bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression and prognostic value of microRNA‐26a and microRNA‐148a in gastric cancer
Authors: Qiu Xiaonan , Zhu Haixia , Liu Sang , Tao Guoquan , Jin Jing , Chu Haiyan , Wang Meilin , Tong Na , Gong Weida , Zhao Qinghong , Qiang Fulin , Zhang Zhengdong
Published: August 2016

Background and Aim

In our previous study, we demonstrated that four microRNAs (miRNAs) (miR‐26a, miR‐142‐3p, miR‐148a, and miR‐195) that were downregulated in both plasma and tumor tissues were confirmed to be promising non‐invasive diagnostic biomarkers for gastric cancer (GC).

Methods

We used the quantitative reverse transcription polymerase chain reaction to assess the expression levels of the four miRNAs from paraffin‐embedded surgical specimens of GC patients. Kaplan–Meier curves and log‐rank test were applied to predict the correlation between miRNAs and cumulative overall survival (OS) of patients with GC. Besides, we performed in vitro assays including cell proliferation, migration, invasion and colony formation, and apoptosis.

Results

The median of miRNA expression in paraffin‐embedded tissues were used as the cutoff value to classify patients into high or low expression groups. Down‐regulation of miR‐26a and miR‐148a was significantly associated with shorter OS of GC patients either in the test set (miR‐26a: P = 0.009; miR‐148a: P = 0.005) or the validation set (miR‐26a: P = 0.011; miR‐148a: P = 0.024). When two sets were combined, Cox regression analysis demonstrated that both of miR‐26a and miR‐148a were independent prognostic factors for predicting OS of patients with GC (miR‐26a: HR = 0.76, 95% CI = 0.61–0.94; miR‐148a: HR = 0.73, 95% CI = 0.58–0.91). Furthermore, elevated expression of miR‐26 significantly suppressed cell proliferation, migration, invasion and colony formation, and induced apoptosis of MGC‐803 cells compared with negative control groups (P < 0.05).

Conclusion

These findings supported miR‐26a and miR‐148a could serve as potential prognostic biomarkers for GC.
Evidence for the association between IgG‐antimitochondrial antibody and biochemical response to ursodeoxycholic acid treatment in primary biliary cholangitis
Authors: Tang Libo , Zhong Ruihua , He Xuanqiu , Wang Weibin , Liu Jinhong , Zhu Youfu , Li Yongyin , Hou Jinlin
Published: August 2016

Background and Aim

Antimitochondrial antibody (AMA) is considered the serological hallmark of primary biliary cholangitis (PBC), while data regarding the profile of AMA during ursodeoxycholic acid (UDCA) treatment are scarce. Here, we assessed the influence of UDCA treatment on titers of AMA and factors relevant to its production.

Methods

Serum IgA‐AMA, IgM‐AMA, IgG‐AMA, B cell‐activating factor of the tumor necrosis factor family (BAFF), and the frequency of circulating plasmablasts were detected in PBC patients, including those who received UDCA therapy for 24 weeks, healthy controls, chronic hepatitis B patients, and autoimmune hepatitis patients. Consecutive liver sections from controls and PBC patients were stained by immunohistochemistry for detection of intrahepatic CD38+, IgA+, IgM+, and IgG+ cells.

Results

Significant decrease in titers of IgG‐AMA was found only confined to PBC patients with biochemical response to UDCA treatment (P = 0.005), and similar pattern was also observed at week 24 in quantifying circulating plasmablasts (P = 0.025) and serum BAFF (P = 0.013). Notably, positive correlation between serum BAFF levels and titers of IgG‐AMA, and the frequency of circulating plasmablasts were observed in PBC patients (r = 0.464, P = 0.034 and r = 0.700, P < 0.001, respectively). Additionally, in situ staining revealed significant accumulation of CD38+ and IgG+ cells within the portal tracts of PBC liver.

Conclusions

Decreased titers of serum IgG‐AMA are associated with biochemical response to UDCA treatment, implicating the potentiality of this hallmark in therapeutic response evaluation and the beneficial effect of UDCA on humoral immunity in PBC patients.
Recycle, Bury, or Burn Wood Waste Biomass?: LCA Answer Depends on Carbon Accounting, Emissions Controls, Displaced Fuels, and Impact Costs
Authors: Morris Jeffrey
Published: August 2016

This study extends existing life cycle assessment (LCA) literature by assessing seven environmental burdens and an overall monetized environmental score for eight recycle, bury, or burn options to manage clean wood wastes generated at construction and demolition activity sites. The study assesses direct environmental impacts along with substitution effects from displacing fossil fuels and managed forest wood sourcing activities. Follow‐on effects on forest carbon stocks, land use, and fuel markets are not assessed. Sensitivity analysis addresses landfill carbon storage and biodegradation rates, atmospheric emissions controls, displaced fuel types, and two alternative carbon accounting methods commonly used for waste management LCAs. Base‐case carbon accounting considers emissions and uptakes of all biogenic and fossil carbon compounds, including biogenic carbon dioxide. Base‐case results show that recycling options (recycling into reconstituted wood products or into wood pulp for papermaking) rank better than all burning or burying options for overall monetized score as well as for climate impacts, except that wood substitution for coal in industrial boilers is slightly better than recycling for the climate. Wood substitution for natural gas boiler fuel has the highest environmental impacts. Sensitivity analysis shows the overall monetized score rankings for recycling options to be robust except for the carbon accounting method, for which all options are highly sensitive. Under one of the alternative methods, wood substitution for coal boiler fuel and landfill options with high methane capture efficiency are the best for the overall score; recycling options are next to the worst. Under the other accounting alternative, wood substitution for coal and waste‐to‐energy are the best, followed by recycling options.
Intracerebroventricular Oxytocin Self‐Administration in Female Rats
Authors: Donhoffner M. E. , Goings S. P. , Atabaki K. , Wood R. I.
Published: August 2016

Oxytocin (OT) is a neuromodulator that facilitates pair‐bonding, maternal care and social approach. OT is considered to promote these social behaviours by enhancing the salience and reinforcing effects of relevant social stimuli. There is the additional possibility that OT per se may be rewarding. To test this, we investigated whether female rats would voluntarily self‐administer OT. Female Long–Evans rats were ovariectomised and then received an oestrogen implant and an i.c.v. cannula. Rats were tested in an operant chamber with active and inactive levers. They were initially tested for 4 h/day on a fixed‐ratio 5 schedule for self‐administration of artificial cerebral spinal fluid (aCSF) for 5 days, followed by aCSF, or OT, at 1 or 10 ng/μl for another 5 days. Rats self‐administering aCSF made 36.2 ± 6.2 active lever responses/4 h versus 14.9 ± 3.4 inactive responses. Responses for 1 ng/μl OT were similar. However, rats self‐administering 10 ng/μl OT made significantly more active lever responses (67.8 ± 12.0 per 4 h), and received 121.4 ± 21.0 ng OT/4 h. To determine whether reduced anxiety contributes to the reinforcing effects of OT, rats received an infusion of aCSF or OT at 0.3 or 3.0 μg immediately before testing on the elevated plus maze. There was no effect of OT on anxiety as reflected by percentage time spent on the open arms, as well as no effect of OT on locomotion as measured either by the number of closed arm entries or the number of total arm entries. These results suggest that OT may be rewarding, and that this is not a result of the anxiolytic effects of OT.
Exploring psychological safety as a component of facilitation within the Promoting Action on Research Implementation in Health Services framework
Authors: Brown Donna , McCormack Brendan
Published: August 2016

Aims and objectives

To explore holistic facilitation as an approach to enable the healthcare team to critically analyse practice and enhance patient care.

Background

Globally, the challenge of changing healthcare practices for enhanced patient care is the focus of much attention. Facilitation is emerging as an important approach to assist healthcare teams to explore and improve their practice. Within the Promoting Action on Research Implementation in Health Services framework, which has been tested in an international arena, facilitation is a key element of operationalising collaborative changes in practice. This study uses the framework to explore holistic facilitation and the concept of psychological safety.

Design

An Emancipatory Action Research approach was used.

Methods

Facilitated critical reflection was undertaken with the healthcare team working in an abdominal surgical unit. In addition, the lead researcher maintained a reflexive journal. Data were analysed using thematic analysis. Eighty‐five per cent (n = 48) of nursing staff and individual participants from other parts of the healthcare team (n = 3) participated in the two‐year study.

Results

Data revealed 14 sub‐themes that impacted upon the culture of the unit. These were as follows: support, leadership, oppressed behaviours, communication, interruptions, power imbalance, horizontal violence, threat, autonomy, distorted perceptions, vulnerability, value, trust and time. Psychological safety, leadership and oppressed behaviours emerged as three key themes in the practice context.

Conclusions

There is a need to create psychologically safe spaces in environments where insufficient support, weak leadership and oppressed behaviours are apparent. Psychological safety enables individuals to feel safe to engage in difficult conversations and consider changes to practice. In a theoretical contribution to the area of facilitation, it is proposed that the additional element of psychological safety needs to be incorporated into facilitation models, in particular, the Promoting Action on Research Implementation in Health Services framework, to more accurately reflect the complexities of working with healthcare teams.

Relevance to practice

The pressure on healthcare environments continues to increase. To achieve the necessary skills to lead and develop services requires more than simply highlighting what is wrong with practice. Creating psychologically safe spaces, using holistic facilitation, is essential to enabling healthcare teams to critically analyse practice and enhance patient care.
Prognosis of endometrial cancer patients with and without symptoms at recurrence
Authors: Yoshiba Takahiro , Takei Yuji , Machida Shizuo , Taneichi Akiyo , Sato Naoto , Takahashi Suzuyo , Takahashi Yoshifumi , Saga Yasushi , Matsubara Shigeki , Fujiwara Hiroyuki
Published: August 2016

Aim

During routine follow‐up for postoperative endometrial cancer, we have encountered patients with and without symptoms at recurrence. In this study, we investigated whether or not there is a difference in the prognosis between patients with and without symptoms at recurrence.

Methods

We reviewed endometrial cancer patients who had been treated in our hospital between 1998 and 2007. Routine follow‐up was conducted by our facility criteria. We investigated recurrence‐free survival (RFS), presence or absence of symptoms at recurrence, overall survival from recurrence (OSFR), and overall survival (OS).

Results

The subjects were 293 patients. Recurrence was detected in 46 patients. The median RFS was 15 (1–103) months. At the time of recurrence, symptoms were present in 14 patients and absent in 32 patients. In groups with and without symptoms at recurrence, the median OSFR were 36 (2–100) and 45 (2–139) months, respectively. The median OS were 55 (6–163) and 100 (11–178) months, respectively. There were no significant differences in either parameter. Independent prognostic factors for OSFR and OS were histopathologic types other than endometrioid carcinoma (vs endometrioid carcinoma, hazard ratio = 3.102 and 3.008, respectively) and RFS of 14 months or shorter (vs 15 months or longer, hazard ratio = 2.378 and 3.739, respectively).

Conclusion

There was no difference in the prognosis between the groups with and without symptoms at recurrence. Independent prognostic factors of recurrent patients were histopathologic types and RFS. A large‐scale study should be conducted to examine the necessity of routine follow‐up for detecting recurrence in the absence of symptoms.
Virological and cytological clearance in laser vaporization and conization for cervical intra‐epithelial neoplasia grade 3
Authors: Mariya Tasuku , Nishikawa Akira , Sogawa Kanae , Suzuki Riri , Saito Masae , Kawamata Akari , Shimizu Ayumi , Nihei Takehito , Sonoda Tomoko , Saito Tsuyoshi
Published: August 2016

Aim

Cervical intra‐epithelial neoplasia (CIN) is the precancerous stage of cervical cancer. Standard treatment for high‐grade CIN is conization of the cervix. The risk of preterm birth following conization has been discussed recently. In contrast, laser vaporization is believed not to affect perinatal outcome, but the long‐term effectiveness of each surgical procedure is still unclear. The aim of this prospective unmatched‐cohort study was therefore to compare virological and cytological clearance and recurrence risk between conization and vaporization for CIN3.

Methods

Subject consisted of CIN3 patients treated at the present hospital between 2007 to 2011 and followed up until December 2014. One hundred and one patients were treated with laser conization, and 137 with vaporization. The surgical procedure was selected on the basis of colposcopy, pathological grade and patient's hope for pregnancy.

Results

There were no significant differences in cure rate, human papilloma virus (HPV) clearance rate or recurrence rates between the conization and vaporization groups. Risk ratio of recurrence for each surgical procedure adjusted for age and HPV persistence status were analyzed on Cox proportional hazards modeling. Recurrence risk ratio for patients treated by vaporization was 6.21 (95%CI: 0.65–59.19; P = 0.111) compared with conization and there were no significant differences. No adverse pregnancy outcome was observed in the vaporization group compared with conization.

Conclusions

Laser vaporization is useful for young patients with CIN3 who hope for pregnancy in the future.
Moral Motivation as a Dynamic Developmental Process: Toward an Integrative Synthesis
Authors: Kaplan Ulas
Published: August 2016

The real‐life complexity of moral motivation can be examined and explained by reintegrating time and development into moral inquiry. This article is one of the possible integrative steps in this direction. A dynamic developmental conception of moral motivation can be a useful bridge toward such integration. A comprehensive view of moral motivation is presented. Moral motivation is reconceptualized as a developmental process of self‐organization and self‐regulation out of which moral judgment and action emerge through the interplay of dynamically intertwined cognitive and emotional components. Moral identity is proposed to emerge from long‐term self‐organization of moral motivation. In turn, as a higher‐order construct, moral identity has a top‐down influence on real‐time self‐organization. The article includes an account of short‐term changes in moral motivation, and an account that connects real‐time moral functioning with long‐term changes. Moral motivation is qualified as a dynamic developmental process on the basis of self‐organization, multicausality, nonlinearity, interconnectedness of time scales and substantial intrapersonal variability through motivational pluralism.
Evaluation of Weight Loss Over Time in Cats with Chronic Kidney Disease
Authors: Freeman L.M. , Lachaud M.‐P. , Matthews S. , Rhodes L. , Zollers B.
Published: August 2016

Background

Thin body condition and weight loss are common in cats with chronic kidney disease (CKD). However, the time course and progression of weight loss before and after diagnosis have not been thoroughly evaluated.

Hypothesis/Objectives

To describe weight loss in cats withCKDbefore and after diagnosis and its relationship to survival.

Animals

A total of 569 cats (55.5% females and 44.5% males) withCKDfrom 6USveterinary practices for which International Renal Interest Society (IRIS) stage, age, date ofCKDdiagnosis, and at least two body weight measurements were available.

Methods

Body weight measurements were analyzed by time windows and polynomial growth curve analysis. Survival analysis was performed by Kaplan–Meier curves and log‐rank tests.

Results

Median age at diagnosis was 14.9 years (range, 5.0–22.8 years). Cats were categorized at diagnosis asIRISstage 1 (n = 34 [6%]), stage 2 (n = 345 [61%]), stage 3 (n = 141 [25%]), and stage 4 (n = 49 [9%]). Median body weight at diagnosis was 4.2 kg (range, 1.6–9.9 kg). Cats lost a median of 8.9% of body weight in the 12 months before diagnosis, but weight loss was already present 3 years before diagnosis and accelerated after diagnosis ofCKD. Cats <4.2 kg at the time of diagnosis had significantly shorter survival time compared to cats ≥ 4.2 kg at diagnosis (P< .0001).

Conclusions and Clinical Importance

Weight loss can be detected in cats before diagnosis ofCKD, accelerates after diagnosis, and is associated with shorter survival. Tracking body weight may help clinicians in earlier diagnosis ofCKD.
The Effect of Moderate Dietary Protein and Phosphate Restriction on Calcium‐Phosphate Homeostasis in Healthy Older Cats
Authors: Geddes R.F. , Biourge V. , Chang Y. , Syme H.M. , Elliott J.
Published: August 2016

Background

Dietary phosphate and protein restriction decreases plasma PTH and FGF‐23 concentrations and improves survival time in azotemic cats, but has not been examined in cats that are not azotemic.

Hypothesis

Feeding a moderately protein‐ and phosphate‐restricted diet decreases PTH and FGF‐23 in healthy older cats and thereby slows progression to azotemic CKD.

Animals

A total of 54 healthy, client‐owned cats (≥ 9 years).

Methods

Prospective double‐blinded randomized placebo‐controlled trial. Cats were assigned to test diet (protein 76 g/Mcal and phosphate 1.6 g/Mcal) or control diet (protein 86 g/Mcal and phosphate 2.6 g/Mcal) and monitored for 18 months. Changes in variables over time and effect of diet were assessed by linear mixed models.

Results

A total of 26 cats ate test diet and 28 cats ate control diet. There was a significant effect of diet on urinary fractional excretion of phosphate (P = 0.045), plasma PTH (P = 0.005), and ionized calcium concentrations (P = 0.018), but not plasma phosphate, FGF‐23, or creatinine concentrations. Plasma PTH concentrations did not significantly change in cats fed the test diet (P = 0.62) but increased over time in cats fed the control diet (P = 0.001). There was no significant treatment effect of the test diet on development of azotemic CKD (3 of 26 (12%) test versus 3 of 28 (11%) control, odds ratio 1.09 (95% CI 0.13–8.94), P = 0.92).

Conclusions and Clinical Importance

Feeding a moderately protein‐ and phosphate‐restricted diet has effects on calcium‐phosphate homeostasis in healthy older cats and is well tolerated. This might have an impact on renal function and could be useful in early chronic kidney disease.
Individual identification of wild giant pandas from camera trap photos – a systematic and hierarchical approach
Authors: Zheng X. , Owen M. A. , Nie Y. , Hu Y. , Swaisgood R. R. , Yan L. , Wei F.
Published: August 2016

The scientific and conservation‐management value of using camera traps is greatly enhanced if the identity of individual animals ‘captured’ can be assigned. Identification of individuals is necessary to make unbiased estimates of population parameters, and can allow for the generation of more robust inferences from studies of spatial and behavioral ecology. Here we tested the utility of an approach to individually identify wild giant pandas Ailuropoda melanoleuca from camera trap images, by cataloguing and careful scrutiny of numerous traits. We developed our identification strategy first by analyzing images of known (captive) individuals (N = 7). We then deployed camera traps at 23 control sites and at seven camera trap arrays ‘baited’ with conspecific decoys, in Foping Nature Reserve, China. From a sample of 12 871 photographs, and using the method we developed with known individuals, we were able to identify 11 individual giant pandas. We tested the repeatability of this approach using a double blind test with 12 naïve volunteers, achieving a relatively high inter‐observer agreement of 80%, which was increased to 93% when observers reported a high degree of confidence. We also found that image quality was significantly higher at decoy sites than at control sites. We suggest that this approach will be useful for future field projects, allowing researchers to address a broader array of questions and provide new insights into panda ecology and conservation.
Human milk expression as a sole or ancillary strategy for infant feeding: a qualitative study
Authors: O'Sullivan Elizabeth J. , Geraghty Sheela R. , Rasmussen Kathleen M.
Published: August 2016

In the United States, a significant proportion of human milk (HM) is now fed to infants from bottles. This mode of infant feeding is rarely measured or described in research studies or monitored by national surveillance systems. Consequently, little is known about expressed‐HM feeding as an infant feeding strategy. Our objective was to understand how mothers use HM expression and expressed‐HM feeding as a sole strategy or in combination with at‐the‐breast feeding to feed HM to their infants. We conducted semi‐structured interviews with 41 mothers with experience of HM expression and infants under three years of age. Data were analysed using a grounded theory approach for sub‐themes related to the pre‐selected major themes of maternal HM production and infant HM consumption. Within the major theme of maternal HM production, sub‐themes related to maternal over‐production of HM. Many mothers produced more HM than their infant was consuming and stored it in the freezer. This enabled some infants to consume HM weeks or months after it was expressed. Within the major theme of infant HM consumption, the most salient sub‐theme related to HM‐feeding strategies. Four basic HM‐feeding strategies emerged, ranging from predominant at‐the‐breast feeding to exclusive expressed‐HM feeding. The HM‐feeding strategies and trajectories highlighted by this study are complex, and most mothers fed HM both at‐the‐breast and from a bottle—information that is not collected by the current national breastfeeding survey questions. To understand health outcomes associated with expressed‐HM feeding, new terminology may be needed.
Fluorescent reporter analysis revealed the timing and localization of AVR‐Pia expression, an avirulence effector of Magnaporthe oryzae
Authors: Sornkom Worawan , Miki Shinsuke , Takeuchi Saori , Abe Ayumi , Asano Kozo , Sone Teruo
Published: August 2016

In order to facilitate infection, the rice blast pathogen Magnaporthe oryzae secretes an abundance of proteins, including avirulence effectors, to diminish its host's defences. Avirulence effectors are recognized by host resistance proteins and trigger the host's hypersensitive response, which is a rapid and effective form of innate plant immunity. An understanding of the underlying molecular mechanisms of such interactions is crucial for the development of strategies to control disease. However, the expression and secretion of certain effector proteins, such as AVR‐Pia, have yet to be reported. Reverse transcription‐polymerase chain reaction (RT‐PCR) revealed that AVR‐Pia was only expressed during infection. Fluorescently labelled AVR‐Pia indicated that AVR‐Pia expression was induced during appressorial differentiation in the cells of both rice and onion, as well as in a penetration‐deficient (Δpls1) mutant capable of developing melanized appressoria, but unable to penetrate host cells, suggesting that AVR‐Pia expression is independent of fungal penetration. Using live‐cell imaging, we also documented the co‐localization of green fluorescent protein (GFP)‐labelled AVR‐Pia and monomeric red fluorescent protein (mRFP)‐labelled PWL2, which indicates that AVR‐Pia accumulates in biotrophic interfacial complexes before being delivered to the plant cytosol. Together, these results suggest that AVR‐Pia is a cytoplasmic effector that is expressed at the onset of appressorial differentiation and is translocated to the biotrophic interfacial complex, and then into the host's cytoplasm.
Mating senescence and male reproductive organ size in the Mexican fruit fly
Authors: Reyes‐Hernández Martha , Pérez‐Staples Diana
Published: August 2016

Ageing can reduce the probability that individuals reproduce. The present study investigates whether ageing influences the mating frequency of mass‐reared fertile and sterile Mexican fruit flies Anastrepha ludens (Loew). The ability of males of different ages to inhibit female remating is also determined, and the growth of male reproductive organs is measured as they age. Young males (6 days old) have a lower mating frequency than older males, and also have a lower capacity to inhibit female remating than older males. However, 7‐day‐old males are as likely to inhibit female remating as older males. Young males also have smaller reproductive organs than middle‐aged (21‐day‐old) or senescent males (57‐day‐old). These results have implications for the sterile insect technique because sterilized males of A. ludens are released in the field 6 days after emergence. The highest mating frequency, the lowest mating latency and the largest size of testes are observed at 21 days of age. Older males (57 days old) have more sperm in their seminal vesicles than young males (6 and 9 days old). Accessory glands take longer to grow to their complete size compared with testes, and mating frequency is more closely associated with accessory gland size than testes size. Furthermore, there are more sperm in the seminal vesicles during the afternoon period of peak sexual activity than during the morning when sexual activity is absent. These results indicate that, even at the onset of reproductive senescence, mass‐reared males of A. ludens are still capable of mating, as well as inhibiting remating in females.
Potato cultivar Etola exhibits hypersensitive resistance to PVYNTN and partial resistance to PVYZ‐NTN and PVYN‐Wi strains and strain‐specific alterations of certain host miRNAs might correlate with symptom severity
Authors: Yin Z. , Xie F. , Michalak K. , Pawełkowicz M. , Zhang B. , Murawska Z. , Lebecka R. , Zimnoch‐Guzowska E.
Published: August 2016

This study demonstrates the new sources of resistance available in potato cv. Etola, which represent multiple strain‐specific resistance genes against three strains of Potato virus Y (PVY). Etola is the first documented cultivar of this sort in Europe that exhibits hypersensitive resistance (HR) to PVYNTN isolate PVY‐3202, and different levels of partial resistance to PVYN‐Wi isolate PVY‐3411 and PVYZ‐NTN isolate PVY‐3303. The isolate PVY‐3411 induced severe symptoms and faster systemic viral coat protein and RNA accumulation in the noninoculated upper leaves, whereas PVY‐3303 caused mild symptoms and delayed viral spreading. This study provides the first example of strain‐specific alteration of a set of host microRNAs (miRNAs) and their targets in the potato–PVY interaction. The tested miRNAs and targets are altered only in plants of cv. Etola infected with PVY‐3411 but not those infected with PVY‐3303 nor PVY‐3202. The up‐regulation of stu‐miR162, stu‐miR168a and miR172e, together with their target transcripts, DCL1, AGO1‐2 and TOE3, respectively, in PVY‐3411‐infected plants correlates with high abundance of HC‐Pro RNA encoding an RNA‐silencing suppressor and might be linked with the severe symptoms in leaves. Moreover, PVY‐3411 causes parallel increases in two members of stu‐miR482 and their mRNA targets Gpa2 and CC‐NBS‐LRR that are involved in the defence response.
Motor‐evoked potentials reveal a motor‐cortical readout of evidence accumulation for sensorimotor decisions
Authors: Hadar Aviad A. , Rowe Paula , Di Costa Steven , Jones Alexander , Yarrow Kielan
Published: August 2016

Many everyday activities require time‐pressured sensorimotor decision making. Traditionally, perception, decision, and action processes were considered to occur in series, but this idea has been successfully challenged, particularly by neurophysiological work in animals. However, the generality of parallel processing requires further elucidation. Here, we investigate whether the accumulation of a decision can be observed intrahemispherically within human motor cortex. Participants categorized faces as male or female, with task difficulty manipulated using morphed stimuli. Transcranial magnetic stimulation, applied during the reaction‐time interval, produced motor‐evoked potentials (MEPs) in two hand muscles that were the major contributors when generating the required pinch/grip movements. Smoothing MEPs using a Gaussian kernel allowed us to recover a continuous time‐varying MEP average, comparable to an EEG component, permitting precise localization of the time at which the motor plan for the responding muscle became dominant. We demonstrate decision‐related activity in the motor cortex during this perceptual discrimination task, suggesting ongoing evidence accumulation within the motor system even for two independent actions represented within one hemisphere.
Binary Auto-Regressive Geometric Modelling in a DNA Context
Authors: Gouveia Sónia , Scotto Manuel G. , Weiß Christian H. , Ferreira Paulo Jorge S. G.
Published: August 2016

Symbolic or categorical sequences occur in many contexts and can be characterized, for example, by integer-valued intersymbol distances or binary-valued indicator sequences. The analysis of these numerical sequences often sheds light on the properties of the original symbolic sequences. This work introduces new statistical tools for exploring auto-correlation structure in the indicator sequences, for the specific case of deoxyribonucleic acid (DNA) sequences. It is known that the probability distribution of internucleotide distances of DNA sequences deviates significantly from the distribution obtained by assuming independent random placement (i.e. the geometric distribution) and that the deviations can be used either to discriminate between species or to build phylogenetic trees. To investigate the extent to which auto-correlation structure explains these deviations, the 0–1 indicator sequence of each nucleotide (A, C, G and T) is endowed with a binary auto-regressive (AR) model of optimum order. The corresponding binary AR geometric distribution is derived analytically and compared with the observed internucleotide distance distribution by appropriate goodness-of-fit testing. Results in 34 mitochondrial DNA sequences show that the hypothesis of equal observed/expected frequencies is seldom rejected when a binary AR model is considered instead of independence (76/136 versus 125/136 rejections at the 1% level), in spite of χ2-testing tending to reject for large samples, regardless of how close observed/expected values are. Furthermore, binary AR structure also leads to a median discrepancy reduction of 90% for G, 80% for C, 60% for T and 30% for nucleotide A. Therefore, these models are useful to describe the dependences within a given nucleotide and encourage the development of a model-based framework to compact internucleotide distance information and to understand DNA differences among species further.
Critical Components in Implementing Evidence‐based Practice: A Multiple Case Study of Individual Placement and Support for People with Psychiatric Disabilities
Authors: Bergmark Magnus , Bejerholm Ulrika , Markström Urban
Published: August 2016

When developing Community Mental Health Services to support people with psychiatric disabilities, European countries are advocating evidence‐based practice (EBP). Individual Placement and Support (IPS) is an evidence‐based model designed to support people in acquiring and maintaining competitive employment. Implementation science is a growing research field, with a focus on components that impact the process of implementing EBP programmes. In this multiple case study, we have followed three IPS demonstration sites for two years, in order to describe and analyze barriers and facilitators for implementation, according to constructs described in the Consolidated Framework for Implementation Research (Damschroder et al. 2009). The results highlight the importance of strategic networking, as well as the need for planning and preparations carried out before the start of an EBP programme, since deficiencies related to these constructs are difficult to compensate for.
An open source GIS‐based Planning Support System: Application to the land use plan of La Troncal, Ecuador
Authors: Santé Inés , Pacurucu Natalia , Boullón Marcos , García Andrés Manuel , Miranda David
Published: August 2016

Planning Support Systems (PSS) comprise a wide variety of geo‐technological tools related to GIS and spatial modeling aimed at addressing land planning processes. This article describes the OpenRules system, a PSS based on a previous system called RULES. Among OpenRules new features are its architecture, based exclusively on free and open source software, and its applicability to all land use types, including rural and urban uses. In addition, OpenRules incorporates an unlimited number of land evaluation factors and a new objective in land use spatial allocation. OpenRules has been programmed in Java and implemented as a module of the free GIS software gvSIG, with full integration between the GIS and the decision support tools. Decision support tools include multicriteria evaluation, multiobjective linear programming and heuristic techniques, which support three basic stages of land use planning processes, namely land suitability evaluation, land use area optimization and land use spatial allocation. The application of OpenRules to the region of La Troncal, Ecuador, demonstrates its capability to generate alternative and coherent solutions through a scientific and justified procedure at low cost in terms of time and resources.
The human platelet alloantigen profile in blood donors from Amazonas, Brazil
Authors: Portela C. N. , Schriefer A. , Albuquerque S. R. L. , Perdomo R. T. , Parente A. F. A. , Weber S. S.
Published: August 2016

Background

Human platelet antigens (HPAs) are alloantigens derived from polymorphisms in platelet‐surface glycoproteins. The occurrence of alloantibodies against HPAs can lead to platelet destruction and subsequent thrombocytopenia. Brazilians have a high rate of racial admixture, and the knowledge of HPA polymorphisms in particular donors from north Brazil, who have a large Amerindian influence, is a relevant strategy to prevent alloimmunisation.

Objective

Our aim was investigate the HPA allele's frequencies in the Amazonas blood donors.

Methods

We performed HPA genotyping among 200 Amazonas blood donors by microarray for 11 HPA biallelic systems, including six of the most clinically significant systems (HPA‐1 to ‐5 and ‐15) and five others (HPA‐6 to ‐9 and ‐11) that have been also associated with alloimmunisation, amounting to 22 HPA alleles.

Results

The obtained allele frequencies were compared with data of 38 populations worldwide to determine the hierarchical relationship and estimated the probability of mismatch platelets. The allele frequencies were 0·862 for HPA‐1a, 0·137 for HPA‐1b, 0·852 for HPA‐2a, 0·147 for HPA‐2b, 0·665 for HPA‐3a, 0·335 for HPA‐3b, 0·995 for HPA‐4a, 0·005 for HPA‐4b, 0·892 for HPA‐5a, 0·107 for HPA‐5b, 0·997 for HPA‐9a, 0·005 for HPA‐9b, 0·502 for HPA‐15a and 0·497 for HPA‐15b. The incompatibility risks are higher for HPA‐15 and HPA‐3, followed by HPA‐1, ‐2 and ‐5.

Conclusion

We found differences among populations worldwide, and it is interesting to note the indigenous and European influences in this region, reinforcing the heterogeneity in the ancestry of Brazilians. The results will be helpful in providing information for platelet transfusion to avoid alloimmunisation.
Platelet concentrate functionality assessed by thromboelastography or rotational thromboelastometry
Authors: Arbaeen Ahmad F. , Serrano Katherine , Levin Elena , Devine Dana V.
Published: August 2016

BACKGROUND

There is poor correlation between in vivo platelet concentrate (PC) transfusion outcome and in vitro tests, which typically do not test the functional effectiveness of platelets (PLTs), but rather measure PLT characteristics. We hypothesize that the application of thromboelastography (TEG) or rotational thromboelastometry (ROTEM) to evaluate the procoagulant activity of stored PLTs can predict PLT quality and, ultimately, distinguish among hyper‐ and nonresponsive PCs. Additionally, we hypothesize that due to their procoagulant properties, PLT microvesicles (PMVs) contribute to the clot signature in these methods.

STUDY DESIGN AND METHODS

After the TEG assays were validated, buffy coat PCs were evaluated during the storage time and reconstituted with frozen plasma to different PLT concentrations. Poor quality PCs were generated and assessed by TEG and other in vitro tests. The contribution of PMVs to the TEG clot signature was assessed.

RESULTS

Hemostatic analysis showed no significant change in maximum amplitude (MA) during storage of PCs up to Day 10. On Day 8 of storage, PCs that had been manipulated to have poor quality showed a significant decrease in MA. PMV‐rich samples contributed to a significant increase in MA, and PMV count showed a significant correlation with maximum clot formation (r = 0.51, p < 0.01).

CONCLUSION

TEG was optimized for use with buffy coat PCs, although it was found to lack sensitivity to detect normal storage‐related quality changes. Hemostatic measurement was sufficiently sensitive to dissect PLT and PMV contributions to clot formation and to detect PCs stored under poor conditions.
The effect of blowing pressure, lip force and tonguing on transients: A study using a clarinet-playing machine
Authors: Li Weicong , Almeida André , Smith John , Wolfe Joe
Published: August 2016

Wind instrument players control the initial and final transients of notes using breath, lips, and tonguing. This paper uses a clarinet-playing machine and high-speed camera to investigate how blowing pressure, lip force, and tonguing parameters affect transients. After tongue release, the reed quickly comes to rest, losing its mechanical energy. However, the changing aperture past the reed rapidly changes the airflow. For pressure above the oscillation threshold, successive interactions between reflections of this pulse of airflow and the reed produce an exponential increase in the sound. The rates r of exponential increase in the fundamental of the sound range from several tens to several hundreds of dB s−1, as functions of blowing pressure and lip force. Because the reed's initial mechanical energy is lost, tongue force and acceleration have little effect on r. However, larger tongue force and acceleration produce more rapid changes in flow, which start notes sooner after tongue release. Further, large tongue force increases the third harmonic during the transient. There is a hysteresis region on the (pressure, lip force) plane where regenerative oscillation is not produced spontaneously by increasing blowing pressure only. Here, tongue action can initiate sustained notes at low pressure.
Impact of Climatic Conditions on Physical Activity: A 2-Year Cohort Study in the Arabian Gulf Region
Authors: Al-Mohannadi Abdulla S. , Farooq Abdulaziz , Burnett Angus , Van Der Walt Mercia , Al-Kuwari Mohamed Ghaith
Published: August 2016

Background:

Little is known about the effects that climatic conditions, especially extreme heat, have on physical activity (PA) levels. The aim of this 2-year cohort analysis undertaken in the Arabian Gulf region was to assess changes in objectively-assessed PA as a result of changes in climatic conditions.

Methods:

A total of 2088 adults (1390 men and 698 women) from many regions of the world were enrolled in a community health program in Qatar, were included in this study. For 2 years participants recorded daily step count using an Omron HJ-720 ITC pedometer. Daily climate parameters included temperature, relative humidity and other conditions.

Results:

From linear mixed model analysis it was evident that higher average temperature and humidity, and the Wet bulb Globe Temperature (WbGT), resulted in a reduction of the number of steps taken per day. Analysis of interaction effects also revealed that the effects of heat stress were equivalent across gender, age, and the region participants came from according to a World Health Organization classification scheme.

Conclusions:

Increased temperature and humidity are associated with a reduction in the number of steps taken per day. Community-based PA programs in hot hot/humid climates should consider novel approaches to increase PA levels.
Coincident signals from GPCRs and receptor tyrosine kinases are uniquely transduced by PI3Kβ in myeloid cells
Authors: Houslay Daniel M. , Anderson Karen E. , Chessa Tamara , Kulkarni Suhasini , Fritsch Ralph , Downward Julian , Backer Jonathan M. , Stephens Len R. , Hawkins Phillip T.
Published: August 2016

PI3Kβ mediates synergistic signaling upon costimulation of GPCRs and receptor tyrosine kinases in immune cells.
Paper of note in
Science Translational Medicine
Authors: Ferrarelli Leslie K.
Published: August 2016

This week’s article describes a less toxic approach to deplete stem cells from bone marrow to enable transplantation.
Papers of note in
Science
Authors: VanHook Annalisa M.
Published: August 2016

This week’s articles offer insights into the gating mechanism of a voltage-sensitive potassium channel and how sleep deprivation and circadian rhythms combine to affect brain activity.
New connections: Regulating transporters
Authors: Gough Nancy R.
Published: August 2016

Bacteria, plants, and animals rely on proper regulation of transporters for health and survival in changing conditions.
Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of the β-Lactamase Inhibitor Vaborbactam (RPX7009) in Healthy Adult Subjects
Authors: Griffith David C. , Loutit Jeffery S. , Morgan Elizabeth E. , Durso Stephanie , Dudley Michael N.
Published: August 2016

Vaborbactam (formerly RPX7009) is a member of a new class of β-lactamase inhibitor with pharmacokinetic properties similar to those of many β-lactams, including carbapenems. The pharmacokinetics and safety of vaborbactam were evaluated in 80 healthy adult subjects in a first-in-human randomized, placebo-controlled, double-blind, sequential single- and multiple-ascending-dose study. A total of 10 dose cohorts were enrolled in the study, with 6 subjects randomized to receive 250 to 2,000 mg of vaborbactam and 2 subjects randomized to receive placebo in each cohort. Maximum concentrations for vaborbactam were achieved at the end of the 3-h infusion. Vaborbactam exposure (
C
max
and area under the concentration-time curve [AUC]) increased in a dose-proportional manner following multiple doses. There was no evidence of accumulation with multiple doses, consistent with the terminal half-life of ∼2 h. Both the volume of distribution (
V
ss
) and plasma clearance were independent of dose. For the 2,000-mg dose, the plasma clearance was 0.17 ± 0.03 liters/h, the AUC from 0 h to infinity (AUC
0–∞
) was 144.00 ± 13.90 mg · h/liter, and the
V
ss
was 21.80 ± 2.26 mg · h/liter. Urinary recovery was 80% or greater over 48 h across all dose groups. No subjects discontinued the study due to adverse events (AEs), and no serious AEs (SAEs) were observed. All AEs were mild to moderate and similar among the vaborbactam- and placebo-treated subjects, with mild lethargy as the only unique AE reported with the high dose of vaborbactam. Overall, this study revealed the safety, tolerability, and pharmacokinetic profile of vaborbactam and formed the basis for advancement into patient studies in combination with meropenem, including treatment of patients with carbapenem-resistant
Enterobacteriaceae
(CRE) infections. (This study is registered at ClinicalTrials.gov under identifier NCT01751269.)
A Novel RNase 3/ECP Peptide for Pseudomonas aeruginosa Biofilm Eradication That Combines Antimicrobial, Lipopolysaccharide Binding, and Cell-Agglutinating Activities
Authors: Pulido David , Prats-Ejarque Guillem , Villalba Clara , Albacar Marcel , González-López Juan J. , Torrent Marc , Moussaoui Mohammed , Boix Ester
Published: August 2016

Eradication of established biofilm communities of pathogenic Gram-negative species is one of the pending challenges for the development of new antimicrobial agents. In particular,
Pseudomonas aeruginosa
is one of the main dreaded nosocomial species, with a tendency to form organized microbial communities that offer an enhanced resistance to conventional antibiotics. We describe here an engineered antimicrobial peptide (AMP) which combines bactericidal activity with a high bacterial cell agglutination and lipopolysaccharide (LPS) affinity. The RN3(5-17P22-36) peptide is a 30-mer derived from the eosinophil cationic protein (ECP), a host defense RNase secreted by eosinophils upon infection, with a wide spectrum of antipathogen activity. The protein displays high biofilm eradication activity that is not dependent on its RNase catalytic activity, as evaluated by using an active site-defective mutant. On the other hand, the peptide encompasses both the LPS-binding and aggregation-prone regions from the parental protein, which provide the appropriate structural features for the peptide's attachment to the bacterial exopolysaccharide layer and further improved removal of established biofilms. Moreover, the peptide's high cationicity and amphipathicity promote the cell membrane destabilization action. The results are also compared side by side with other reported AMPs effective against either planktonic and/or biofilm forms of
Pseudomonas aeruginosa
strain PAO1. The ECP and its derived peptide are unique in combining high bactericidal potency and cell agglutination activity, achieving effective biofilm eradication at a low micromolar range. We conclude that the designed RN3(5-17P22-36) peptide is a promising lead candidate against Gram-negative biofilms.