCR. Fentanyl concentrations were measured by ultra‐performance liquid chromatography combined with tandem mass spectrometry (UPLC‐MS/MS). Fentanyl pharmacokinetics is affected by sex. Carriers of the CYP3A4*22 allele, which is known to reduce the mRNA expression, showed higher area under the concentration‐time curve (AUC) and lower clearance (Cl) values. Although this finding might be of importance, its validity needs to be confirmed in other similar settings. Furthermore, carriers of the ABCB1 C1236T T/T genotype presented a lower AUC and higher Cl, as well as lower half‐life (T1/2). As volunteers were blocked with naltrexone, the effect of fentanyl on pharmacodynamics might be biased; however, we could observe that fentanyl had a hypotensive effect. Moreover, ADRB2 C523A A allele carriers showed a tendency towards reducing systolic blood pressure. Likewise, OPRM1 and COMT minor allele variants were risk factors for the development of somnolence. CYP3A5*3, ABCB1 C3435T and ABCB1 G2677T/A were not associated with fentanyl's pharmacokinetics, pharmacodynamics and safety profile.
Congenital malformations are associated with secondhand smoke among nonsmoking women: A meta‐analysis
Authors: Zheng Zan , Xie GuoHong , Yang Tubao , Qin Jiabi
Published: October 2018

Background

The association between active maternal smoking and congenital malformations is well established, but little is known about the association between secondhand smoke and congenital malformations. Moreover, studies regarding the association between congenital malformations and secondhand smoke have not yielded consistent results.

Methods

In July 2018, we searched PubMed, EMBASE, and China Biology Medicine databases for observational studies characterizing the relationship between secondhand smoke and congenital malformations of offspring in nonsmoking women. Two reviewers independently decided on whether a study should be included, did data extraction, and assessed study quality. Pooled risks with 95% confidence intervals were calculated using either the fixed‐effects models or random‐effects models. Further subgroup analyses and sensitivity analyses were performed to explore the potential source of heterogeneity and to examine the robustness of risk estimates.

Results

Thirty‐three studies with a total of 31 944 cases and 32 335 controls were included. Secondhand smoke exposure was associated with an increased risk of congenital malformations (odds ratio = 1.92; 95% confidence interval 1.61‐2.30). Secondhand smoke was correlated with significantly increased risk for digestive system (1.17 [1.05‐1.32]), nervous system (1.74 [1.33‐2.29]), and cardiovascular system (2.10 [1.32‐3.35]) malformations and for oral clefts (1.87 [1.47‐2.39]).

Conclusions

Secondhand smoke exposure increases the risk for overall and several organ‐system malformations. These findings highlight the necessity of improving community awareness to prevent secondhand smoke exposure during the preconception and conception periods.
Is there a burden attached to synaesthesia? Health screening of synaesthetes in the general population
Authors: Carmichael Duncan A. , Smees Rebecca , Shillcock Richard C. , Simner Julia
Published: October 2018

Synaesthesia has long been considered a benign alternative form of perception most often associated with positive rather than negative outcomes. The condition has been associated with a variety of cognitive and perceptual advantages, including benefits in memory, processing speed, and creativity. It is not currently recognized in the DSM‐IV. Recently, however, several studies have raised the question of a possible link between synaesthesia and clinical conditions. Here, we present the first large‐scale screening of the general population in which we (1) objectively identified grapheme‐colour synaesthetes and (2) elicited information from our participants about a range of clinical conditions. We compared the prevalence rates of these conditions in synaesthetes versus non‐synaesthetes to establish whether any conditions were found at a higher rate among synaesthetes. In our initial study, screening 3,742 people (95 synaesthetes and 3,647 controls), we found initially that grapheme‐colour was significantly comorbid with two conditions (anxiety disorder and obsessive compulsive disorder). In our second study, screening a new population of 120 synaesthetes and 166 non‐synaesthetes, we replicated our finding that grapheme‐colour synaesthesia is comorbid with anxiety disorder. At the same time, we also addressed a methodological concern that likely elevated rates of OCD in Study 1. We consider the aetiology of synaesthesia to determine whether there may be a shared genetic or neurological basis with anxiety disorder, and we question the status of synaesthesia within a mental health framework.
Changing trends in the endourological management of urolithiasis in anomalous kidneys
Authors: Singh Abhishek G. , Jairath Ankush , Balaji Sudharshan S. , Tak Gopal , Ganpule Arvind P. , Vijayakumar Mohankumar , Sabnis Ravindra B. , Desai Mahesh R.
Published: October 2018

Objectives

To present our single‐centre experience of urolithiasis management in anomalous kidneys, highlighting the need for an algorithm‐based approach in deciding the appropriate treatment method for each type.

Patients and Methods

We retrospectively reviewed the data of all the patients who presented to our renal unit with urolithiasis in an anomalous kidney between January 1990 and July 2014. The peri‐operative characteristics of all the patients, along with management approach, were studied.

Results

Percutaneous nephrolithotomy (PCNL) was the most common surgical technique used, followed by flexible ureterorenoscopy (URS). Pain was the most common presentation in these patients. The overall stone clearance rate associated with PCNL and flexible URS was 85.8% in cases of anomalous kidneys in this series. The stone clearance rates in ectopic kidneys, horseshoe kidneys, malrotated kidneys and autosomal dominant polycystic kidneys associated with PCNL and flexible URS were similar: 86%, 88%, 76% and 83%, respectively, and 81.2%, 80%, 92% and 100%, respectively . Based on our results, we developed a stone management algorithm.

Conclusion

The management of renal calculi in patients with renal anomalies may vary based on the stone size, location, density, pelvicalyceal system anatomy and drainage. An algorithm‐based approach could help surgeons decide the appropriate treatment in this population.
DNA repair defects in prostate cancer: impact for screening, prognostication and treatment
Authors: Warner Evan W. , Yip Steven M. , Chi Kim N. , Wyatt Alexander W.
Published: October 2018

Failure of effective DNA damage repair is a hallmark of cancer, but was previously underappreciated as a driver of aggressive prostate cancer. However, recent international sequencing efforts have revealed that both germline and somatic alterations within the homologous recombination and mismatch repair pathways are relatively common in lethal metastatic disease. BRCA2 gene alterations are particularly prevalent and are linked to poor prognosis as well as poor responses to systemic therapy for castration‐resistant prostate cancer, although there is conflicting support for the latter. Defective DNA repair contributes to tumour heterogeneity, evolution and progression, but there are high hopes that management of this aggressive subset will be transformed by biomarker‐driven use of poly‐ADP ribose polymerase (PARP) inhibitors and platinum‐based chemotherapy. In this review, we detail the relationship between DNA repair defects and prostate cancer, highlighting the prevalence of mutations in key genes and their controversial association with clinical outcomes.
Prostate cancer mortality rates in Peru and its geographical regions
Authors: Torres‐Roman Junior Smith , Ruiz Eloy F. , Martinez‐Herrera Jose Fabian , Mendes Braga Sonia Faria , Taxa Luis , Saldaña‐Gallo Jorge , Pow‐Sang Mariela R. , Pow‐Sang Julio M. , La Vecchia Carlo
Published: October 2018

Objective

To evaluate the mortality rates for prostate cancer according to geographical areas in Peru between 2005 and 2014.

Materials and Methods

Information was extracted from the Deceased Registry of the Peruvian Ministry of Health. We analysed age‐standardised mortality rates (world population) per 100 000 men. Spatial autocorrelation was determined according to the Moran Index. In addition, we used Cluster Map to explore relations between regions.

Results

Mortality rates increased from 20.9 (2005–2009) to 24.1 (2010–2014) per 100 000 men, an increase of 15.2%. According to regions, during the period 2010–2014, the coast had the highest mortality rate (28.9 per 100 000), whilst the rainforest had the lowest (7.43 per 100 000). In addition, there was an increase in mortality in the coast and a decline in the rainforest over the period 2005–2014. The provinces with the highest mortality were Piura, Lambayeque, La Libertad, Callao, Lima, Ica, and Arequipa. Moreover, these provinces (except Arequipa) showed increasing trends during the years under study. The provinces with the lowest observed prostate cancer mortality rates were Loreto, Ucayali, and Madre de Dios. This study showed positive spatial autocorrelation (Moran's I: 0.30, P = 0.01).

Conclusion

Mortality rates from prostate cancer in Peru continue to increase. These rates are higher in the coastal region compared to those in the highlands or rainforest.
Phase II clinical trial of S‐1 plus nanoparticle albumin‐bound paclitaxel in untreated patients with metastatic gastric cancer
Authors: He Ming‐ming , Wang Feng , Jin Ying , Yuan Shu‐qiang , Ren Chao , Luo Hui‐yan , Wang Zhi‐qiang , Qiu Miao‐zhen , Wang Zi‐xian , Zeng Zhao‐lei , Li Yu‐hong , Wang Feng‐hua , Zhang Dong‐sheng , Xu Rui‐hua
Published: October 2018

The present study is the first phase II clinical trial aimed to evaluate the efficacy and safety of S‐1 plus nanoparticle albumin‐bound paclitaxel (Nab‐PTX) as first‐line chemotherapy for advanced gastric cancer (AGC). Previously untreated patients with metastatic gastric adenocarcinoma received S‐1 in oral doses of 40 mg (BSA <1.25 m2), 50 mg (1.25 ≤ BSA < 1.50 m2) and 60 mg (BSA ≥1.50 m2) b.i.d. on days 1‐14 in combination with Nab‐PTX (120 mg/m2, on days 1 and 8) for each 21‐day cycle. Primary endpoint was progression‐free survival (PFS), and secondary endpoints were overall response rate (ORR), overall survival (OS), disease control rate (DCR), and toxicity. A total of 73 gastric cancer patients with metastatic and measurable lesions were enrolled in the first‐line setting. Median PFS and OS were 9.63 months and 14.60 months, respectively. Four (5.5%) patients had complete responses, 39 (53.4%) had partial responses (PRs), 21 (28.8%) had stable disease, four (5.5%) progressed and five (6.8%) were not evaluable. ORR and DCR were 58.9% and 87.7%, respectively. Most toxicities were mild, and no treatment‐related deaths occurred. Grade 3 to 4 toxicities occurred in 22 patients (30.1%) as follows: leukopenia (13.7%), neutropenia (12.3%), anemia (5.5%), thrombocytopenia (1.4%), diarrhea (6.8%), vomiting (2.7%), stomatitis (1.4%), peripheral neuropathy (1.4%), and hand‐foot syndrome (1.4%). Seven patients achieved good responses and underwent gastrectomy plus metastasectomy. Thirty (41.1%) patients had S‐1 maintenance with a median of four cycles. S‐1 plus Nab‐PTX is an efficient and safe regimen as first‐line treatment for patients with AGC.
p53‐inducible gene 3 promotes cell migration and invasion by activating the FAK/Src pathway in lung adenocarcinoma
Authors: Gu Meng‐Meng , Gao Dexuan , Yao Ping‐An , Yu Lan , Yang Xiao‐Dong , Xing Chun‐Gen , Zhou Jundong , Shang Zeng‐Fu , Li Ming
Published: October 2018

The p53‐inducible gene 3 (PIG3) is one of the p53‐induced genes at the onset of apoptosis, which plays an important role in cell apoptosis and DNA damage response. Our previous study reported an oncogenic role of PIG3 associated with tumor progression and metastasis in non‐small cell lung cancer (NSCLC). In this study, we further analyzed PIG3 mRNA expression in 504 lung adenocarcinoma (LUAD) and 501 lung squamous cell carcinoma (LUSC) tissues from The Cancer Genome Atlas database and we found that PIG3 expression was significantly higher in LUAD with lymph node metastasis than those without, while no difference was observed between samples with and without lymph node metastasis in LUSC. Gain and loss of function experiments were performed to confirm the metastatic role of PIG3 in vitro and to explore the mechanism involved in its oncogenic role in NSCLC metastasis. The results showed that PIG3 knockdown significantly inhibited the migration and invasion ability of NSCLC cells, and decreased paxillin, phospho‐focal adhesion kinase (FAK) and phospho‐Src kinase expression, while its overexpression resulted in the opposite effects. Blocking FAK with its inhibitor reverses PIG3 overexpression‐induced cell motility in NSCLC cells, indicating that PIG3 increased cell metastasis through the FAK/Src/paxillin pathway. Furthermore, PIG3 silencing sensitized NSCLC cells to FAK inhibitor. In conclusion, our data revealed a role for PIG3 in inducing LUAD metastasis, and its role as a new FAK regulator, suggesting that it could be considered as a novel prognostic biomarker or therapeutic target in the treatment of LUAD metastasis.
Japanese guidelines for dimethyl fumarate
Authors: Niino Masaaki , Ohashi Takashi , Ochi Hirofumi , Nakashima Ichiro , Shimizu Yuko , Matsui Makoto
Published: October 2018

A multicenter, randomized, double‐blind, placebo‐controlled, efficacy and safety study ofBG00012 in participants from the Asia–Pacific region and other countries with relapsing–remitting multiple sclerosis (APEX), including Japan, established the efficacy of dimethyl fumarate (DMF) in preventing relapses and disease progression in patients with multiple sclerosis (MS). Consequently, in December 2016,DMFwas approved as the second oral disease‐modifying drug forMSin Japan. However, the new Japanese guidelines forMSand neuromyelitis optica published in 2017 did not includeDMF. Later, after the committee discussed a guideline forDMF, a supplement of the new guidelines forMSand neuromyelitis optica, which includedDMF, was published in June 2018; this supplement comprised the following four clinical questions: (i) isDMFeffective in preventing relapses in patients withMS?; (ii) isDMFeffective in preventing disease progression in patients withMS?; (iii) how to useDMF?; and (iv) what adverse events doesDMFpossibly cause? Furthermore, the supplement comprised answers to the questions and comments. Overall, this supplement is anticipated to contribute toward the treatment of JapaneseMSpatients withDMF.
Predicting the time needed for environmental systematic reviews and systematic maps
Authors: Haddaway Neal R. , Westgate Martin J.
Published: October 2018

Systematic reviews (SRs) and systematic mapping aim to maximize transparency and comprehensiveness while minimizing subjectivity and bias. These are time‐consuming and complex tasks, so SRs are considered resource intensive, but published estimates of systematic‐review resource requirements are largely anecdotal. We analyzed all Collaboration for Environmental Evidence (CEE) SRs (n= 66) and maps (n= 20) published from 2012 to 2017 to estimate the average number of articles retained at each review stage. We also surveyed 33 experienced systematic reviewers to collate information on the rate at which those stages could be completed. In combination, these data showed that the average CEE SR takes an estimated 164 d (full‐time equivalent) (SD 23), and the average CEE systematic map (SM) (excluding critical appraisal) takes 211 d (SD 53). While screening titles and abstracts is widely considered time‐consuming, metadata extraction and critical appraisal took as long or longer to complete, especially for SMs. Given information about the planned methods and evidence base, we created a software tool that predicts time requirements of a SR or map with evidence‐based defaults as a starting point. Our results shed light on the most time‐consuming stages of the SR and mapping processes, will inform review planning, and can direct innovation to streamline processes. Future predictions of effort required to complete SRs and maps could be improved if authors provide more details on methods and results.
Ecological stoichiometry and nutrient partitioning in two insect herbivores responsible for large‐scale forest disturbance in the Fennoscandian subarctic
Authors: Metcalfe Daniel B. , Cherif Mehdi , Jepsen Jane U. , Vindstad Ole Petter L. , Kristensen Jeppe Å. , Belsing Ulrika
Published: October 2018

1. Outbreaks of herbivorous insects can have large impacts on regional soil carbon (C) storage and nutrient cycling. In northernmost Europe, population outbreaks of several geometrid moth species regularly cause large‐scale defoliation in subarctic birch forests. An improved understanding is required of how leaf C and nutrients are processed after ingestion by herbivores and what this means for the quantity and quality of different materials produced (frass, bodies).

2. In this study, larvae of two geometrid species responsible for major outbreaks (Epirrita autumnata and Operophtera brumata) were raised on exclusive diets of Betula pubescens var. czerepanovii (N. I. Orlova) Hämet Ahti and two other abundant understorey species (Betula nana, Vaccinium myrtillus). The quantities of C, nitrogen (N) and phosphorus (P) ingested and allocated to frass, bodies and (in the case of C) respired were recorded.

3. Overall, 23%, 70% and 48% of ingested C, N and P were allocated to bodies, respectively, rather than frass and (in the case of C) respiration. Operophtera brumata consistently maintained more constant body stoichiometric ratios of C, N and P than did E. autumnata, across the wide variation in physico‐chemical properties of plant diet supplied.

4. These observed differences and similarities on C and nutrient processing may improve researchers' ability to predict the amount and stoichiometry of frass and bodies generated after geometrid outbreaks.
The microbiome of the “sterile” pustules in palmoplantar pustulosis
Authors: Masuda‐Kuroki Kana , Murakami Masamoto , Tokunaga Naohito , Kishibe Mari , Mori Hideki , Utsunomiya Ryo , Tsuda Teruko , Shiraishi Ken , Tohyama Mikiko , Sayama Koji
Published: October 2018

The skin microbiome influences skin pathophysiology. Palmoplantar pustulosis (PPP) is a chronic skin disease characterized by infectious‐like pustules on the palms and soles. These pustules are thought to be sterile because bacterial cultures obtained from the pustules are negative. However, culture methods are limited in their ability to identify all bacteria on the skin. We hypothesized that the “sterile” pustules of PPP do not lack bacteria, but rather contain a microbiome. To test this hypothesis, we identified bacteria in “sterile” pustules using non‐culture methods. We conducted Sanger and 16S rRNA sequencing using primers specific to the V1‐V2 region in PPP‐pustulovesicles (PVs) (n = 43) and pompholyx vesicle fluids (n = 15). Sanger sequencing identified some Staphylococcus, Propionibacterium, Streptococcus and Pyrinomonas species in PPP‐PVs but failed to identify any bacteria in most of the pompholyx vesicles. 16S rRNA sequencing of PPP‐PVs indicated the presence of a microbiome that included various phyla, including Firmicutes, Proteobacteria, Actinobacteria and Bacteroidetes. At the genus level, smokers had higher levels of Staphylococcus in PPP‐PVs compared with non‐smokers. These results indicate that a microbiome exists in “sterile” pustules of PPP and that PPP smokers had higher levels of Staphylococcus in pustules. It is therefore necessary to reconsider the pathogenesis of PPP from the perspective of the microbiome.
Father–Daughter Bonds: A Comparison of Adolescent Daughters' Relationships With Resident Biological Fathers and Stepfathers
Authors: Campbell Cynthia G. , Winn Elizabeth J.
Published: October 2018

Objective

To investigate whether the interpersonal dynamics of closeness are different in stepfather–stepdaughter versus father–daughter relationships during adolescence.

Background

Establishing a general process model of the relational factors contributing to greater closeness between fathers and daughters is a preliminary step toward examining variations in such processes.

Method

The data were from the National Longitudinal Study of Adolescent to Adult Health, a nationally representative sample of adolescents. Respondents were female adolescents who were living with either a biological father (n = 1,881) or stepfather (n = 273) and reported on the availability and involvement of their (step)fathers, as well as the communication and closeness in their relationship with him.

Results

Involvement and communication were predictors of closeness in both types of relationships, however, communication was a stronger predictor of closeness between stepfathers and stepdaughters. For adolescent girls living with a stepfather, greater involvement with their stepfathers was associated with greater closeness to their nonresident biological fathers. The length of the relationship between stepfathers and stepdaughters was not associated with levels of closeness.

Conclusions

Overall, these findings suggest that stepfather–stepdaughter relationships reflect similar interpersonal dynamics as father–daughter relationships but that establishing and maintaining these relationships through meaningful communication may be particularly important for stepfathers and stepdaughters.

Implications

Practitioners working to help stepfamilies build stronger relationships may want to stress that investing in shared activities and maintaining meaningful communication can be particularly important for establishing and maintaining positive relationships between stepfathers and stepdaughters.
Alterations of EDEM1 functions enhance ATF6 pro‐survival signaling
Authors: Papaioannou Alexandra , Higa Arisa , Jégou Gwénaële , Jouan Florence , Pineau Raphael , Saas Laure , Avril Tony , Pluquet Olivier , Chevet Eric
Published: October 2018

Activating transcription factor 6 alpha (referred to as ATF6 hereafter) is an endoplasmic reticulum (ER)‐resident glycoprotein and one of the three sensors of the unfolded protein response (UPR). Upon ER stress, ATF6 is exported to the Golgi complex where it is cleaved by the S1P and S2P proteases thus releasing ATF6 cytosolic fragment and leading to the transcription of ATF6 target genes. In this study, we performed a phenotypic small‐interfering RNA (siRNA) screening to better characterize the ER mechanisms involved in ATF6 activation upon ER stress. This revealed that silencing of ER‐degradation‐enhancing alpha‐mannosidase‐like protein‐1 (EDEM1) increased the bioavailability of ER stress‐induced ATF6 export to the Golgi complex through the stabilization of the natively unstable ATF6 protein. Moreover, we characterized a somatic variant of EDEM1 (N198I) found in hepatocellular carcinoma that alters ATF6 signaling and might provide a selective advantage to the transforming cells. Hence, our work confirms the natively unstable nature of ATF6 and links this property to potentially associated pro‐oncogenic functions.
Northward expansion of the bivoltine life cycle of the cricket over the last four decades
Authors: Matsuda Naoki , Tanaka Kazuhiro , Watari Yasuhiko , Shintani Yoshinori , Goto Shin G. , Nisimura Tomoyosi , Izumi Yohei , Numata Hideharu
Published: October 2018

Recent climate warming has affected some life‐history traits of insects, including voltinism and body size. The magnitude of changes in these traits may differ latitudinally within a species because of the differing lengths of season available for growth. The present study aims to estimate the change in voltinism of the lawn ground cricket, Polionemobius mikado (Shiraki) (Orthoptera: Trigonidiidae), over the last four decades by comparing the body size between adults collected from a wide range of latitudes in Japan in recent years (2015–2017) and those collected four decades ago (1969–1976). The body size of adults collected in recent years showed a latitudinal saw‐tooth cline, in the same way as body size did four decades ago, and the cline shifted northward over the last four decades: In 2015–2017, the body size decreased slightly with increasing latitude from 31°N to 36°N, and then increased to 40°N, and again decreased from 40°N to 44°N. Comparison of the body size between recent years and four decades ago revealed that the body size has decreased significantly at the middle latitudes (36–40°N), suggesting that the proportion of smaller bivoltine individuals there has increased over the last four decades. The sum of effective temperatures for postdiapause embryonic development at around 36°N in recent years was comparable to that at 31–35°N four decades ago, at which P. mikado populations were bivoltine. Taken together, these findings suggested that the latitudinal range suitable for the bivoltine life cycle of P. mikado has expanded northward over the last four decades because of climate warming. This is the first report that shows that a decrease in body size can be caused by climate warming via an increase in voltinism.
Validation of the Spanish version of the Cancer Symptom Scale in Hispanic cancer patients
Authors: Gonzalez‐Mercado Velda Janet , Saligan Leorey N. , Rodriguez Carmen S. , Ortiz Desiree , Pedro Elsa , McMillan Susan C.
Published: October 2018

Aim

To assess the validity of the translated Spanish Cancer Symptom Scale.

Background

Instruments to facilitate comprehensive and objective assessments of the cancer symptom experience in underrepresented populations are essential.

Methods

The Cancer Symptom Scale was translated into Spanish, and a back translation was conducted. During June 2016, a sample of 121 Hispanic Puerto Rican patients with any cancer diagnosis, all undergoing cancer treatments, completed four paper surveys. A subgroup of 15 patients agreed to complete the Spanish Cancer Symptom Scale a second time after a short delay of 1 to 2 hours. Construct validity and reliability (internal consistency via Cronbach alpha and test‐retest reliability) was evaluated.

Results

All the Intensity Items of the Spanish Cancer Symptom Scale correlated significantly with the matched items on the MD Anderson Symptom Inventory. In a subgroup of 77 participants, each Cancer Symptom Scale subscale total of scores correlated significantly with the total scores from the Functional Assessment of Cancer Therapy‐General. Discriminant validity was demonstrated between those receiving chemotherapy and those from post treatment. The Spanish Cancer Symptom Scale internal consistency reliability was 0.98.

Conclusion

The Spanish Cancer Symptom Scale has excellent evidence of validity and reliability for assessing cancer‐therapy‐related symptoms.
Trends in adverse drug reaction‐related hospitalisations over 13 years in New South Wales, Australia
Authors: Zhang Hanwen , Du Wei , Gnjidic Danijela , Chong Shanley , Glasgow Nicholas
Published: October 2018

Background

Adverse drug reactions (ADR) are severe problems in global public health, and result in high mortality and morbidity. Various trends of ADR‐related hospitalisations have been studied in many countries, while estimates of the trends in Australia are limited.

Aim

To examine trends in ADR‐related hospitalisations in New South Wales (NSW).

Methods

Data were extracted from the Admitted Patient Data Collection, a census of hospital separations in NSW. We estimated age‐adjusted rates of ADR‐related hospitalisation between 1 July 2001 and 30 June 2014 and rates by patient characteristics, main therapeutic medication groups and clinical condition groups that warranted the hospitalisation. We used the percentage change annualised estimator to evaluate rates over time.

Results

A total of 315 274 NSW residents admitted for urgent care of ADR was identified. The age‐adjusted rates of ADR‐related hospitalisations nearly doubled and increased by 5.8% (95% CI: 5.0–6.6%) per annum, with an in‐hospital death rate increase of 2.4% (1.6–3.3%). Agranulocytosis (2.7%), nausea and vomiting (2.4%) and heart failure (2.4%) were the most common conditions that led to ADR‐related hospitalisations over 13 years, with acute renal failure (1.4%) recently emerging as the leading adverse condition. Participants aged between 65 and 84 years accounted for nearly half of ADR hospitalisations (45.6%), with age‐adjusted rate increasing from 103.9 in 2001–2002 to 189.0 per 100 000 NSW residents in 2013–2014. Anticoagulants (13.5%) were the most common medications contributing to ADR‐related hospitalisation, followed by opioid analgesics (9.6%).

Conclusion

ADR‐related hospitalisation remains a population health burden, with significant increase over time. The findings call for continuing efforts to prevent ADR, especially among high‐risk populations, such as older people.