bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of atorvastatin on haemostatic parameters in apparently healthy dogs
Authors: Bonaparte A. , Tansey C. , Wiebe M. , Espinoza H. E. , Patlogar J. E. , Murphy L. A. , Nakamura R. K.
Published: May 2019

Objective

To determine the effect of atorvastatin on haemostatic parameters as measured by prothrombin time, activated partial thromboplastin time and thromboelastography in apparently healthy dogs administered 2 mg/kg orally once daily for 1 week.

Materials and Methods

Prospective study of 20 apparently healthy client‐owned dogs at a small animal specialty hospital. Dogs had a baseline complete blood count, serum chemistry profile, fibrinogen, platelet count, prothrombin time, activated partial thromboplastin time and thromboelastography performed. Each dog was then administered approximately 2 mg/kg of atorvastatin orally once daily for 1 week, and the laboratory tests were repeated. Adverse effects attributed to atorvastatin were recorded.

Results

All 20 enrolled dogs completed the study. Dogs received a median dose of 2.06 mg/kg (range 1.94 to 2.44 mg/kg) atorvastatin once daily, which was associated with a significant increase in pulse rate, mean corpuscular haemoglobin concentration, albumin and a significant decrease in mean corpuscular volume, cholesterol and lipase values compared with baseline. On thromboelastography, there was a significant increase in maximum amplitude, G, coagulation index, amplitude at 30 minutes, amplitude at 60 minutes and significant decrease in percentage of clot lysed at 30 minutes and percentage of clot lysed at 60 minutes values compared with baseline. Six dogs had a noticeable increase in appetite.

Clinical Significance

The results of this study suggest that atorvastatin may produce a procoagulant effect in dogs, although the clinical significance is unclear. Polyphagia was the most commonly reported adverse effect.
The Study of Heritage Language Development From a Bilingualism and Social Justice Perspective
Authors: Ortega Lourdes
Published: May 2019

Using the lenses of bilingualism and social justice, I reflect on relevant conceptual and methodological issues encountered in the study of the linguistic development of heritage language speakers. Themes examined include the early but varying timing of heritage language learning; the surrounding linguistic environment, including the link between parental input and linguistic outcomes and heritage language speakers’ bilingualism, multilingualism, and multilectalism; the framing of literacy in the minority language; and the unique and language‐shaping experience of minoritization, often an outcome of immigration. I argue that bilingualism is gradient and that better measurement of relevant variables—particularly those related to timing, input/exposure, and literacy—can invigorate the study of heritage language development and make new and more robust insights possible. I propose that heritage speakers and their languages must be understood as connected to minoritized communities and to the experience of inequitable multilingualism.
Saussurea balangshanensis sp. nov. (Asteraceae), from the Hengduan Mountains region, SW China
Authors: Zhang Yazhou , Tang Rong , Huang Xianhan , Sun Wenguang , Ma Xiangguang , Sun Hang
Published: May 2019

Saussurea balangshanensis, based on populations from Balang Mountain in the Hengduan Mountains region, SW China, is described and illustrated as a new species of Asteraceae. It can be distinguished from other species in Saussurea by its concolorous leaves, swollen and hollow upper stems, articulate hairs and stipitate glandular hairs, laciniate margins of uppermost stem leaves, numerous and sessile capitula, and narrow involucre. Based on nucleotide sequence data from the internal transcribed spacer (ITS), phylogenetic analyses also support the recognition of these populations as representing a new species. The new species is known only from a single location in Balang Mountain, at elevations of 4500–4700 m. Its habitat can be easily disturbed or destroyed by a tourist arterial highway and the over grazing. We propose that the species should be listed as Critically Endangered based on the International Union for Conservation of Nature Red List Categories and Criteria B2a.
Crinum reddyi sp. nov. (Amaryllidaceae) from Gujarat, India
Authors: Patel Mitesh , Patel Harshil
Published: May 2019

We here describe a new species of Crinum (Amaryllidaceae) from marshy areas along the Gira river, southern Gujarat, India. It superficially resembles C. solapurense but differs in having spherical or round, cremish white, tunicate bulbs, 10–17 distichous to sub distichous, canaliculated leaves, shorter, yellowish green peduncles (35–60 cm long), fewer flowers (up to 16), 6–12 capsules per infructscence, 4–7, chlorophyllous, rugose seeds per capsule and mainly vegetative propagation.
Stem cells  from exfoliated  deciduous  teeth alleviate hyposalivation caused by Sjögren syndrome
Authors: Du Zhi‐Hao , Ding Chong , Zhang Qian , Zhang Yan , Ge Xi‐Yuan , Li Sheng‐Lin , Yu Guang‐Yan
Published: May 2019

Objectives

To evaluate the effect of stem cells  from  exfoliated  deciduous  teeth on the hyposalivation caused by Sjögren syndrome (SS) and investigate the mechanism.

Methods

Stem cells were injected into the tail veins of non‐obese diabetic mice, the animal model of SS. The saliva flow was measured after pilocarpine intraperitoneal injection. Apoptosis and autophagy were evaluated by TUNEL and Western blot. Lymphocyte proportions were detected by flow cytometer.

Results

Fluid secretion was decreased in 21‐week‐old mice. Stem cell treatment increased fluid secretion, alleviated inflammation in the submandibular glands and reduced inflammatory cytokine levels in the serum, submandibular glands and saliva. Stem cells decreased the apoptotic cell number and the expressions of ATG5 and Beclin‐1 in the submandibular glands. Stem cells have no effect on other organs. Furthermore, the infused stem cells migrated to the spleen and liver, not the submandibular gland. Stem cells directed T cells towards Treg cells and suppressed Th1 and Tfh cells in spleen lymphocytes.

Conclusion

Stem cells  from  exfoliated  deciduous  teeth alleviate the hyposalivation caused by SS via decreasing the inflammatory cytokines, regulating the inflammatory microenvironment and decreasing the apoptosis and autophagy. The stem cells regulated in T‐cell differentiation are involved in the immunomodulatory effects.
Reproducibility of acute pulmonary vein isolation guided by the ablation index
Authors: Solimene Francesco , Lepillier Antoine , De Ruvo Ermenegildo , Scaglione Marco , Anselmino Matteo , Sebag Frederic A. , Pecora Domenico , Gallagher Mark M. , Rillo Mariano , Viola Graziana , Rossi Luca , De Santis Valerio , Landolina Maurizio , Castro Antonello , Grimaldi Massimo , Badenco Nicolas , Del Greco Maurizio , De Simone Antonio , Bertaglia Emanuele , Stabile Giuseppe
Published: May 2019

Background

Atrial fibrillation (AF) ablation outcome is still operator dependent. Ablation Index (AI) is a new lesion quality marker that has been demonstrated to allow acute durable pulmonary vein (PV) isolation followed by a high single‐procedure arrhythmia‐free survival.

This prospective, multicenter study was designed to evaluate the reproducibility of acute PV isolation guided by the AI.

Methods

A total of 490 consecutive patients with paroxysmal (80.4%) and persistent AF underwent first time PV encircling and were divided in four study groups according to operator preference in choosing the ablation catheter (a contact force [ST] or contact force surround flow [STSF] catheter) and the AI setting (330 at posterior and 450 at anterior wall or 380 at posterior and 500 at anterior wall). Radiofrequency was delivered targeting interlesion distance ≤6 mm.

Results

The rate of first‐pass PV isolation (ST330 90 ± 16%, ST380 87 ± 19%, STSF330 90 ± 17%, STSF380 91 ± 15%, P = .585) was similar among the four study groups, whereas procedure (ST330 129 ± 44 minutes, ST380 144 ± 44 minutes, STSF330 120 ± 72 minutes, STSF380 125 ± 73 minutes, P < .001) and fluoroscopy time (ST330 542 ± 285 seconds, ST380 540 ± 416 seconds, STSF330 257 ± 356 seconds, STSF380 379 ± 454 seconds, P < 0.001) significantly differed. The difference in the rate of first‐pass isolation was not statistical different (P = .06) among the 12 operators that performed at least 15 procedures.

Conclusions

An ablation protocol respecting strict criteria for contiguity and quality lesion results in high and comparable rate of acute PV isolation among operator performing ablation with different catheters, AI settings, procedure, and fluoroscopy times.
Acute outcome after a single cryoballoon ablation: Comparison between Arctic Front Advance and Arctic Front Advance PRO
Authors: Moltrasio Massimo , Sicuso Rita , Fassini Gaetano M. , Riva Stefania I. , Tundo Fabrizio , Dello Russo Antonio , Casella Michela , Majocchi Benedetta , Zucchetti Martina , Cellucci Selene , Tondo Claudio
Published: May 2019

Background

The novel fourth‐generation cryoballoon (CB4) potentially allows for enhanced catheter maneuverability and more frequent capture of pulmonary vein (PV) potentials which can be used to monitor real‐time PV isolation (PVI). The aim of our study is to compare the acute procedural endpoints between the CB4 and second‐generation cryoballoon (CB2).

Methods

A single‐center retrospective chart review was used to examine 50 consecutive patients with drug‐refractory atrial fibrillation undergoing CB4‐based PVI. Procedural data and acute success of these patients were compared to 50 propensity‐matched controls who underwent cryoballoon ablation procedure using CB2.

Results

Procedures performed with the CB4 showed significant shorter fluoroscopy time (14.8 ± 5.5 vs 18.0 ± 6.5 minutes, P = .04), shorter procedure time (58.3 ± 15.7 vs 65.3 ± 21 minutes, P = .13), and shorter total ablation time (10.8 ± 1.5 vs 13.8 ± 1.9 minutes, P = .42). The real‐time PVI visualization rate was 33.3% in the CB2 group and 74.7% in the CB4 group (P < .001). CB4 was correlated to significant increase of acute real‐time recordings with regard to all the single PV (left superior PV: 58% vs 84%, P = .02; left inferior PV: 26% vs 71%, P = .001; right superior PV 29% vs 61%, P = .01; and right inferior PV 19% vs 58%, P = .002).

Conclusion

The CB4 was more often able to capture real‐time recordings of PV potentials and the subsequent acute PV isolation.
Carbon assimilation in crops at high temperatures
Authors: Slattery Rebecca A. , Ort Donald R.
Published: May 2019

Global temperatures are rising, and higher rates of temperature increase are projected over land areas that encompass the globe's major agricultural regions. In addition to increased growing season temperatures, heat waves are predicted to become more common and severe. High temperatures can inhibit photosynthetic carbon gain of crop plants and thus threaten productivity, the effects of which may interact with other aspects of climate change. Here, we review the current literature assessing temperature effects on photosynthesis in key crops with special attention to field studies using crop canopy heating technology and in combination with other climate variables. We also discuss the biochemical reactions related to carbon fixation that may limit crop photosynthesis under warming temperatures and the current strategies for adaptation. Important progress has been made on several adaptation strategies demonstrating proof‐of‐concept for translating improved photosynthesis into higher yields. These are now poised to test in important food crops.
Modulation of K+translocation by AKT1 and AtHAK5 in Arabidopsis plants
Authors: Nieves‐Cordones Manuel , Lara Alberto , Ródenas Reyes , Amo Jesús , Rivero Rosa María , Martínez Vicente , Rubio Francisco
Published: May 2019

Root cells take up K+from the soil solution, and a fraction of the absorbed K+is translocated to the shoot after being loaded into xylem vessels. K+uptake and translocation are spatially separated processes. K+uptake occurs in the cortex and epidermis whereas K+translocation starts at the stele. Both uptake and translocation processes are expected to be linked, but the connection between them is not well characterized. Here, we studied K+uptake and translocation using Rb+as a tracer in wild‐typeArabidopsis thalianaand in T‐DNA insertion mutants in the K+uptake or translocation systems. The relative amount of translocated Rb+to the shoot was positively correlated with net Rb+uptake rates, and theakt1 athak5T‐DNA mutant plants were more efficient in their allocation of Rb+to shoots. Moreover, a mutation ofSKORand a reduced plant transpiration prevented the full upregulation ofAtHAK5gene expression and Rb+uptake in K+‐starved plants. Lastly, Rb+was found to be retrieved from root xylem vessels, with AKT1 playing a significant role in K+‐sufficient plants. Overall, our results suggest that K+uptake and translocation are tightly coordinated via signals that regulate the expression of K+transport systems.
The “one‐point method” for estimating maximum carboxylation capacity of photosynthesis: A cautionary tale
Authors: Burnett Angela C. , Davidson Kenneth J. , Serbin Shawn P. , Rogers Alistair
Published: May 2019

The maximum carboxylation capacity of Rubisco, Vc,max, is an important photosynthetic parameter that is key to accurate estimation of carbon assimilation. The gold‐standard technique for determining Vc,max is to derive Vc,max from the initial slope of an A–Ci curve (the response of photosynthesis, A, to intercellular CO2 concentration, Ci). Accurate estimates of Vc,max derived from an alternative and rapid “one‐point” measurement of photosynthesis could greatly accelerate data collection and model parameterization. We evaluated the practical application of the one‐point method in six species measured under standard conditions (saturating irradiance and 400 μmol CO2 mol−1) and under conditions that would increase the likelihood for successful estimation of Vc,max: (a) ensuring Rubisco‐limited A by measuring at 300 μmol CO2 mol−1 and (b) allowing time for acclimation to saturating irradiance prior to measurement. The one‐point method significantly underestimated Vc,max in four of the six species, providing estimates 21%–32% below fitted values. We identified ribulose‐1,5‐bisphosphate‐limited A, light acclimation, and the use of an assumed respiration rate as factors that limited the effective use of the one‐point method to accurately estimate Vc,max. We conclude that the one‐point method requires a species‐specific understanding of its application, is often unsuccessful, and must be used with caution.
Relationship between parenting stress and children's behavioral characteristics in Japan
Authors: Tokunaga Akiko , Iwanaga Ryoichiro , Yamanishi Yoko , Higashionna Takuya , Tanaka Koji , Nakane Hideyuki , Tanaka Goro
Published: May 2019

Background

The evaluation of a child tends to differ between the mother and father regardless of whether the child has a disability or not, although parents have key information about the behavioral characteristics of the child. The number of reports in Japan, however, is limited. We, therefore, investigated the relationship between the parenting stress experienced by parents of non‐clinical preschool children and the children's behavioral characteristics.

Method

The subjects were 83 pairs of mothers and fathers with non‐clinical children in kindergarten and nursery school (average age, 59.1 ± 13.0 months; 36 boys, 47 girls). The study was conducted using the Parenting Stress Index–Short Form (PSI‐SF) and the Strengths and Difficulties Questionnaire (SDQ).

Results

There was no difference in the PSI‐SF scores between mothers and fathers, but hyperactivity/inattention, peer relationship problems, and the total score of the SDQ were significantly higher in fathers. On multiple regression analysis, parenting stress experienced by fathers was significantly related to hyperactivity/inattention, while parenting stress experienced by mothers was significantly related to peer relationship problems and emotional symptoms.

Conclusion

Children's behavioral characteristics related to parenting stress differ between mothers and fathers.
Direct seeding and outplantings in drylands of Argentinean Patagonia: estimated costs, and prospects for large‐scale restoration and rehabilitation
Authors: Pérez Daniel R. , González Florencia , Ceballos Cristian , Oneto María E. , Aronson James
Published: May 2019

In large areas of the world that are deeply scarred by desertification and hampered by low capacity for natural regeneration, the scaling up of ecological restoration and rehabilitation can be achieved only if it is low in cost with high return on investment, and shows promise of providing long‐lasting social‐economic as well as ecological benefits. In the Monte Austral region of Patagonia Argentina, concerted efforts are underway to facilitate scaling up of ecological restoration and rehabilitation practices. Here, we evaluate financial costs and preliminary results of direct seeding as compared to outplanting of nursery‐grown seedlings of three native species (Atriplex lampa, Senecio subulatus var. subulatus, and Hyalis argentea var. latisquama) considered to be high‐priority dryland framework species. Comparative success is expressed in terms of plant survival and in monetary terms. The three candidate species showed low survival rates, ranging from 4.3 to 22.3%, after the first summer following direct seeding. In contrast, survival rates for planted seedlings of the same three taxa varied between 84 and 91%, after the first summer following reintroduction. However, cost of direct seeding varied between 1,693 and 1,772 US$ less per hectare, that is, 64% less than the cost of outplanting nursery seedlings. Therefore, in the search for ways to scale up ecological restoration and rehabilitation in drylands, direct seeding should receive more attention. We discuss the social and ecological perspectives and the way forward for direct seeding techniques in Patagonia. We also consider how costs could be reduced and effectiveness improved in large‐scale efforts.
Living Conditions and Basic Needs: Evidence from African Countries
Authors: Clark Andrew E. , D'Ambrosio Conchita
Published: May 2019

We here use five rounds of Afrobarometer data covering more than 100,000 individuals over the 2004–2016 period to explore the link between individual self‐reported measures of living conditions and access to four basic needs. We not only consider own access to these needs, but also various indices of their deprivation, satisfaction and inequality. We find some evidence of comparisons to those who are better off and to those who are worse off, in terms of access to basic needs, in the evaluation of current living conditions. Overall, however, subjective living conditions are mostly absolute in African countries. There is notable heterogeneity by level of development, with the effect of lack of access to basic needs being more pronounced in poorer countries. Equally, comparisons to the better off are associated with better living conditions in poorer countries, suggesting the existence of a tunnel effect: this latter disappears with economic development.
Assessment of physical functioning in the clinical care of the patient with advanced kidney disease
Authors: Roshanravan Baback , Patel Kushang V.
Published: May 2019

Maintenance of independent living is the top health priority among patients with advanced chronic kidney disease (CKD). Mobility limitation is often the first sign of functional limitation leading to loss of independence. Regular assessments of physical capacity can help provide kidney health providers identify patients at risk of frailty and other adverse health‐related outcomes that contribute to the loss of functional independence. These physical capacities can be measured with commonly used self‐reported measures of physical function or by objective physical performance testing. The current review describes commonly used assessments of self‐reported physical function and physical performance. First, we describe the disablement process and how these assessments can be performed with commonly used quality of life instruments measuring self‐reported physical function or objective physical performance tests. Second, we identify the determinants and correlates of self‐reported physical function and physical performance and their contribution to the frailty phenotype. Third, we describe the association of physical capacities with clinical outcomes. We conclude with on possible approach to identifying and intervening on persons with CKD at high risk of functional decline.
Effect of exercise training on heart rate variability in patients with obstructive sleep apnea: A randomized controlled trial
Authors: Berger Mathieu , Raffin Jérémy , Pichot Vincent , Hupin David , Garet Martin , Labeix Pierre , Costes Frédéric , Barthélémy Jean‐Claude , Roche Frédéric
Published: May 2019

While obstructive sleep apnea (OSA) increases chemoreflex, leading to an autonomic dysfunction in the long term, no studies have yet assessed the potential benefit of exercise on cardiac autonomic activity in these patients. The aim of this study was to evaluate potential improvement in cardiac autonomic function (CAF) measured through heart rate variability (HRV) after a 9‐month physical activity program in patients with OSA. Seventy‐four patients with moderate OSA, aged 40‐80 years, were randomly assigned to an exercise group (n = 36, 3 × 1 h/wk) or a control group (n = 38) during 9 months. Linear and nonlinear HRV parameters were measured during night using a Holter ECG. After 9 months, mean R‐R intervals increased in the exercise group without any changes in HRV parameters, while controls decreased global (standard deviation of normal‐to‐normal intervals, total power) and parasympathetic (root mean square successive difference of N‐Ns, very low frequency, high frequency, and standard deviation of the instantaneous beat‐to‐beat variability) indices of HRV (P < 0.05 for all). Significant correlations with moderate effect size were found between changes in apnea severity and changes in R‐R intervals (P < 0.05). Improvement in moderate‐to‐vigorous physical activity was also correlated to improvement in nocturnal oxygen parameters (P < 0.05). In conclusion, supervised community physical activity may prevent a decline in nighttime CAF observed in nontreated community‐dwelling patients with moderate OSA over a 9‐month period. Thus, beyond apnea‐hypopnea index improvement, exercise may be cardioprotective in OSA patients through bradycardia, CAF preservation, and VO2peak increase.
Prevalence and predictors of dropout from high‐intensity interval training in sedentary individuals: A meta‐analysis
Authors: Reljic Dejan , Lampe David , Wolf Franziska , Zopf Yurdagül , Herrmann Hans Joachim , Fischer Joachim
Published: May 2019

Recent evidence suggests that high‐intensity interval training (HIIT) is an effective method to improve fitness and various health markers. However, the tolerability and acceptability of HIIT among sedentary individuals is currently controversially discussed. Therefore, our objective was to investigate the prevalence and predictors of dropout among sedentary individuals in HIIT‐based exercise interventions. MEDLINE/PubMed, SPORTDiscus, and Web of Science were searched systematically for relevant articles until 06/2018. Studies included were required to (a) be written in English, (b) include sedentary healthy adults, (c) use some form of HIIT without any complementary intervention, (d) last ≥4 weeks, (e) report detailed description of the applied HIIT protocol, and (f) report data that allow calculation of a dropout rate. Fifty‐five studies reporting results from 67 HIIT interventions with 1318 participants met the eligibility criteria. The trim and fill adjusted pooled dropout rate across all interventions was 17.6% (95% confidence interval 14.2‐21.5%). Dropout rates were significantly lower in cycling‐based interventions compared with studies using running/walking as exercise modality (P < 0.001). Longer session time (β = 0.02, P < 0.05), higher time effort/week (β = 0.005, P < 0.05), and overall time effort/intervention (β = 0.0003, P < 0.05) predicted greater dropout. Exercise intensity was not related to dropout. Our data suggest that HIIT‐based interventions are tolerable and acceptable for previously sedentary individuals, exhibiting generally lower dropout rates than commonly reported for traditional exercise programs. Given the association between HIIT volume and dropouts, future studies should further focus on identifying the minimally effective dose of practical HIIT for improving health status. Such efforts would be important to increase implementation and public health impact of HIIT.
Reassembling the Rural: Socio‐Economic Dynamics, Inequalities and Resilience in Crisis‐Stricken Rural Greece
Authors: Papadopoulos Apostolos G. , Fratsea Loukia‐Maria , Karanikolas Pavlos , Zografakis Stavros
Published: May 2019

Rural areas are places where various social groups live either permanently or seasonally. The mobilities and immobilities of these groups are related to their differential resources. The vast impact of the financial crisis on Greece relates to the major decline of its GDP and enormous increase in unemployment. The article aims to shed light on the complexities of social marginalisation and social exclusion in rural Greece, but also, and more importantly, to theorise the coping mechanisms and strategies by those affected and build upon the experiences of rural areas during the prolonged economic crisis. Population dynamics and the various social and spatial mobilities in rural areas provide the baseline for tracing rural complexities and theorising the emergent coping strategies. The concepts of rural cosmopolitanism and resilience are used to unpack the complexities of marginalisation and social exclusion in rural Greece. A brief reference to the statistical data resolves the apparent controversies related to the changing regional and local geography of poverty and social exclusion in Greece during the crisis. The more focused empirical findings, illustrated in the form of two island areas, illustrate the various coping mechanisms and strategies that are emerging in rural Greece.
Characterization of the novel KIR2DL4*037 allele identified in a Chinese Hani individual
Authors: Su Pincan , Yang Tonghua , Ma Haili , Zhang Guobin , Deng Zhi‐Hui
Published: May 2019

The novel KIR2DL4*037 allele differs from the closest allele KIR2DL4*00501 by a single missense mutation.
Effects of continuous positive airway pressure on respiratory function in sedated foals
Authors: Raidal Sharanne L. , McKean Rosemary , Ellul Paula A. , Nielsen Sharon G. , Quinn Christopher T.
Published: May 2019

Objective

To characterize the effects of continuous positive airway pressure (CPAP) delivered by a commercial human CPAP device on respiratory function in foals with pharmacologically induced respiratory suppression.

Design

Prospective randomized, cross‐over study comparing CPAP with spontaneous respiration and oxygen insufflation.

Setting

University veterinary teaching hospital.

Animals

Twelve foals born in consecutive seasons from a university teaching herd.

Interventions

Foals were randomized to receive 10 minutes of respiratory support by mask oxygen supplementation or CPAP as a first treatment after induction of respiratory depression by intravenous administration of xylazine and fentanyl. Each foal received the alternate treatment after 10 minutes of breathing ambient air, and the procedure was repeated after 48 hours with treatment order reversed.

Measurements and main results

The administration of xylazine and fentanyl by bolus or continuous infusion reliably induced reversible respiratory suppression and recumbency. CPAP was associated with comparable increase in PaO2relative to mask oxygen supplementation, but with lower respiratory rate, increased oxygen extraction and increased carbon dioxide elimination. Mild increase in PaCO2was observed during CPAP and O2supplementation. Expiratory time increased and peak expiratory flow decreased during CPAP.

Conclusions

Findings of the study suggest that CPAP might represent a method for improved respiratory support compared to O2insufflation due to increased respiratory efficiency. Care must be taken in extrapolation of these findings from foals with pharmacologically induced respiratory compromise to foals with clinical respiratory disease, and further investigation is required to better characterize the cause and impact of marginal hypercapnia observed in these studies.
Long‐term outcomes of dogs undergoing surgical resection of mast cell tumors and soft tissue sarcomas: A prospective 2‐year‐long study
Authors: Milovancev Milan , Townsend Katy L. , Tuohy Joanne L. , Gorman Elena , Bracha Shay , Curran Kaitlin M. , Russell Duncan S.
Published: May 2019

Objective

Report clinical outcomes of dogs with surgically excised mast cell tumors (MCT) and soft tissue sarcomas (STS).

Study design

Prospective clinical study.

Sample population

Fifty‐three dogs with 52 MCT (50 low grade, 2 high grade) and 19 STS (12 grade I, 6 grade II, 1 grade III).

Methods

All dogs were examined at 3, 6, 12, 18, and 24 months postoperatively, with cytologic or histopathologic evaluation of suspected local recurrences. Dogs euthanized because of study tumor‐related causes underwent necropsy.

Results

Median intraoperative margins were 20 mm and 30 mm wide for MCT and STS, respectively, with 1 fascial plane resected en bloc. The narrowest histologic tumor‐free margins measured <1 mm in 21 of 52 (40%) MCT and 7 of 19 (37%) STS. All dogs were followed for 24 months. Two of 50 (4%) low‐grade MCT were diagnosed, with local recurrence 181 and 265 days postoperatively. Two of 36 (6%) dogs with low‐grade MCT developed visceral metastasis 181 and 730 days postoperatively. One of 2 dogs with high‐grade MCT developed local recurrence 115 days postoperatively. No local recurrence or metastasis was diagnosed after excision of 19 STS.

Conclusion

Local recurrence rates among predominantly low‐ to intermediate‐grade MCT and STS were low, despite a high prevalence of histologic tumor‐free margins <1 mm. Surgical recommendations for high‐grade tumors cannot be extrapolated from this population.

Clinical significance

Surgeons should seek to achieve microscopically complete excision for MCT and STS while minimizing patient morbidity and considering limitations of histopathology in predicting outcomes.
Cold‐induced cutaneous vasoconstriction in humans: Function, dysfunction and the distinctly counterproductive
Authors: Alba Billie K. , Castellani John W. , Charkoudian Nisha
Published: May 2019

New Findings

What is the topic of this review?

This review presents an update and synthesis of normal mechanisms of human cutaneous vasoconstriction in response to cold stress. It then discusses conditions in which cutaneous vasoconstrictor responses are excessive or insufficient and cases in which cold‐induced vasoconstrictor responses become counter to maintaining thermal and haemodynamic homeostasis.

What advances does it highlight?

The review highlights our current understanding of the mechanisms that mediate alterations in cold‐induced cutaneous vasoconstriction in pathology and environmental extremes, which has important clinical implications for preventing cold‐ and cardiovascular‐related deaths.

In humans, cold‐induced peripheral vasoconstriction is an essential element of body temperature regulation. Given that the thermoregulatory system responds rapidly to changes in skin temperature, sympathetically mediated cutaneous vasoconstriction represents a crucial ‘first line of defense’ against excessive reduction in body temperature. Sympathetic noradrenergic vasoconstrictor nerves cause a rapid decrease in skin blood flow, thus increasing the insulative capacity of the skin and decreasing heat loss from the body. Small changes in the activity of these nerves are also responsible for the subtle changes in skin blood flow that occur with normal daily activities or minor changes in environmental temperature. With ageing, hypertension and other conditions, the cutaneous reflex vasoconstrictor response can become excessive or insufficient. Healthy older adults have impaired reflex vasoconstriction, which may result in an impaired ability to defend body temperature in some circumstances. Hypertension is associated with augmented vasoconstriction, which could have pathological implications for left ventricular afterload in individuals already at risk for cardiovascular events. Finally, in some cases, the reflex vasoconstrictor response becomes distinctly counterproductive to its own goals of maintaining cardiovascular and thermoregulatory homeostasis. Examples include Raynaud's phenomenon, in which exaggerated vasoconstriction can produce ischaemia in the periphery, and the cutaneous vasoconstrictor response to therapeutic body cooling in severe hyperthermia, which can limit the heat exchange necessary to prevent serious heat illness.
Spinal Balance/Alignment—Clinical Relevance and Biomechanics
Authors: Shah Anoli , Lemans Justin V. C. , Zavatsky Joseph , Agarwal Aakash , Kruyt Moyo C. , Matsumoto Koji , Serhan Hassan , Agarwal Anand , Goel Vijay K.
Published: May 2019

In the anatomy of a normal spine, due to the curvatures in various regions, the C7 plumb line (C7PL) passes through the sacrum so that the head is centered over the pelvic-ball and socket hip and ankle joints. A failure to recognize malalignment in the sagittal plane can affect the patient's activity as well as social interaction due to deficient forward gaze. The sagittal balance configuration leads to the body undertaking the least muscular activities as possible necessary to maintain spinal balance. Global sagittal imbalance is energy consuming and often results in painful compensatory mechanisms that in turn negatively influence the patient's quality of life, self-image, and social interaction due to inability to maintain a horizontal gaze. Deformity, scoliosis, kyphosis, trauma, and/or surgery are some ways that this optimal configuration can be disturbed, thus requiring higher muscular activity to maintain posture and balance. Several parameters such as the thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), and hip and leg positions influence the sagittal balance and thus the optimal configuration of spinal alignment. This review examines the clinical and biomechanical aspects of spinal imbalance, and the biomechanics of spinal balance as dictated by deformities—ankylosing spondylitis (AS), scoliosis and kyphosis; surgical corrections—pedicle subtraction osteotomies (PSO), long segment stabilizations, and consequent postural complications like proximal and distal junctional kyphosis. The study of the biomechanics involved in spinal imbalance is relatively new and thus the literature is rather sparse. This review suggests several potential research topics in the area of spinal biomechanics.
An Investigation Into the Challenges of Using Metal Additive Manufacturing for the Production of Patient-Specific Aneurysm Clips
Authors: Walker Brandon J. , Cox Benjamin L. , Cikla Ulas , de Bellefon Gabriel Meric , Rankouhi Behzad , Steiner Leo J. , Mahadumrongkul Puwadej , Petry George , Thevamaran Mythili , Swader Rob , Kuo John S. , Suresh Krishnan , Thoma Dan , Eliceiri Kevin W.
Published: May 2019

Cerebral aneurysm clips are biomedical implants applied by neurosurgeons to re-approximate arterial vessel walls and prevent catastrophic aneurysmal hemorrhages in patients. Current methods of aneurysm clip production are labor intensive and time-consuming, leading to high costs per implant and limited variability in clip morphology. Metal additive manufacturing is investigated as an alternative to traditional manufacturing methods that may enable production of patient-specific aneurysm clips to account for variations in individual vascular anatomy and possibly reduce surgical complication risks. Relevant challenges to metal additive manufacturing are investigated for biomedical implants, including material choice, design limitations, postprocessing, printed material properties, and combined production methods. Initial experiments with additive manufacturing of 316 L stainless steel aneurysm clips are carried out on a selective laser melting (SLM) system. The dimensions of the printed clips were found to be within 0.5% of the dimensions of the designed clips. Hardness and density of the printed clips (213 ± 7 HV1 and 7.9 g/cc, respectively) were very close to reported values for 316 L stainless steel, as expected. No ferrite and minimal porosity is observed in a cross section of a printed clip, with some anisotropy in the grain orientation. A clamping force of approximately 1 N is measured with a clip separation of 1.5 mm. Metal additive manufacturing shows promise for use in the creation of custom aneurysm clips, but some of the challenges discussed will need to be addressed before clinical use is possible.
“Mes Que un Club” and an Empty Camp Nou: A Case Study of Strategic Ambiguity and Catalan Nationalism at Football Club Barcelona
Authors: Kassing Jeffrey W.
Published: May 2019

Football Club Barcelona represents a successful modern sport entity with global influence and a celebrated past. It also has an undeniable connection to the region of Catalonia and has become in many ways a vehicle mobilized in the resurgent movement to seek Catalan independence from Spain. This case study considers how the strong and lasting link with Catalonia coupled with the club’s strategically ambiguous “mes que un club” (more than a club) motto combined to place the club in the difficult position of deciding to play a game in an empty stadium. The action, intended to be symbolic, proved questionable given the assorted stakeholders affected by the decision.
New clues to ancient water on Itokawa
Authors: Jin Ziliang , Bose Maitrayee
Published: May 2019

Itokawa contains Earth-like water.
Yam genomics supports West Africa as a major cradle of crop domestication
Authors: Scarcelli Nora , Cubry Philippe , Akakpo Roland , Thuillet Anne-Céline , Obidiegwu Jude , Baco Mohamed N. , Otoo Emmanuel , Sonké Bonaventure , Dansi Alexandre , Djedatin Gustave , Mariac Cédric , Couderc Marie , Causse Sandrine , Alix Karine , Chaïr Hâna , François Olivier , Vigouroux Yves
Published: May 2019

Yam, a tuber crop, was domesticated alongside some African cereals and defines a cradle of domestication in West Africa.
Chromatin three-dimensional interactions mediate genetic effects on gene expression
Authors: Delaneau O. , Zazhytska M. , Borel C. , Giannuzzi G. , Rey G. , Howald C. , Kumar S. , Ongen H. , Popadin K. , Marbach D. , Ambrosini G. , Bielser D. , Hacker D. , Romano L. , Ribaux P. , Wiederkehr M. , Falconnet E. , Bucher P. , Bergmann S. , Antonarakis S. E. , Reymond A. , Dermitzakis E. T.
Published: May 2019

Noncoding variation and gene expression

Natural genetic variation outside of protein coding regions affects multiple molecular phenotypes that can differ across individuals. To examine how genomic variation affects proximal (cis) or distal (trans) gene regulation, Delaneau
et al.
analyzed gene expression, chromatin, and the three-dimensional conformation of the genome. Clustering regulatory elements and activity across individuals reveals genomic structures termed cis-regulatory domains and trans-regulatory hubs that affect gene expression. Associations between these structures and genes within and across chromosomes contribute to links between noncoding genetic variation and gene expression.

Science
, this issue p.
eaat8266
Structural topology defines protective CD8
+
T cell epitopes in the HIV proteome
Authors: Gaiha Gaurav D. , Rossin Elizabeth J. , Urbach Jonathan , Landeros Christian , Collins David R. , Nwonu Chioma , Muzhingi Itai , Anahtar Melis N. , Waring Olivia M. , Piechocka-Trocha Alicja , Waring Michael , Worrall Daniel P. , Ghebremichael Musie S. , Newman Ruchi M. , Power Karen A. , Allen Todd M. , Chodosh James , Walker Bruce D.
Published: May 2019

Structure-based immunogen design

Vaccine design for highly mutable pathogens is hindered by a paucity of conserved immunogenic epitopes. Gaiha
et al.
employed a structure-based technique using network theory to assign scores to protein structure in order to infer mutational constraints (see the Perspective by McMichael and Carrington). The authors validated the method on proteins with published functional outcomes and then assessed mutational constraints within the HIV proteome. Highly networked residues strongly associated with immune control of HIV infection and may lead to protective immunogens for pathogens for which there is currently no efficient vaccine.

Science
, this issue p.
480
; see also p.
438
eIF2B-catalyzed nucleotide exchange and phosphoregulation by the integrated stress response
Authors: Kenner Lillian R. , Anand Aditya A. , Nguyen Henry C. , Myasnikov Alexander G. , Klose Carolin J. , McGeever Lea A. , Tsai Jordan C. , Miller-Vedam Lakshmi E. , Walter Peter , Frost Adam
Published: May 2019

Integrated stress response on the brain

During translation, regulation of protein synthesis by phosphorylation of eukaryotic translation initiation factor 2 (eIF2) is a common consequence of diverse stress stimuli, which leads to reprogramming of gene expression. This process, known as the integrated stress response, is one of the most fundamental mechanisms of translational control conserved throughout eukaryotes. It is also a promising therapeutic target in neurodegenerative diseases and traumatic brain injury. Kashiwagi
et al.
report the cryo–electron microscopy and crystal structures and Kenner
et al.
report the cryo–electron microscopy structure of the guanine nucleotide exchange factor eIF2B in complex with eIF2 or phosphorylated eIF2. The structures of the eIF2•eIF2B complex reveal that the single phosphorylation modification on eIF2 changes how eIF2 binds to eIF2B and locks this enzyme into an inhibited complex.

Science
, this issue p.
495
, p.
491
Architects of neuronal wiring
Authors: Falkner Susanne , Scheiffele Peter
Published: May 2019

Synapse formation is steered to neuronal subcompartments by molecular signals
Efficacy of Human Exposures of Gepotidacin (GSK2140944) against
Escherichia coli
in a Rat Pyelonephritis Model
Authors: Hoover Jennifer L. , Singley Christine M. , Elefante Philippa , Rittenhouse Stephen
Published: May 2019

Gepotidacin is a first-in-class triazaacenaphthylene antibacterial that inhibits bacterial type II topoisomerases and has
in vitro
activity against a range of bacterial pathogens, including
Escherichia coli
. Urinary tract infections often progress to pyelonephritis and are a worldwide problem due to the prevalence of multidrug-resistant
E. coli
strains.
A Multiprotein Complex Anchors Adhesive Holdfast at the Outer Membrane of Caulobacter crescentus
Authors: Sulkowski Nina I. , Hardy Gail G. , Brun Yves V. , Bharat Tanmay A. M.
Published: May 2019

Adhesion and biofilm formation are fundamental processes that accompany bacterial colonization of surfaces, which are of critical importance in many infections.
Caulobacter crescentus
biofilm formation proceeds via irreversible adhesion mediated by a polar polysaccharide called holdfast. Mechanistic and structural details of how the holdfast is secreted and anchored on cells are still lacking. Here, we have assigned the location and described the arrangement of the holdfast anchor complex. This work increases our knowledge of the relatively underexplored field of polysaccharide-mediated adhesion by identifying structural elements that anchor polysaccharides to the cell envelope, which is important in a variety of bacterial species.
Human Monoclonal Antibodies Potently Neutralize Zika Virus and Select for Escape Mutations on the Lateral Ridge of the Envelope Protein
Authors: Bailey Mark J. , Broecker Felix , Freyn Alec W. , Choi Angela , Brown Julia A. , Fedorova Nadia , Simon Viviana , Lim Jean K. , Evans Matthew J. , García-Sastre Adolfo , Palese Peter , Tan Gene S.
Published: May 2019

Zika virus (ZIKV) is a global health threat causing severe disease in humans, including microcephaly in newborns and Guillain-Barré syndrome in adults. Here, we analyzed the human monoclonal antibody response to acute ZIKV infection and found that neutralizing antibodies could not elicit Fc-mediated immune effector functions but could potentiate antibody-dependent enhancement of disease. We further identified critical epitopes involved with neutralization by generating and characterizing escape variants by whole-genome sequencing. We demonstrate that the lateral ridge region, particularly the S368 amino acid site, is critical for neutralization by domain III-specific antibodies.
Deposition of >3.7 Ga clay-rich strata of the Mawrth Vallis Group, Mars, in lacustrine, alluvial, and aeolian environments
Authors: Lowe Donald R. , Bishop Janice L. , Loizeau Damien , Wray James J. , Beyer Ross A.
Published: May 2019

The presence of abundant phyllosilicate minerals in Noachian (>3.7 Ga) rocks on Mars has been taken as evidence that liquid water was stable at or near the surface early in martian history. This study investigates some of these clay-rich strata exposed in crater rim and inverted terrain settings in the Mawrth Vallis region of Mars. In Muara crater the 200-m-thick, clay-rich Mawrth Vallis Group (MVG) is subdivided into five informal units numbered 1 (base) to 5 (top). Unit 1 consists of interbedded sedimentary and volcanic or volcaniclastic units showing weak Fe/Mg-smectite alteration deposited in a range of subaerial depositional settings. Above a major unconformity eroded on Unit 1, the dark-toned sediments of Unit 2 and lower Unit 3 are inferred to represent mainly wind-blown sand. These are widely interlayered with and draped by thin layers of light-toned sediment representing fine suspended-load aeolian silt and clay. These sediments show extensive Fe/Mg-smectite alteration, probably reflecting subaerial weathering. Upper Unit 3 and units 4 and 5 are composed of well-layered, fine-grained sediment dominated by Al-phyllosilicates, kaolinite, and hydrated silica. Deposition occurred in a large lake or arm of a martian sea. In the inverted terrain 100 km to the NE, Unit 4 shows very young slope failures suggesting that the clay-rich sediments today retain a significant component of water ice. The MVG provides evidence for the presence of large, persistent standing bodies of water on early Mars as well as a complex association of flanking shoreline, alluvial, and aeolian systems. Some of the clays, especially the Fe/Mg smectites in upper units 1 and 2 appear to have formed through subaerial weathering whereas the aluminosilicates, kaolinite, and hydrated silica of units 3, 4, and 5 formed mainly through alteration of fine sediment in subaqueous environments.