bluuebunny/crossref_metadata_2025_split huggingface dataset:
High‐dose linaclotide is effective and safe in patients with chronic constipation: A phase III randomized, double‐blind, placebo‐controlled study with a long‐term open‐label extension study in Japan
Authors: Fukudo Shin , Miwa Hiroto , Nakajima Atsushi , Kinoshita Yoshikazu , Kosako Masanori , Hayashi Kenta , Akiho Hiraku , Kuroishi Kentaro , Johnston Jeffrey M , Currie Mark , Ohkusa Toshifumi 
Published: October 2018

AbstractBackgroundA previous phase II dose‐ranging study of linaclotide in a Japanese chronic constipation (CC) population showed that 0.5 mg was the most effective dose. This study aimed to verify the hypothesis that 0.5 mg of linaclotide is effective and safe in Japanese CC patients.MethodsThis was a Japanese phase III randomized, double‐blind, placebo‐controlled (part 1), and long‐term, open‐label extension (part 2) study of linaclotide. CC patients (n = 186) diagnosed using the Rome III criteria were randomly assigned to linaclotide 0.5 mg (n = 95) or placebo (n = 91) for a 4‐week double‐blind treatment period in part 1, followed by an additional 52 weeks of open‐label treatment with linaclotide in part 2. The primary efficacy endpoint was the change from baseline in weekly spontaneous bowel movement (SBM) frequency at the first week. Secondary endpoints included responder rate for complete SBM (CSBM), changes in stool consistency, and severity of straining.Key ResultsPart 1: Change in weekly mean SBM frequency in the first week of treatment with linaclotide (4.02) was significantly greater than that with placebo (1.48, P < 0.001). Linaclotide produced a higher CSBM responder rate (52.7%) compared to placebo (26.1%, P < 0.001). Part 2: Patients continued to show improved SBM frequency with linaclotide. Through parts 1 and 2, the most common drug‐related adverse event was mild and occasionally moderate diarrhea.Conclusions and InferencesThe results of this study indicate that a linaclotide dose of 0.5 mg/day is effective and safe in Japanese CC patients.
Linaclotide increases cecal pH, accelerates colonic transit, and increases colonic motility in irritable bowel syndrome with constipation
Authors: Farmer Adam D. , Ruffle James K. , Hobson Anthony R. 
Published: October 2018

AbstractBackgroundLinaclotide is efficacious in the management of irritable bowel syndrome with constipation (IBS‐C), yet relatively little is known regarding its effect on human gastrointestinal physiology. The primary aim of the study was to examine the effect of linaclotide on change in pH across the ileocecal junction (ICJ), a proposed measure of cecal fermentation, and its relationship to symptoms and quality of life (QoL) in IBS‐C.MethodsA total of 13 participants with Rome III IBS‐C underwent a standardized wireless motility capsule (WMC). Stool consistency was measured using the Bristol stool form scale (BSFS) and frequency with spontaneous bowel movements (SBM). Gastrointestinal symptoms and QoL were assessed using validated questionnaires. The WMC and questionnaires were repeated after 28 days of linaclotide 290 g po od.Key ResultsLinaclotide reduced the change in pH across the ICJ (−2.4 ± 0.2 vs −2.1 ± 0.4, P = 0.01) as a function of a relative alkalinization of the cecum (5.2 ± 0.2 vs 5.5 ± 0.3, P = 0.02). Linaclotide accelerated colonic transit time (2650 minutes (2171‐4038) vs. 1757 (112‐3011), P = 0.02), increased colonic log motility index (15 ± 1.8 vs. 16.5 ± 1.8, P = 0.004) but had no effect of gastric emptying or small bowel transit. Change in pH across the ICJ correlated with improvement in symptom intensity, unpleasantness, and visceral sensitivity index (r = 0.62, P = 0.03, r = 0.63, P = 0.02, r = 0.62, P = 0.02) and with increases in BSFS type and SBM (r = 0.9, P < 0.0001, r = 0.6, P = 0.02).Conclusions & InferencesLinaclotide's effects are confined to the colon where it increases cecal pH, potentially representing a reduction in cecal fermentation and accelerates colonic motility.
The cancellability test for conversational implicatures
Authors: Zakkou Julia 
Published: October 2018

AbstractMany people follow Grice in thinking that all conversational implicatures are cancellable. And often enough, they use this insight as a test for conversational implicatures. If you want to find out whether something is a conversational implicature, the test has it, you should ask yourself whether the thing in question is cancellable; if you find that it is not cancellable, you can infer that it is not a conversational implicature. If you find that it is cancellable, you can infer that it might well be a conversational implicature and that you should now do further testing. Various philosophers and linguists have questioned the test however. Some have held that Grice's cancellability claim is subject to counterexamples and that the test is not reliable. Others have argued that even though Grice's claim can be defended against the examples in question, the test is not as informative as people have hoped. This article provides an overview of the recent discussion on the cancellability test and suggests a way forward.
Impact of donor and recipient cytomegalovirus serology on long‐term survival of heart transplant recipients
Authors: Mabilangan Curtis , Preiksaitis Jutta K. , Cervera Carlos ,   University of Alberta Cardiothoracic Transplant Group
Published: October 2018

AbstractBackgroundSome studies have shown that pre‐transplant cytomegalovirus (CMV) serostatus is associated with heart transplant patient survival while others have not. We analyzed the relationship between pre‐transplant donor/recipient CMV serostatus and long‐term mortality in a retrospective cohort of heart transplant recipients at our center.MethodsAdult (Age >17 years) heart recipients transplanted between July 1985‐December 2015 were analyzed. Variables included age, sex, pre‐transplant donor (D)/recipient (R) serostatus [D−/R−, D−/R+, D+/R+, D+/R−], CMV infection within 2 years of transplant and transplant eras divided by changes in CMV prevention strategies: Era 1 (Pre‐ganciclovir, July 1985‐April 1998), Era 2 (Oral ganciclovir, May 1998‐December 2004), Era 3 (Valganciclovir, January 2005‐December 2015). Survival analysis and Cox regression were performed at 10 years.ResultsA total of 620 heart transplants were included in our analysis; 20% were CMV mismatched pre‐transplant. Thirty‐eight percent of patients were infected with CMV within the first two post‐transplant years. Survival analysis showed D/R CMV serostatus did not significantly impact survival of heart recipients at 10 years (P = 0.11). Survival was significantly different across eras for D−/R+, D+/R+, and D+/R+ (P = 0.043) but not D−/R− patients (P = 0.8). Cox regression revealed that patients transplanted in the valganciclovir era have an estimated 29% reduced risk of death (P = 0.047) compared to patients transplanted in the pre‐ganciclovir era after controlling for age at transplantation, D/R CMV serostatus and CMV infection.ConclusionOur review of the impact of CMV managed differently across eras suggests in heart transplantation there is no influence of D/R CMV serostatus on 10 year survival.
Benign notochordal cell tumour: clinicopathology and molecular profiling of 13 cases
Authors: Du Jiang , Xu Li , Cui Yun , Liu Zhaoxia , Su Yujin , Li Guilin 
Published: October 2018

AimsTo study the clinicopathological and molecular features of benign notochordal cell tumours (BNCTs) and their differential diagnosis from chordoma.Methods13 cases of BNCT were investigated. The genome-wide copy number imbalances were performed using Oncoscan CNV array in three cases and fluorescence in situ hybridisation (FISH) detection of epidermal growth factor receptor (EGFR)/chromosome 7 enumeration probe (CEP7), LSI1p36/1q21, LSI19p13/19q13, CEP3/CEP12 and Telvysion 6 P was performed in 13 cases.ResultsAll 13 BNCTs were symptomatic and eight cases showed a close relationship with the bones of the skull base. The important histological character for differential diagnosis with chordoma was the absence of extracellular matrix and eosinophil cells and the presence of vacuoles in most tumour cells. Immunohistochemical staining of AE1/AE3, vimentin, epithelial membrane antigen, S-100 and brachyury (100% each) were positive in BNCTs. Gain of chromosome 7 occurred in 10 cases (76.9%), gain of 1p in four (30.8%), gain of 1q in five (38.5%), gain of 19p and 19q in five (38.5%), gain of chromosome 12 in 11 cases (84.6%), gain of 6p in eight (61.5%) and gain of chromosome 3 in four cases (30.8%).ConclusionsIn contrast to chordoma, chromosome gain or normal copy number was more common while chromosome loss was infrequent in BNCTs. This may be a differential diagnosis clue for chordoma and may be an important characteristic in the progression of notochordal cell tumours.
Burden of rare variants in causative genes for amyotrophic lateral sclerosis (ALS) accelerates age at onset of ALS
Authors: Naruse Hiroya , Ishiura Hiroyuki , Mitsui Jun , Takahashi Yuji , Matsukawa Takashi , Tanaka Masaki , Doi Koichiro , Yoshimura Jun , Morishita Shinichi , Goto Jun , Toda Tatsushi , Tsuji Shoji 
Published: October 2018

ObjectivesTo evaluate the burden of rare variants in the causative genes for amyotrophic lateral sclerosis (ALS) on the age at onset of ALS in a Japanese case series.MethodsWe conducted whole-exome sequencing analysis of 89 families with familial ALS (FALS) and 410 patients with sporadic ALS (SALS) to identify known pathogenic mutations or rare functionally predicted deleterious variants in the causative genes for ALS. Rare variants (minor allele frequency <1%) with scaled Combined Annotation-Dependent Depletion score >20 were defined as rare functionally predicted deleterious variants. The patients with ALS were classified on the basis of the number of pathogenic and/or rare functionally predicted deleterious variants, and the age at onset was compared among the classified groups.ResultsWhole-exome sequencing analysis revealed known pathogenic mutations or rare functionally predicted deleterious variants in causative genes for ALS in 56 families with FALS (62.9%) and 87 patients with SALS (21.2%). Such variants in multiple genes were identified in seven probands with FALS and eight patients with SALS. The ages at onset in the patients with ALS with multiple variants were significantly earlier than those in other patients with ALS. Even when the patients with known pathogenic mutations were excluded, a significantly earlier onset of the disease was still observed in patients with multiple rare functionally predicted deleterious variants.ConclusionsA substantial number of patients carried rare variants in multiple genes, and the burden of rare variants in the known causative genes for ALS affects the age at onset in the Japanese ALS series.
Effect of childhood pneumococcal conjugate vaccination on invasive disease in older adults of 10 European countries: implications for adult vaccination
Authors: Hanquet Germaine , Krizova Pavla , Valentiner-Branth Palle , Ladhani Shamez N , Nuorti J Pekka , Lepoutre Agnes , Mereckiene Jolita , Knol Mirjam , Winje Brita A , Ciruela Pilar , Ordobas Maria , Guevara Marcela , McDonald Eisin , Morfeldt Eva , Kozakova Jana , Slotved Hans-Christian , Fry Norman K , Rinta-Kokko Hanna , Varon Emmanuelle , Corcoran Mary , van der Ende Arie , Vestrheim Didrik F , Munoz-Almagro Carmen , Latasa Pello , Castilla Jesus , Smith Andrew , Henriques-Normark Birgitta , Whittaker Robert , Pastore Celentano Lucia , Savulescu Camelia 
Published: October 2018

BackgroundPneumococcal conjugate vaccines (PCVs) have the potential to prevent pneumococcal disease through direct and indirect protection. This multicentre European study estimated the indirect effects of 5-year childhood PCV10 and/or PCV13 programmes on invasive pneumococcal disease (IPD) in older adults across 13 sites in 10 European countries, to support decision-making on pneumococcal vaccination policies.MethodsFor each site we calculated IPD incidence rate ratios (IRR) in people aged ≥65 years by serotype for each PCV10/13 year (2011–2015) compared with 2009 (pre-PCV10/13). We calculated pooled IRR and 95% CI using random-effects meta-analysis and PCV10/13 effect as (1 − IRR)*100.ResultsAfter five PCV10/13 years, the incidence of IPD caused by all types, PCV7 and additional PCV13 serotypes declined 9% (95% CI −4% to 19%), 77% (95% CI 67% to 84%) and 38% (95% CI 19% to 53%), respectively, while the incidence of non-PCV13 serotypes increased 63% (95% CI 39% to 91%). The incidence of serotypes included in PCV13 and not in PCV10 decreased 37% (95% CI 22% to 50%) in six PCV13 sites and increased by 50% (95% CI −8% to 146%) in the four sites using PCV10 (alone or with PCV13). In 2015, PCV13 serotypes represented 20–29% and 32–53% of IPD cases in PCV13 and PCV10 sites, respectively.ConclusionOverall IPD incidence in older adults decreased moderately after five childhood PCV10/13 years in 13 European sites. Large declines in PCV10/13 serotype IPD, due to the indirect effect of childhood vaccination, were countered by increases in non-PCV13 IPD, but these declines varied according to the childhood vaccine used. Decision-making on pneumococcal vaccination for older adults must consider the indirect effects of childhood PCV programmes. Sustained monitoring of IPD epidemiology is imperative.
Evaluation of the Georgia trauma system using the American College of Surgeons Needs Based Assessment of Trauma Systems tool
Authors: Ashley Dennis W , Pracht Etienne E , Garlow Laura E , Medeiros Regina S , Atkins Elizabeth V , Johns Tracy J , Ferdinand Colville H , Dente Christopher J , Dunne James R , Nicholas Jeffrey M 
Published: October 2018

BackgroundThe American College of Surgeons Needs Based Assessment of Trauma Systems (NBATS) tool was developed to help determine the optimal regional distribution of designated trauma centers (DTC). The objectives of our current study were to compare the current distribution of DTCs in Georgia with the recommended allocation as calculated by the NBATS tool and to see if the NBATS tool identified similar areas of need as defined by our previous analysis using the International Classification of Diseases, Ninth Revision, Clinical Modification Injury Severity Score (ICISS).MethodsPopulation counts were acquired from US Census publications. Transportation times were estimated using digitized roadmaps and patient zip codes. The number of severely injured patients was obtained from the Georgia Discharge Data System for 2010 to 2014. Severely injured patients were identified using two measures: ICISS<0.85 and Injury Severity Score >15.ResultsThe Georgia trauma system includes 19 level I, II, or III adult DTCs. The NBATS guidelines recommend 21; however, the distribution differs from what exists in the state. The existing DTCs exactly matched the NBATS recommended number of level I, II, or III DTCs in 2 of 10 trauma service areas (TSAs), exceeded the number recommended in 3 of 10 TSAs, and was below the number recommended in 5 of 10 TSAs. Densely populated, or urban, areas tend to be associated with a higher number of existing centers compared with the NBATS recommendation. Other less densely populated TSAs are characterized by large rural expanses with a single urban core where a DTC is located. The identified areas of need were similar to the ones identified in the previous gap analysis of the state using the ICISS methodology.DiscussionThe tool appears to underestimate the number of centers needed in extensive and densely populated areas, but recommends additional centers in geographically expansive rural areas. The tool signifies a preliminary step in assessing the need for state-wide inpatient trauma center services.Level of evidenceEconomic, level IV.
Banning open carry of unloaded handguns decreases firearm-related fatalities and hospital utilization
Authors: Callcut Rachael A , Robles Anamaria M Joyce , Mell Matthew W 
Published: October 2018

BackgroundSince 1967, in California it has been illegal to openly carry a loaded firearm in public except when engaged in hunting or law enforcement. However, beginning January 1, 2012, public open carry of unloaded handguns also became illegal. Fatal and non-fatal (NF) firearm injuries were examined before and after adoption of the 2012 ban to quantify the effect of the new law on public health.MethodsState-level data were obtained directly from California and nine other US state inpatient and emergency department (ED) discharge databases, and the Centers for Disease Control Web-Based Injury Statistics Query and Reporting System. Case numbers of firearm fatalities, NF hospitalizations, NF ED visits, and state-level population estimates were extracted. Each incident was classified as unintentional, self-inflicted, or assault. Crude incidence rates were calculated. The strength of gun laws was quantified using the Brady grade. There were no changes to open carry in these nine states during the study. Using a difference-in-difference technique, the rate trends 3 years preban and postban were compared.ResultsThe 2012 open carry ban resulted in a significantly lower incident rate of both firearm-related fatalities and NF hospitalizations (p<0.001). The effect of the law remained significant when controlling for baseline state gun laws (p<0.001). Firearm incident rate drops in California were significant for male homicide (p=0.023), hospitalization for NF assault (p=0.021  male; p=0.025 female), and ED NF assault visits (p=0.04). No significant decreases were observed by sex for suicides or unintentional injury. Changing the law saved an estimated 337 lives (3.6% fewer deaths) and 1285 NF visits in California during the postban period.DiscussionOpen carry ban decreases fatalities and healthcare utilization even in a state with baseline strict gun laws. The most significant impact is from decreasing firearm-related fatal and NF assaults.Level of evidenceIII, epidemiology.
Influence of previous medical treatments on social rank in dairy cows
Authors: Littooij Anne , Butterworth Andrew 
Published: October 2018

Animal health can present economic and animal welfare concerns for dairy farmers. However, it is unknown whether changes in behaviour as a result of sickness have long‐term effects, and whether there is a relationship between the social rank of cows in the herd at a moment in time and the medical treatment history of these cows. The behaviour of 100 high‐yielding cows in the waiting area (collecting yard) before the milking parlour was studied for five milking sessions to assess the interactions between the cows, as the cows waited to be milked. The cows were filmed, and the interactions between cows were recorded using an ethogram. The summated social rank score of each cow was compared with its medical treatment history. In our analysis, a positive relationship was found between medical treatment history and social rank, however this association was discounted when age was accounted for. When a subsample of cows older than 4.0 years was analysed to examine the relationship between social rank and medical treatment history in older cows, no significant correlation existed. These results suggest that the relationship between social rank and medical treatment history identified in the analysis is predominately an effect of age. This finding is contradictory to the hypothesis that ‘a higher historical level of medical treatments, and the disruption and setbacks associated with these disease conditions, would result in a lower position in the social rank.’ This preliminary study reports the findings from one particular herd, and across one relatively short time span, and because associations between treatment history and behaviour may be of interest in management decisions for producers, it is recommended that further investigation of this subject is carried out.
Application of genetic algorithm in M × N reconfigurable antenna array based on RF MEMS switches
Authors: Tian Wenchao , Wu Daowei , Chao Qiang , Chen Zhiqiang , Wang Yongkun 
Published: October 2018

With the continuous development of the wireless communication, a device needs to integrate multiple antennas, which will lead to increased volume, increased cost, electromagnetic compatibility problems and increased weight. This paper presents a [Formula: see text] reconfigurable antenna array based on RF MEMS switches. The modeling script of [Formula: see text] reconfigurable antenna array is written in MATLAB by using MATLAB-HFSS-API. In order to quickly get a switch array with target frequency, genetic algorithm is applied to [Formula: see text] reconfigurable antenna array. Taking the [Formula: see text] reconfigurable antenna array as an example, a switch array with the resonant frequency of 3.81 GHz is searched from its 4096 switch arrays. The switch array found by genetic algorithm is 1 1 0 0 1 0 0 1 1 0 1 0. The resonant frequency and S11 parameter of this switch array is 3.81 GHz and −20.96 dB. The search takes 6.77 h and the efficiency is 17 times of the simulating all switch arrays.
Gangdese magmatism in southern Tibet and India–Asia convergence since 120 Ma
Authors: Zhu Di-Cheng , Wang Qing , Chung Sun-Lin , Cawood Peter A. , Zhao Zhi-Dan 
Published: October 2018

Abstract

A compilation of 290 zircon U–Pb ages of intrusive rocks indicates that the Gangdese Batholith in southern Tibet was emplaced from
c.
210 Ma to
c.
10 Ma. Two intense magmatic pulses within the batholith occur at: (1) 90 ± 5 Ma, which is restricted to 89–94° E in the eastern segment of the southern Lhasa subterrane; and (2) 50 ± 3 Ma, which is widespread across the entire southern Lhasa subterrane. The latter pulse was followed by a phase of widespread but volumetrically small, dominantly felsic adakitic intrusive rocks at 16 ± 2 Ma. The Linzizong volcanism in the Linzhou Basin was active from 60.2 to 52.3 Ma, rather than 69–44 Ma as previously estimated. During 120–75 Ma, Gangdese Batholith magmatism migrated from south to north, arguing against rollback of the downgoing, north-dipping Neo-Tethyan oceanic lithosphere for the generation of the 90 ± 5 Ma magmatic pulse. Petrological, geochemical and metamorphic data indicate that this pulse was likely to have been generated through subduction of the Neo-Tethyan oceanic ridge lithosphere. Subsequent Gangdese Batholith magmatism propagated both south and north during 70–45 Ma, and finally concentrated at the southern margin of the Lhasa Terrane at 45–30 Ma. The enhanced mafic magmatism since
c.
70 Ma, magmatic flare-up with compositional diversity at
c.
51 Ma and increased magmatic temperature at 52–50 Ma are interpreted as the consequences of slab rollback from
c.
70 Ma and slab breakoff of the Neo-Tethyan oceanic lithosphere that began at
c.
53 Ma. The India–Asia convergence was driven by Neo-Tethyan subduction with a normal rate of convergence at 120–95 Ma, ridge subduction at 95–85 Ma, then subduction of a young and buoyant oceanic lithosphere after ridge subduction with rate deceleration at 84–67 Ma, Deccan plume activity and slab rollback with rate acceleration at 67–51 Ma, slab breakoff for sudden drop of the convergence rate at
c.
51 Ma, and finally the descent of the high-density Indian continental lithosphere beneath Asia since
c.
50 Ma.