bluuebunny/crossref_metadata_2025 huggingface dataset:
Modified two‐dimensional response as surrogate marker of overall survival in patients with metastatic colorectal cancer
Authors: Nakayama Goro , Fujii Tsutomu , Murotani Kenta , Uehara Keisuke , Hattori Norifumi , Hayashi Masamichi , Tanaka Chie , Kobayashi Daisuke , Kanda Mitsuro , Yamada Suguru , Sugimoto Hiroyuki , Koike Masahiko , Fujiwara Michitaka , Ando Yuichi , Kodera Yasuhiro
Published: August 2016

The identification of surrogate markers for long‐term outcomes in patients with metastatic colorectal cancer (mCRC) may help in designing treatment regimens. The aim of this study was to assess whether two‐dimensional response (2‐DR) can serve as a new surrogate marker for overall survival (OS) in patients with mCRC. The study group consisted of 99 patients with mCRC from two independent cohorts who were treated with oxaliplatin‐based chemotherapy plus bevacizumab. Two‐dimensional response was defined as an area enclosed by coordinate points, including early tumor shrinkage at 8 weeks, depth of response at nadir, and 20% increase over nadir at progression. Each variable was weighted by its contribution rate to OS. The model was developed and internally validated in the learning cohort, and the performance of this model was externally verified in the validation cohort. Spearman correlation coefficients for 2‐DR and OS in the learning and validation cohorts were 0.593 and 0.661, respectively. The C‐indexes in predicting OS were 0.724 (95% confidence interval, 0.623–0.815) in the learning cohort and 0.762 (95% confidence interval, 0.651–0.873) in the validation cohort. Overall survival was significantly longer in patients with high 2‐DR values than in patients with low 2‐DR values in both the learning (37.0 vs. 24.1 months, P < 0.001) and validation (41.2 vs. 20.4 months, P < 0.001) cohorts. In contrast, differences in early tumor shrinkage and depth of response were not statistically significant. Multivariate analyses showed that 2‐DR was an independent prognostic factor for OS.
Social participation of teenagers and young adults with developmental co‐ordination disorder and strategies that could help them: results from a scoping review
Authors: Gagnon‐Roy M. , Jasmin E. , Camden C.
Published: August 2016

Background

The impact of developmental co‐ordination disorder (DCD) on teenagers' and young adults' participation is not well documented. This article aims to synthesize the current knowledge on social participation, which is the performance of an individual in realizing his or her daily activities and social roles within its life environment. Strategies and interventions to support youths (15–25 years old) with DCD were also synthesized.

Methods

A scoping review interrogating three databases and using ‘snowballing techniques’ was performed to identify both scientific and grey literature published between 2004 and 2014. Over 1000 documents were screened and 57 were read in full; 28 met inclusion criteria. A charting form based on 12 life habits described in the disability creation process and developed by two reviewers was used to extract data and report the results.

Results

All life habits were reported to be affected for teenagers and young adults with DCD, with education and interpersonal relationships being the most frequently discussed. During adolescence and adulthood, new tasks and subsequent difficulties emerge, such as driving. Mental health difficulties emerged as a key theme. Few strategies and interventions were described to support social participation of youths with DCD.

Conclusion

Many life habits are challenging for youths with DCD, but few evidence‐based strategies and interventions have been designed to help them to increase their social participation.
The effectiveness of taping on children with cerebral palsy: a systematic review
Authors: Güçhan Zehra , Mutlu Akmer
Published: August 2016

Aim

Taping is popular in a variety of paediatric clinical settings. The purpose of this study was to investigate the effectiveness of taping on the rehabilitation of children with cerebral palsy (CP).

Method

We used MEDLINE, Embase, PubMed, CINAHL, and the Cochrane Central Register of Controlled Trials as the electronic databases for the review. We reviewed all relevant studies published up to May 2015. We also analysed pertinent secondary references. We used Sackett's Levels of Evidence and the guidelines for critical review of McMaster University to criticize the reviewed articles.

Results

Nine papers met the inclusion criteria. Five of these were randomized controlled trials, three were case series, and one was a single case study. Four papers were high quality according to the methodological critical forms of this review, and two of these found that taping was effective in increasing activity in children with CP.

Interpretation

Although benefits of taping were found in the population, and functional gains according to the International Classification of Functioning, Disability and Health were obtained, the evidence was not conclusive. Randomized controlled trials with larger sample sizes and with more specific taping procedures are required to strengthen the evidence for the effectiveness of taping on children with CP.
Insufficient global health education in European neurological post‐graduate training: a European Association of Young Neurologists and Trainees survey
Authors: Sauerbier A. , Macerollo A. , Györfi O. , Balicza P. , Moarcas M. , Papp V. , Zis P. , Klingelhoefer L. , Saifee T. , Struhal W. , Sellner J.
Published: August 2016

Background and purpose

The awareness of and demand for neurological expertise in global health (GH) have emerged over recent years and have become more relevant due to the increasing numbers of refugees from developing countries arriving in Europe. This study aimed to assess the provision of GH education and opportunities for international exchange during neurology post‐graduate training with a focus on Europe.

Methods

We developed a questionnaire covering different aspects of and interest in GH education on behalf of the European Association of Young Neurologists and Trainees. Residents in neurology and junior neurologists (RJN) were approached to complete this survey.

Results

Completed questionnaires were returned by 131 RJNs, of whom 65.7% were women and 84.0% were between 26 and 35 years old. In total, almost one‐third (29.0%) of RJNs reported that their residency programs offered training in GH. Limited education was reported for women's or children's health and neurological disorders of immigrants and refugees, as only 22.1%, 25.2% and 22.1% of RJNs reported that such training was offered, respectively. The curriculum rarely included coverage of the global impact of neurological disorders. Definite plans to volunteer in a developing country were reported by 7.6%. The majority of the participants acknowledged the importance of GH training and international exchange during post‐graduate education.

Conclusion

This survey corroborates the interest in and appreciation of GH education by European RJNs. However, there are shortcomings in training and opportunities for international exchange. Academic neurology and international bodies, including the European Academy of Neurology, are requested to address this.
Life's utilization of B vitamins on early Earth
Authors: Monteverde D. R. , Gómez‐Consarnau L. , Suffridge C. , Sañudo‐Wilhelmy S. A.
Published: August 2016

Coenzymes are essential across all domains of life. B vitamins (B1‐thiamin, B2‐riboflavin, B3‐niacin, B5‐pantothenate, B6‐pyridoxine, B7‐biotin, and B12‐cobalamin) represent the largest class of coenzymes, which participate in a diverse set of reactions including C1‐rearrangements, DNA repair, electron transfer, and fatty acid synthesis. B vitamin structures range from simple to complex heterocycles, yet, despite this complexity, multiple lines of evidence exist for their ancient origins including abiotic synthesis under putative early Earth conditions and/or meteorite transport. Thus, some of these critical coenzymes likely preceded life on Earth. Some modern organisms can synthesize their own B vitamins de novo while others must either scavenge them from the environment or establish a symbiotic relationship with a B vitamin producer. B vitamin requirements are widespread in some of the most ancient metabolisms including all six carbon fixation pathways, sulfate reduction, sulfur disproportionation, methanogenesis, acetogenesis, and photosynthesis. Understanding modern metabolic B vitamin requirements is critical for understanding the evolutionary conditions of ancient metabolisms as well as the biogeochemical cycling of critical elements such as S, C, and O.
Effect of resistance training on liver fat and visceral adiposity in adults with obesity: A randomized controlled trial
Authors: Keating Shelley E. , Hackett Daniel A. , Parker Helen M. , Way Kimberley L. , O'Connor Helen T. , Sainsbury Amanda , Baker Michael K. , Chuter Vivienne H. , Caterson Ian D. , George Jacob , Johnson Nathan A.
Published: August 2016

Aim

Regular aerobic exercise reduces visceral adipose tissue (VAT) and liver fat, however, not all individuals are able to adopt and adhere to such programs. Progressive resistance training (PRT) may be an alternative therapy, but there is limited available evidence. We examined the efficacy of PRT as per current exercise guidelines, compared with sham exercise placebo on liver fat and VAT.

Methods

Twenty‐nine inactive and overweight/obese (body mass index ≥25 kg/m2) adults (age 29–59) were randomized to receive 8 weeks of PRT (n = 15, 10 exercises per session, 8–12 repetitions, 2–3 sets per exercise at 80–85% of one‐repetition maximum, 3 days per week) or a sham exercise placebo control (CON) (n = 14). Change in liver fat, VAT, and abdominal s.c. adipose tissue (SAT) were assessed by magnetic resonance spectroscopy and imaging).

Results

There were no significant group by time interactions for change in liver fat in PRT versus CON groups (−0.07 ± 0.31% vs. 0.55 ± 0.77%, respectively, P = 0.19), VAT (−175 ± 85 cm3 vs. 10 ± 64 cm3, respectively, P = 0.11), or abdominal SAT (−436 ± 245 cm3 vs. 127.29 ± 182 cm3, respectively, P = 0.10) despite a significant increase in muscle volume (55 ± 78 cm3 vs. −0.04 ± 8 cm3, respectively, P = 0.03).

Conclusion

Traditional PRT is not effective for reducing liver fat in overweight/obese adults compared with placebo control. Although PRT has known metabolic benefits, an adequate volume of aerobic exercise should be promoted if liver fat is the therapeutic target.
Beneficial effect of arterial embolization with warmed miriplatin for multiple hepatocellular carcinoma
Authors: Ikeda Kenji , Kawamura Yusuke , Kobayashi Masahiro , Fujiyama Shunichiro , Sezaki Hitomi , Hosaka Tetsuya , Akuta Norio , Saitoh Satoshi , Suzuki Fumitaka , Suzuki Yoshiyuki , Arase Yasuji , Kumada Hiromitsu
Published: August 2016

Aim

The effect of transcatheter arterial chemoembolization (TACE) is not necessarily sufficient in patients with multiple hepatocellular carcinoma (HCC). We evaluated the antitumor activity and adverse events of TACE using warmed miriplatin suspension for multiple HCC.

Methods

Seventy patients with multiple HCC received TACE using warmed miriplatin/lipiodol suspension, including patients who were TACE‐naïve (group A, n = 5), those undergoing initial TACE after radical therapies (group B, n = 31), and those with a history of repeated TACE (group C, n = 34). Median tumor size was 19.5 mm and a median of four nodules.

Results

Complete necrosis (TE 4) and partial necrosis (TE 3) of 50% or more were attained in 24 and 19 patients at 3 months after TACE, respectively. Response rates (TE 4 + TE 3) were 60.0% in group A, 83.9% in group B, and 41.2% in group C (P = 0.038). Survival rates of all patients after TACE were 82.6% after 1 year, 65.6% after 2 years, and 47.7% after 3 years. Three‐year survival rates of patients in groups A, B, and C were 53.3%, 78.8%, and 29.7%, respectively (P = 0.0029).

Conclusion

Transcatheter arterial chemoembolization using warmed miriplatin induced high response rate in multiple HCC, and the rate was significantly high in those patients with recurrent multiple HCCs after curative therapies.
The late‐presenting HIV‐infected patient 30 years after the introduction of HIV testing: spectrum of opportunistic diseases and missed opportunities for early diagnosis
Authors: Tominski D , Katchanov J , Driesch D , Daley MB , Liedtke A , Schneider A , Slevogt H , Arastéh K , Stocker H
Published: August 2016

Objectives

The aim of the study was to describe the characteristics of HIV‐infected late presenters, opportunistic diseases at diagnosis and missed opportunities to diagnose HIV infection earlier.

Methods

In a retrospective cohort study, we reviewed the medical records of all adults with newly diagnosed HIV infection admitted to the Department of Infectious Diseases of the Vivantes Auguste‐Viktoria Hospital, Berlin, Germany.

Results

In the 5‐year period from 2009 to 2013, 270 late presenters were identified. The most common AIDS‐defining conditions were oesophageal candidiasis (n = 136; 51%), wasting syndrome (n = 106; 40%) and pneumocystis pneumonia (n = 91; 34%). Fifty‐five patients (21%) had presented with at least one HIV indicator condition on prior contact with health care services without being offered testing for HIV. Female patients and heterosexual men [not men who have sex with men (‘non‐MSM’)] had a significantly higher chance of being among patients previously presenting with indicator conditions and not being tested [odds ratio (OR) 4.7; 95% confidence interval (CI) 2.2–10.0; P < 0.001; and OR 2.4; 95% CI 1.2–5.1; P < 0.01, respectively]. The most commonly missed indicator conditions were leucocytopenia (n = 13; 24%), thrombocytopenia (n = 12; 22%), oral candidiasis (n = 9; 16%), unexplained weight loss (n = 7; 13%), herpes zoster (n = 5; 9%) and cervical dysplasia/cancer (n = 4; 20% of women). The median time between presentation with an indicator condition and the diagnosis of HIV infection was 158.5 days [interquartile range (IQR) 40–572 days]. Patients with oral candidiasis and unexplained weight loss had the shortest time between the “missed opportunity” and the diagnosis of HIV infection. Fifty‐five hospital admissions with a total cost of over EUR 500 000 and – most importantly – six in‐hospital deaths might have been prevented if HIV testing had been performed in patients with documented indicator conditions.

Conclusions

Indicator conditions are still missed by clinicians. Women and ‘non‐MSM’ are at highest risk of presenting with an indicator condition but not being tested for HIV infection.
Nurse‐led hepatocellular carcinoma surveillance clinic provides an effective method of monitoring patients with cirrhosis
Authors: Nazareth Saroj , Leembruggen Nadine , Tuma Rhoda , Chen Sook‐Ling , Rao Samarth , Kontorinis Nick , Cheng Wendy
Published: August 2016

The aim of this study is to examine the acceptability and effectiveness of a nurse‐led hepatocellular carcinoma (HCC) surveillance clinic in high‐risk patients with cirrhosis/advanced fibrosis. Early detection of HCC is associated with better treatment outcomes and improved survival. International guidelines recommend 6‐monthly surveillance of patients at risk of developing HCC. A nurse‐led HCC surveillance protocol was established to support patients in adherence to surveillance protocols. The design used was retrospective document analysis. Retrospective analysis of healthcare records of patients referred to the clinic between August 2009 and December 2015. Extracted data included attendance of clinic visits, blood testing, ultrasound or other imaging, and outcomes. Ultrasound was attended within 6 months in 30.3% of cases and within 7 months in 71.2% of cases. The median time between Nurse‐Led Clinic appointments, ultrasound scans and blood testing did not exceed 9 months. First year FibroScans were attended by 82.9% (63/76) patients; endoscopy was indicated for 42 and attended by 35 (83.3%) patients. Lesions were identified in 16 patients (21.5%) and HCC diagnosed in two patients. One patient died because of HCC and one to sub‐dural haematoma. Nurse‐led HCC surveillance was an effective method of monitoring patients with cirrhosis at high risk of developing HCC. Well‐defined protocols enable timely identification of patients with HCC or hepatic decompensation so that management strategies can be implemented without delay. The potential benefits identified by this study warrant further, rigorous evaluation.
Six central features of the Chinese labour market: A literature survey
Authors: SONG Yang
Published: August 2016

In this comprehensive analytical overview, the author pays particular attention to the changing structure of China's employment towards more private‐sector jobs in urban areas; its rising wages and widening earnings inequality; the persistence of its hukou system, causing labour market discrimination, an urban labour shortage and a rural labour surplus; its more market‐oriented wage structure, albeit with segmentation between firm ownership types; its relatively low unemployment; and the relatively weak role of its traditional labour market institutions, including minimum wages and trade unions. The aim is to contribute to the development of more suitable, China‐specific theoretical models and sound policy analysis.
Microarray‐based annotation of the gut transcriptome of the migratory locust, Locusta migratoria
Authors: Spit J. , Badisco L. , Vergauwen L. , Knapen D. , Vanden Broeck J.
Published: August 2016

The migratory locust, Locusta migratoria, is a serious agricultural pest and important insect model in the study of insect digestion and feeding behaviour. The gut is one of the primary interfaces between the insect and its environment. Nevertheless, knowledge on the gut transcriptome of L. migratoria is still very limited. Here, 48 802 expressed sequence tags were extracted from publicly available databases and their expression in larval gut and/or brain tissue was determined using microarray hybridization. Our data show 2765 transcripts predominantly or exclusively expressed in the gut. Many transcripts had putative functions closely related to the physiological functions of the gut as a muscular digestive organ and as the first barrier against microorganisms and a wide range of toxins. By means of a ranking procedure based on the relative signal intensity, we estimated 15% of the transcripts to show high expression levels, the highest belonging to diverse digestive enzymes and muscle‐related proteins. We also found evidence for very high expression of an allergen protein, which could have important implications, as locusts form a traditional food source in various parts of the world, and were also recently added to the list of insects fit for human consumption in Europe. Interestingly, many highly expressed sequences have as yet unknown functions. Taken together, the present data provide significant insight into locust larval gut physiology, and will be valuable for future studies on the insect gut.
T‐cell metabolism governing activation, proliferation and differentiation; a modular view
Authors: Dimeloe Sarah , Burgener Anne‐Valérie , Grählert Jasmin , Hess Christoph
Published: August 2016

T lymphocytes are a critical component of the adaptive immune system mediating protection against infection and malignancy, but also implicated in many immune pathologies. Upon recognition of specific antigens T cells clonally expand, traffic to inflamed sites and acquire effector functions, such as the capacity to kill infected and malignantly transformed cells and secrete cytokines to coordinate the immune response. These processes have significant bioenergetic and biosynthetic demands, which are met by dynamic changes in T‐cell metabolism, specifically increases in glucose uptake and metabolism; mitochondrial function; amino acid uptake, and cholesterol and lipid synthesis. These metabolic changes are coordinate by key cellular kinases and transcription factors. Dysregulated T‐cell metabolism is associated with impaired immunity in chronic infection and cancer and conversely with excessive T‐cell activity in autoimmune and inflammatory pathologies. Here we review the key aspects of T‐cell metabolism relevant to their immune function, and discuss evidence for the potential to therapeutically modulate T‐cell metabolism in disease.
Factors influencing the inclusion of oral health education in individualized education plans of children with autism spectrum disorders in Singapore
Authors: Tong Huei Jinn , Lee Hei Yi , Lee Ying Ting , Low Yuxuan , Lim Cassandra Ruiqi , Nair Rahul
Published: August 2016

Background

Prevention of oral diseases in children with autism spectrum disorder (ASD) is possible via incorporation of oral health education (OHE) into individualized education plans.

Objectives

To assess (i) whether training can improve teachers’ oral heath knowledge, (ii) whether OHE is taught to children with ASD, and (iii) factors associated with teachers’ perceived barriers to the implementation of OHE.

Design

Teachers working in special schools were recruited. Two pre‐tested questionnaires were administered, before and after a training session. The effectiveness of the intervention was evaluated. Teachers were also surveyed on their teaching of caries prevention and perceived barriers of teaching OHE.

Results

There was a significant increase in knowledge scores post‐intervention (P < 0.001). Teachers were more likely to incorporate OHE into their teaching if trained by dental professionals (P = 0.022) and provided teaching materials (P = 0.001). Teachers’ level of baseline OHE knowledge was a predictor and significantly negatively associated with levels of perceived overall and personal barriers (both P < 0.001).

Conclusion

OHE is included in the curriculum of the schools surveyed, but this is very limited. The training programme increased teachers’ oral health knowledge competence scores. Levels of knowledge, lack of training, and teaching materials are barriers to incorporating OHE in their teaching curriculum.
California Commits $5m for Gun Violence Research
Authors: Tarran Brian
Published: August 2016

After a 20-year federal funding freeze, state legislators take steps to develop evidence base for “prevention policies and programs”
Phylogeography of Quercus aquifolioides provides novel insights into the Neogene history of a major global hotspot of plant diversity in south‐west China
Authors: Du Fang K. , Hou Meng , Wang Wenting , Mao Kangshan , Hampe Arndt
Published: August 2016

Aim

Hotspots of biodiversity are often associated with areas that have undergone orogenic activity during recent geological history. Mountain uplifts are known to catalyse species radiation but their impact on evolutionarily stable taxa such as many trees remains little understood. The oak Quercus aquifolioides is endemic to yet widely distributed across the Hengduanshan Biodiversity Hotspot in the Eastern Himalayas. Here, we investigate how the region's Neogene and Quaternary history has driven the species' past population dynamics and the resulting extant patterns of intraspecific diversity.

Location

Hengduanshan Biodiversity Hotspot in SW China.

Methods

We sampled 58 populations throughout the species range and genotyped a total of 959 individuals at four chloroplast DNA fragments and 11 nuclear microsatellite loci. Phylogenetic reconstructions, molecular dating techniques and ancestral area reconstructions were used in combination with population genetic statistics to infer the biogeographical history of Q. aquifolioides. The phylogeographical study was complemented by a survey of fossil records and a niche modelling exercise.

Results

Combined molecular and fossil evidence indicates that Q. aquifolioides descended during the late Miocene from the central Qinghai‐Tibet Plateau into Tibet and the western Sichuan Plateau, and from there, into the area of highest endemism in the Hengduan Mountains sensu lato. Great apparent population stability and a haplotype ‘radiation’ in this area contrasted with marked extinction–recolonization dynamics and reduced population diversity in Tibet. We found evidence for extremely limited seed gene flow but extensive pollen gene flow (global FST: cpDNA = 0.98, nSSR = 0.07) with signals of asymmetric pollen dispersal from the Hengduan Mountains into Tibet.

Main conclusion

Our results provide insights of unprecedented detail into the ancient biogeographical history of the Hengduanshan Biodiversity Hotspot, suggesting that past environmental changes in the region may have catalysed radiative diversifications within species much in the same way as among species.
Flexible Austerity and Supranational Autonomy. The Reformed Excessive Deficit Procedure and the Asymmetry between Liberalization and Social Regulation in the EU
Authors: Seikel Daniel
Published: August 2016

This paper analyzes how the apparently merely technical introduction of reversed qualified majority voting for the excessive deficit procedure included in the Six Pack and the Fiscal Compact shifts not only the institutional balance between the European Commission and the Member States but also the relationship between liberalization and social regulation in the EU. In bringing together institutional analysis and a political economy perspective, the paper shows how the strengthening of the Commission's discretionary decision‐making authority in a context of intergovernmental power imbalances between debtor and creditor states extends the asymmetry between market‐making and market‐correction to the area of political decision‐making. In consequence, economic and social policies are subordinated to the primacy of austerity.
Ocean floor and subduction record in the Zermatt‐Saas rodingites, Valtournanche, Western Alps
Authors: Zanoni D. , Rebay G. , Spalla M. I.
Published: August 2016

Multiscale structural analysis and petrological modelling were used to establish the pressure‐peak mineral assemblages and pressure–temperature (P–T) conditions recorded in the rodingites of the upper Valtournanche portion of the oceanic Zermatt‐Saas Zone (ZSZ; Western Alps, northwestern Italy) during Alpine subduction. Rodingites occur in the form of deformed dykes and boudins within the hosting serpentinites. A field structural analysis showed that rodingites and serpentinites record four ductile deformation stages (D1–D4) during the Alpine cycle, with the first three stages associated with new foliations. The most pervasive fabric is S2 that is marked by mineral assemblages in serpentinite indicating pressure‐peak conditions, involving mostly serpentine, clinopyroxene, olivine, Ti‐clinohumite and chlorite. Three rodingite types can be defined: epidote‐bearing, garnet–chlorite–clinopyroxene‐bearing and vesuvianite‐bearing rodingite. In these, the pressure‐peak assemblages coeval with S2 development involve: (i) epidoteII + clinopyroxeneII + Mg‐chloriteII + garnetII ± rutile ± tremoliteI in the epidote‐bearing rodingite; (ii) Mg‐chloriteII + garnetII clinopyroxeneII ± vesuvianiteII ± ilmenite in the garnet–chlorite–clinopyroxene‐bearing rodingite; (iii) vesuvianiteII + Mg‐chloriteII + clinopyroxeneII + garnetII ± rutile ± epidote in vesuvianite‐bearing rodingite. Despite the pervasive structural reworking of the rodingites during Alpine subduction, the mineral relicts of the pre‐Alpine ocean floor history have been preserved and consist of clinopyroxene porphyroclasts (probable igneous relicts from gabbro dykes) and Cr‐rich garnet and vesuvianite (relicts of ocean floor metasomatism). Petrological modelling using thermocalc in the NCFMASHTO system was used to constrain the P–T conditions of the S2 mineral assemblages. The inferred values of 2.3–2.8 GPa and 580–660 °C are consistent with those obtained for syn‐S2 assemblages in the surrounding serpentinites. Multiscale structural analysis indicates that some ocean floor minerals remained stable under eclogite facies conditions suggesting that minerals such as vesuvianite, which is generally regarded as a low‐P phase, could also be stable in favourable chemical systems under high‐P/ultra‐high‐pressure (HP/UHP) conditions. Finally, the reconstructed P–T–d–t path indicates that the P/T ratio characterizing the D2 stage is consistent with cold subduction as estimated in this part of the Alps. The estimated pressure‐peak values are higher than those previously reported in this part of ZSZ, suggesting that the UHP units are larger and/or more abundant than those previously suggested.
Dynamic expression of the mouse orthologue of the human amyotropic lateral sclerosis associated gene C9orf72 during central nervous system development and neuronal differentiation
Authors: Ferguson Ross , Serafeimidou‐Pouliou Eleni , Subramanian Vasanta
Published: August 2016

The hexanucleotide repeat in the first intron of the C9orf72 gene is the most significant cause of amyotropic lateral sclerosis as well as some forms of fronto‐temporal dementia. The C9orf72 protein has been previously reported to be expressed in post‐mortem human brain as well as in late embryonic and some postnatal stages in mice. Herein, we present a detailed study of the distribution of C9orf72 protein in the embryonic, postnatal and adult mouse brain, spinal cord as well as during the differentiation of P19 embryonal carcinoma cells to neurons including motor neurons. We show that the expression levels of the C9orf72 transcripts in the developing and adult mouse brain as well as in differentiating neurons, are dynamic. Besides the strong expression in the cerebellum and motor cortex reported previously, we show for the first time that C9orf72 is expressed strongly in the olfactory bulb and also in the hippocampus. Our immunostaining data also reveal a hitherto unreported switch in the cellular distribution of C9orf72 from a predominantly cytoplasmic to a nucleo‐cytoplasmic distribution during corticogenesis. This switch in distribution was also observed during differentiation of the pluripotent embryonal carcinoma P19 cell line to mature neurons. Our findings have implications for interpreting the pathophysiology caused by the repeat expansions in C9orf72 in mouse models.
The use of volunteers to help older medical patients mobilise in hospital: a systematic review
Authors: Baczynska Alicja M , Lim Stephen ER , Sayer Avan A , Roberts Helen C
Published: August 2016

Aims and objectives

To review current evidence for the use of volunteers to mobilise older acute medical in‐patients.

Background

Immobility in hospital is associated with poor healthcare outcomes in older people, but maintaining mobility is frequently compromised due to time pressures experienced by clinical staff. Volunteers are established in many hospitals, usually involved in indirect patient care. Recent evidence suggests that trained mealtime volunteers had a positive impact on patients and hospital staff. It is unclear whether volunteers can help older inpatients to mobilise.

Design

Systematic review.

Methods

We searched Cochrane, Medline, Embase, CINAHL, AMED and Google databases using MeSH headings and keywords within six key themes: inpatients, older, mobility/exercise, delirium, falls and volunteers. Full texts of relevant articles were retrieved and reference lists reviewed.

Results

Of the 2428 articles that were identified, two scientific studies and three reports on quality improvement initiatives were included in the final review. One study included volunteer assisted mobilisation as part of a delirium prevention intervention (HELP). The second study has not reported yet (MOVE ON). The contribution of volunteers in both is unclear. Three quality improvement initiatives trained volunteers to help mobilise patients. They were not formally evaluated but report positive effects of the volunteers on patient and staff satisfaction.

Conclusions

This review has identified a lack of scientific evidence for the use of volunteers in mobilising older medical inpatients, but quality improvement initiatives suggest that volunteers can be employed in this role with reports of staff and patient satisfaction: this is an area for further development and evaluation.

Relevance to clinical practice

This review outlines the evidence for the involvement of volunteers in maintaining patients’ mobility, identifies mobilisation protocols that have been used, the need to train volunteers and for formal evaluation of volunteers in this role. Prospero registration number: CRD42014010388.
Pharmacokinetic profiles of the active metamizole metabolites in healthy horses
Authors: Giorgi M. , Aupanun S. , Lee H.‐K. , Poapolathep A. , Rychshanova R. , Vullo C. , Faillace V. , Laus F.
Published: August 2016

Metamizole (MT) is an analgesic and antipyretic drug labelled for use in humans, horses, cattle, swine and dogs. MT is rapidly hydrolysed to the active primary metabolite 4‐methylaminoantipyrine (MAA). MAA is formed in much larger amounts compared with other minor metabolites. Among the other secondary metabolites, 4‐aminoantipyrine (AA) is also relatively active. The aim of this research was to evaluate the pharmacokinetic profiles of MAA and AA after dose of 25 mg/kg MT by intravenous (i.v.) and intramuscular (i.m.) routes in healthy horses. Six horses were randomly allocated to two equally sized treatment groups according to a 2 × 2 crossover study design. Blood was collected at predetermined times within 24 h, and plasma was analysed by a validated HPLC‐UV method. No behavioural changes or alterations in health parameters were observed in the i.v. or i.m. groups of animals during or after (up to 7 days) drug administration. Plasma concentrations of MAA after i.v. and i.m. administrations of MT were detectable from 5 min to 10 h in all the horses. Plasma concentrations of AA were detectable in the same range of time, but in smaller amounts. Maximum concentration (Cmax), time to maximum concentration (Tmax) and AUMC0‐last of MAA were statistically different between the i.v. and i.m. groups. The AUCIM/AUCIV ratio of MAA was 1.06. In contrast, AUC0‐last of AA was statistically different between the groups (P < 0.05) with an AUCIM/AUCIV ratio of 0.54. This study suggested that the differences in the MAA and AA plasma concentrations found after i.m. and i.v. administrations of MT might have minor consequences on the pharmacodynamics of the drug.
Pharmacokinetics and distribution in interstitial and pulmonary epithelial lining fluid of danofloxacin in ruminant and preruminant calves
Authors: Mzyk D. A. , Baynes R. E. , Messenger K. M. , Martinez M. , Smith G. W.
Published: August 2016

The objective of this study was to compare active drug concentrations in the plasma vs. different effector compartments including interstitial fluid (ISF) and pulmonary epithelial lining fluid (PELF) of healthy preruminating (3‐week‐old) and ruminating (6‐month‐old) calves. Eight calves in each age group were given a single subcutaneous (s.c.) dose (8 mg/kg) of danofloxacin. Plasma, ISF, and bronchoalveolar lavage (BAL) fluid were collected over 96 h and analyzed by high‐pressure liquid chromatography. PELF concentrations were calculated by a urea dilution assay of the BAL fluids. Plasma protein binding was measured using a microcentrifugation system. For most preruminant and ruminant calves, the concentration–time profile of the central compartment was best described by a two‐compartment open body model. For some calves, a third compartment was also observed. The time to maximum concentration in the plasma was longer in preruminating calves (3.1 h) vs. ruminating calves (1.4 h). Clearance (CL/F) was 385.15 and 535.11 mL/h/kg in preruminant and ruminant calves, respectively. Ruminant calves maintained higher ISF/plasma concentration ratios throughout the study period compared to that observed in preruminant calves. Potential reasons for age‐related differences in plasma concentration–time profiles and partitioning of the drug to lungs and ISF as a function of age are explored.
Evaluation of the ability of Acinetobacter baumannii to form biofilms on six different biomedical relevant surfaces
Authors: Greene C. , Wu J. , Rickard A.H. , Xi C.
Published: August 2016

The human opportunistic pathogen, Acinetobacter baumannii, has the propensity to form biofilms and frequently cause medical device-related infections in hospitals. However, the physio-chemical properties of medical surfaces, in addition to bacterial surface properties, will affect colonization and biofilm development. The objective of this study was to compare the ability of A. baumannii to form biofilms on six different materials common to the hospital environment: glass, porcelain, stainless steel, rubber, polycarbonate plastic and polypropylene plastic. Biofilms were developed on material coupons in a CDC biofilm reactor. Biofilms were visualized and quantified using fluorescent staining and imaged using confocal laser scanning microscopy (CLSM) and by direct viable cell counts. Image analysis of CLSM stacks indicated that the mean biomass values for biofilms grown on glass, rubber, porcelain, polypropylene, stainless steel and polycarbonate were 0·04, 0·26, 0·62, 1·00, 2·08 and 2·70 μm3/μm2 respectively. Polycarbonate developed statistically more biofilm mass than glass, rubber, porcelain and polypropylene. Viable cell counts data were in agreement with the CLSM-derived data. In conclusion, polycarbonate was the most accommodating surface for A. baumannii ATCC 17978 to form biofilms while glass was least favourable. Alternatives to polycarbonate for use in medical and dental devices may need to be considered.

Significance and Impact of the Study

In the hospital environment, Acinetobacter baumannii is one of the most persistent and difficult to control opportunistic pathogens. The persistence of A. baumannii is due, in part, to its ability to colonize surfaces and form biofilms. This study demonstrates that A. baumannii can form biofilms on a variety of different surfaces and develops substantial biofilms on polycarbonate – a thermoplastic material that is often used in the construction of medical devices. The findings highlight the need to further study the in vitro compatibility of medical materials that could be colonized by A. baumannii and allow it to persist in hospital settings.
Spatiotemporal relationship between adult census size and genetic population size across a wide population size gradient
Authors: Bernos Thaїs A. , Fraser Dylan J.
Published: August 2016

Adult census population size (N) and effective number of breeders (Nb) are highly relevant for designing effective conservation strategies. Both parameters are often challenging to quantify, however, making it of interest to determine whether one parameter can be generalized from the other. Yet, the spatiotemporal relationship between N and Nb has not been well characterized empirically in many taxa. We analysed this relationship for 5–7 consecutive years in twelve brook trout populations varying greatly in N (49‐10032) and Nb (3‐567) and identified major environmental variables affecting the two parameters. N or habitat size alone explained 47–57% of the variance in Nb, and Nb was strongly correlated with effective population size. The ratio Nb/N ranged from 0.01 to 0.45 and increased at small N or following an annual decrease in N, suggesting density‐dependent constraints on Nb. We found no evidence for a consistent, directional difference between variability in Nb and/or Nb/N among small and large populations; however, small populations had more varying temporal variability in Nb/N ratios than large populations. Finally, Nb and Nb/N were 2.5‐ and 2.3‐fold more variable among populations than temporally within populations. Our results demonstrate a clear linkage between demographic and evolutionary parameters, suggesting that Nb could be used to approximate N (or vice versa) in natural populations. Nevertheless, using one variable to infer the other to monitor trends within populations is less recommended, perhaps even less so in small populations given their less predictable Nb vs. N dynamics.
Lanthanum carbonate: safety data after 10 years
Authors: Hutchison Alastair J , Wilson Rosamund J , Garafola Svetlana , Copley John Brian
Published: August 2016

Despite 10 years of post‐marketing safety monitoring of the phosphate binder lanthanum carbonate, concerns about aluminium‐like accumulation and toxicity persist. Here, we present a concise overview of the safety profile of lanthanum carbonate and interim results from a 5‐year observational database study (SPD405‐404; ClinicalTrials.gov identifier: NCT00567723). The pharmacokinetic paradigms of lanthanum and aluminium are different in that lanthanum is minimally absorbed and eliminated via the hepatobiliary pathway, whereas aluminium shows appreciable absorption and is eliminated by the kidneys. Randomised prospective studies of paired bone biopsies revealed no evidence of accumulation or toxicity in patients treated with lanthanum carbonate. Patients treated with lanthanum carbonate for up to 6 years showed no clinically relevant changes in liver enzyme or bilirubin levels. Lanthanum does not cross the intact blood–brain barrier. The most common adverse effects are mild/moderate nausea, diarrhoea and flatulence. An interim Kaplan–Meier analysis of SPD405‐404 data from the United States Renal Data System revealed that the median 5‐year survival was 51.6 months (95% CI: 49.1, 54.2) in patients who received lanthanum carbonate (test group), 48.9 months (95% CI: 47.3, 50.5) in patients treated with other phosphate binders (concomitant therapy control group) and 40.3 months (95% CI: 38.9, 41.5) in patients before the availability of lanthanum carbonate (historical control group). Bone fracture rates were 5.9%, 6.7% and 6.4%, respectively. After more than 850 000 person‐years of worldwide patient exposure, there is no evidence that lanthanum carbonate is associated with adverse safety outcomes in patients with end‐stage renal disease.
Transcriptome response ofLolium arundinaceumto its fungal endophyteEpichloë coenophiala
Authors: Dinkins Randy D. , Nagabhyru Padmaja , Graham Michelle A. , Boykin Deborah , Schardl Christopher L.
Published: August 2016

Tall fescue (Lolium arundinaceum) is one of the primary forage and turf grasses in temperate regions of the world. A number of favourable characteristics of tall fescue are enhanced by its seed‐transmissible fungal symbiont (endophyte)Epichloë coenophiala.

Our approach was to assemble the tall fescue transcriptome, then identify differentially expressed genes (DEGs) for endophyte‐symbiotic (E+) vs endophyte‐free (E−) clones in leaf blades, pseudostems, crowns and roots.RNA‐seq reads were used to construct a tall fescue reference transcriptome and compare gene expression profiles.

Over all tissues examined, 478DEGs were identified between the E+ and E− clones for at least one tissue (more than two‐fold;P < 0.0001, 238 E+ > E− and 240 E− > E+), although no genes were differentially expressed in all four tissues. Gene ontology (GO) terms,GO:0010200 (response to chitin),GO:0002679 (respiratory burst during defence response) andGO:0035556 (intracellular signal transduction) were significantly overrepresented among 25 E− > E+DEGs in leaf blade, and a number of otherDEGs were associated with defence and abiotic response.

In particular, endophyte effects on variousWRKYtranscription factors may have implications for symbiotic stability, endophyte distribution in the plant, or defence against pathogens.
The efficacy of intra‐alveolar 0.2% chlorhexidine gel on alveolar osteitis: a meta‐analysis
Authors: Zhou J , Hu B , Liu Y , Yang Z , Song J
Published: August 2016

Objectives

The objective of this meta‐analysis was to assess the effect of 0.2% chlorhexidine gel in preventing alveolar osteitis following mandibular third molar extraction(s).

Methods

PubMed, Cochrane Library, Embase, Web of Science, Science Direct and the references of identified articles were searched for relevant studies that met our eligibility criteria. Treatment effects were combined by meta‐analysis using RevMan 5.3 and Stata 12.0 software.

Results

We included 11 trials in this meta‐analysis. Compared to the control, 0.2% chlorhexidine gel reduced the risk of alveolar osteitis by 62% (RR = 0.38, 95% CI = 0.28–0.53, P < 0.00001) following mandibular third molar extraction(s). The subgroup analysis results indicated that 0.2% chlorhexidine gel reduced the risk of alveolar osteitis after mandibular third molar extraction(s) by 75% (RR = 0.25, 95% CI = 0.11–0.58) and 56% (RR = 0.44, 95% CI = 0.30–0.63) compared to no treatment and placebo, respectively. However, the occurrence of alveolar osteitis following mandibular third molar extraction(s) was not significantly different between 0.2% chlorhexidine gel and 0.12% chlorhexidine mouthwash (RR = 0.24, 95% CI = 0.06–1.00).

Conclusion

The results showed that 0.2% chlorhexidine gel was effective in preventing alveolar osteitis after lower third molar extraction(s).
Obtaining consensus regarding international transplantation continues to be difficult for pediatric centers in the United States
Authors: Lorts Angela , Ryan Thomas D. , Matheny Antommaria Armand H. , Lake Michael , Bucuvalas John
Published: August 2016

Organ transplant is life‐saving and any given organ may be valuable to a multitude of potential recipients. An allocation system must be used to reconcile the difference between supply and demand, and this system must take into account the impact that accepting international patients may have on the local system. The principles for allocation must be clear, equitable, provide utility and must be monitored so as to maintain public trust. The impact of the system on metrics deemed to be critical must be measured. Finally, strategies must take into account the local culture, size of the region to be supported, the number and experience of transplant centers, and the resources of the healthcare delivery system. Our focus is on the United States, recognizing that strategies and challenges may vary across countries.
Characteristics of Telephone Crisis Hotline Callers with Suicidal Ideation in Japan
Authors: Ohtaki Yuh , Oi Yuichi , Doki Shotaro , Kaneko Hidetoshi , Usami Kazuya , Sasahara Shinichiro , Matsuzaki Ichiyo
Published: August 2016

Hotline callers do not always have suicidal ideation and previous studies have noted that the rate of such callers is limited. Crisis hotline counselors must be able to identify high‐risk callers in order to provide appropriate support. This study investigated the characteristics of Japanese crisis hotline callers in 2012 (N = 541,694) and is the first to analyze crisis hotline data for all parts of Japan over 1 year. About 14% of the callers had suicidal ideation and 6% had a history of attempted suicide. The odds ratio for suicidal ideation among those with a history of attempted suicide was 15.5. The suicidal ideation rate was much smaller compared to previous studies in other countries. There is a psychological barrier that must be broken for high‐risk people to use support hotlines. In addition, attempted suicide is a strong exclusive predisposing factor for death due to suicide; therefore, counselors should pay careful attention to callers with a history of attempted suicide. The characteristics of Japanese crisis hotline callers and the features of suicidal ideation revealed in the present study are expected to be useful in developing telephone crisis hotline strategies.