bluuebunny/crossref_metadata_2025 huggingface dataset:
Consumption of Fish and Shrimp from Southeast Louisiana Poses No Unacceptable Lifetime Cancer Risks Attributable to High‐Priority Polycyclic Aromatic Hydrocarbons
Authors: Wickliffe Jeffrey K. , Simon‐Friedt Bridget , Howard Jessi L. , Frahm Ericka , Meyer Buffy , Wilson Mark J. , Pangeni Deepa , Overton Edward B.
Published: March 2018

Following oil spills such as the Deepwater Horizon accident (DWH), contamination of seafood resources and possible increased health risks attributable to consumption of seafood in spill areas are major concerns. In this study, locally harvested finfish and shrimp were collected from research participants in southeast Louisiana and analyzed for polycyclic aromatic hydrocarbons (PAHs). PAHs are some of the most important chemicals of concern regarding oil‐spill‐contaminated seafood resources during and following oil spills. Some PAHs are considered carcinogens for risk assessment purposes, and currently, seven of these can be combined in lifetime cancer risk assessments using EPA approaches. Most PAHs were not detected in these samples (minimum detection limits ranged from 1.2 to 2.1 PPB) and of those that were detected, they were generally below 10 PPB. The pattern of detected PAHs suggested that the source of these chemicals in these seafood samples was not a result of direct contact with crude oil. Lifetime cancer risks were assessed using conservative assumptions and models in a probabilistic framework for the seven carcinogenic PAHs. Lifetime health risks modeled using this framework did not exceed a 1/10,000 cancer risk threshold. Conservative, health‐protective deterministic estimates of the levels of concern for PAH chemical concentration and seafood intake rates were above the concentrations and intake rates modeled under this probabilistic framework. Taken together, consumption of finfish and shrimp harvested from southeast Louisiana following the DWH does not pose unacceptable lifetime cancer risks from these seven carcinogenic PAHs even for the heaviest possible consumers.
Optimizing Natural Killer Cell Doses for Heterogeneous Cancer Patients on the Basis of Multiple Event Times
Authors: Lee Juhee , Thall Peter F. , Rezvani Katy
Published: March 2018

A sequentially adaptive Bayesian design is presented for a clinical trial of cord-blood-derived natural killer cells to treat severe haematologic malignancies. Given six prognostic subgroups defined by disease type and severity, the goal is to optimize cell dose in each subgroup. The trial has five co-primary outcomes: the times to severe toxicity, cytokine release syndrome, disease progression or response and death. The design assumes a multivariate Weibull regression model, with marginals depending on dose, subgroup and patient frailties that induce association between the event times. Utilities of all possible combinations of the non-fatal outcomes over the first 100 days following cell infusion are elicited, with posterior mean utility used as a criterion to optimize the dose. For each subgroup, the design stops accrual to doses having an unacceptably high death rate and at the end of the trial selects the optimal safe dose. A simulation study is presented to validate the design's safety, ability to identify optimal doses and robustness, and to compare it with a simplified design that ignores patient heterogeneity.
The participant roles of bullying in different grades: Prevalence and social status profiles
Authors: Pouwels J. Loes , van Noorden Tirza H. J. , Lansu Tessa A. M. , Cillessen Antonius H. N.
Published: March 2018

This study examined grade differences in the social status profiles and prevalence of bullying participant roles. Participants were 598 primary school students (grades 4–6), 545 students in the lower‐grades of secondary school (grades 7–8), and 1491 students in the upper‐grades of secondary school (grades 9–11). Students' participant roles, popularity, and social preference were measured with peer nominations. Bullies, assistants, and reinforcers (i.e., bullies/followers) were as popular as defenders in primary school, but more popular than defenders in secondary school. These differences depended on the gender of the reference group. Bullies/followers were more popular than defenders among other‐gender peers in the lower‐grades of secondary school but not among same‐gender peers. In the upper‐grades of secondary school, bullies/followers were more popular than defenders among all peers. Grade differences in social preference were small. The grade differences in popularity profiles of the roles were in line with grade differences in prevalence rates. Bully/follower roles were more common in secondary school than primary school among girls and the defender role was less common in secondary school among boys. This suggests that bully/follower roles are more rewarded with social status in secondary school than in primary school.
Relationship of hyaluronan and HYBID (KIAA1199) expression with roughness parameters of photoaged skin in Caucasian women
Authors: Yoshida H. , Komiya A. , Ohtsuki R. , Kusaka‐Kikushima A. , Sakai S. , Kawabata K. , Kobayashi M. , Nakamura S. , Nagaoka A. , Sayo T. , Okada Y. , Takahashi Y.
Published: March 2018

Background

Hyaluronan (HA) is an important constituent of extracellular matrix (ECM) in the skin, and HA degradation mediated by HYBID (KIAA1199) is suggested to be implicated in facial skin wrinkling in Japanese women. Ethnic difference in skin wrinkle formation is known between Caucasian and Japanese women, but no information is available for the relations of HA and HYBID expression levels with skin wrinkling in Caucasian women.

Methods

The skin surface roughness at the eye corner of the Caucasian female subjects was measured, and the skin specimens biopsied from the same areas were subjected to microarray gene analysis, HA staining, and immunohistochemistry for HYBID.

Results

Among the ECM genes and those related to ECM metabolism, only HYBID expression levels positively correlated with the skin roughness parameters. When the skin sample groups with high expression of HYBID or low expression of HYBID were compared, the HA staining intensity and the ratio of HYBID‐immunoreactive cells to total cells in the superficial dermis were significantly reduced and increased in the high‐HYBID‐expression group compared with the low‐HYBID‐expression group, respectively.

Conclusion

Our data suggest that like Japanese women, HYBID‐mediated reduction of HA in the superficial dermis is involved in the formation of wrinkles in Caucasian women.
Five‐year trends in perioperative red blood cell transfusion from index cases in five surgical specialties: 2011 to 2015
Authors: Mazzeffi Michael A. , See John M. , Williams Brittney , Richards Justin , Zimmerman Darin , Galvagno Samuel , Fontaine Magali , Tanaka Kenichi
Published: March 2018

BACKGROUND

Red blood cell (RBC) transfusion can be life‐saving; however, the risks of RBC transfusion have been increasingly recognized, and current guidelines recommend restrictive transfusion in most patients. We hypothesized that RBC transfusions are decreasing in surgical patients.

STUDY DESIGN AND METHODS

A retrospective review of the National Surgical Quality Improvement Program database was performed from 2011 to 2015. Index cases in five surgical specialties were studied: neurosurgery, thoracic surgery, gynecologic surgery, orthopedic surgery, and vascular surgery. Patient characteristics, preoperative laboratory values, and surgery details were compared between years. The study's primary outcome was perioperative RBC transfusion, which was compared over the 5‐year period for each specialty. Secondary outcomes were myocardial infarction and renal failure after surgery. In addition, trends in RBC transfusion between low‐risk and high‐risk patients and between emergency and elective surgery were examined.

RESULTS

RBC transfusion decreased in all surgical specialties except for thoracic and gynecologic surgery. RBC transfusion decreased substantially in orthopedic surgery, falling from 22.4% in 2011 to 6.3% in 2015 (p ≤ 0.0001). High‐risk patients had greater reductions in the receipt of RBC transfusion than low‐risk patients, and there were no increases in myocardial infarction or renal failure after surgery in any specialty.

CONCLUSION

RBC transfusion appears to be decreasing across multiple surgical specialties, with no apparent increase in myocardial infarctions or renal failure. This likely represents an important improvement in patient care. Continued efforts are needed to develop patient blood management programs and further reduce RBC transfusion.
How do we manufacture clinical‐grade interleukin‐15–stimulated natural killer cell products for cancer treatment?
Authors: Fernández Lucía , Leivas Alejandra , Valentín Jaime , Escudero Adela , Corral Dolores , de Paz Raquel , Vela Maria , Bueno David , Rodríguez Rebeca , Torres Juan Manuel , Díaz‐Almirón Mariana , López‐Collazo Eduardo , Martinez‐Lopez Joaquin , Pérez‐Martínez Antonio
Published: March 2018

BACKGROUND

Cancer immunotherapy involving natural killer (NK) cells has gained interest. Here we report two methods to obtain interleukin (IL)‐15–activated NK cells for clinical use.

STUDY DESIGN AND METHODS

IL‐15–activated NK cell products were obtained after 1) enrichment from healthy haploidentical donors' peripheral blood mononuclear cells (PBMNCs) collected by nonmobilized apheresis by a two‐step magnetic procedure, depletion of CD3+ cells followed by selection of CD56+ cells and ex vivo overnight stimulation with IL‐15 (NKIL15); and 2) expansion using the K562‐mb15‐41BBL cell line (NKAE), from autologous PBMNCs from patients with multiple myeloma or expansion from healthy haploidentical PBMNCs obtained from whole blood using the same previous cell line. We analyzed the NK cell recovery and expansion, T cell depletion, phenotype, cytotoxicity, safety, and genomic stability of two good manufacturing practices (GMP)–grade IL‐15–activated NK cell products.

RESULTS

The number of NK cells obtained from NKIL15 cell and NKAE cell products was similar; however, there were significantly fewer T cells in the NKIL15 cell product. The haploidentical NKAE cell product contained more T cells than the autologous NKAE cell product. The surface expression of the activating receptors CD69, CD25, natural killer group‐2 member D receptor, NKp44, NKp46, NKp30, and DNA accessory molecule 1 was up regulated in both NK cell products. NKIL15 cell and NKAE cell products had significantly higher lytic activity than unstimulated NK cells and showed no lytic activity against PBMNCs from healthy donors. No genetic alterations or potential oncogenic effects were found.

CONCLUSION

Different GMP‐grade procedures can be used to obtain large numbers of highly IL‐15–activated NK cells with extremely low T cell content for clinical use.
Long‐term social, economic and fiscal effects of immigration into the EU: The role of the integration policy
Authors: Kancs d'Artis , Lecca Patrizio
Published: March 2018

The issues of the forced migration on the one side and the integration of refugees in the EU society and labour markets on the other side are high on the policy agenda. Apart from humanitarian aspects, a sustainable integration of accepted asylum seekers is important also for social, economic, budgetary and other reasons. Although the potential socioeconomic consequences of accepted asylum seekers often are being discussed, little scientific evidence has supported the policy debate in the context of the current refugee crisis in the EU so far. This study attempts to shed light on the long‐run social, economic and budgetary effects of the rapidly increasing forced immigration into the EU by performing a holistic analysis of alternative refugee integration scenarios. Our simulation results suggest that, although the refugee integration, for example, by the providing language and professional training, is costly for the public budget, in the medium to long‐run, the social, economic and fiscal benefits may significantly outweigh the short‐run refugee integration costs. Depending on the integration policy scenario and policy financing method, the annual long‐run GDP effect would be 0.2%–1.6% above the baseline growth.
Treatment of spontaneous chronic corneal epithelial defects (SCCEDs) with diamond burr debridement vs combination diamond burr debridement and superficial grid keratotomy
Authors: Wu Doris , Smith Sara M. , M. Stine Jessica , M. Michau Tammy , Miller Thomas R. , Pederson Samantha L. , Freeman Kate S.
Published: March 2018

Objective

To evaluate the efficacy of diamond burr debridement (DBD) vs a combination of diamond burr debridement with superficial grid keratotomy (DBD+SGK) for the treatment of spontaneous chronic corneal epithelial defects (SCCEDs) in dogs.

Procedure

Medical records of dogs diagnosed with SCCEDs from three different institutions that received a DBD or DBD+SGK between 2003 and 2015 were reviewed. Age, breed, sex, history of a previous SCCED, procedures performed, time to healing, and complications were statistically analyzed.

Results

One hundred and ninety‐four dogs met the inclusion criteria. Eighty‐two of 106 eyes (77.4%) received a DBD and healed following the first treatment (13.3 ± 4.9 days to recheck, range 2‐27). Sixty‐eight of 88 eyes (77.3%) received a DBD+SGK and healed following the first treatment (15.4 ± 5.0 days to recheck, range 5‐45). No significant difference in healing outcome was found between the two treatments (P = 1). For SCCEDs that healed after a single treatment (n = 150), complications occurred in 13.3% (n = 20) of eyes with no difference in complications between the DBD and DBD+SGK groups (P = .86). Thirty‐five of 44 eyes (80.0%) healed after the second treatment (16 ± 8.2 days from second treatment to third visit, range 5‐47); nine of 44 eyes (20.0%) were not healed (12 ± 6.2 days from second treatment to third visit, range 5‐25). The second treatment method did not influence healing rates (P = .64).

Conclusions

DBD and DBD+SGK are equally effective treatment methods for canine SCCEDs. No differences in complication rates after one treatment were observed between DBD and DBD+SGK.
Utility of two‐view vs. three‐view abdominal radiography in canines presenting with acute abdominal signs
Authors: Mavromatis Marina V. , Solano Mauricio , Thelen Michael Y.
Published: March 2018

There are clear differences in the normal radiographic appearance of the abdominal organs between a left lateral vs. a right lateral view. While a few veterinary academic institutions have transitioned to a three‐view abdominal radiographic study protocol, obtaining only two views of the canine abdomen remains the current standard in veterinary medicine. In this combined retrospective and prospective, case‐controlled study, 48 canine patients presenting with signs of acute abdomen were recruited. Four board‐certified veterinary radiologists and four general practice veterinarians with greater than 3 years of experience in small animal practice were asked to determine if 10 predetermined findings were present within the set of images and if surgery was recommended based on those findings. Image readers were unaware of the clinical history. Three‐view studies did not yield statistically significantly greater accuracy than two‐view studies when evaluating all readers together. No statistically significant associations between the availability of the third view and increased accuracy or confidence were found in evaluations of general practitioners specifically. Evaluation of three‐view radiographic examination, as compared to two‐view examination, did not have perceived or statistically significantly increased diagnostic utility. Based on our findings, there is no statistically increased utility to justify a standard three‐view abdominal radiographic examination over a two‐view study for canines presenting with signs of acute abdomen.
Can camels disperse seeds of the invasive tree Prosopis juliflora?
Authors: Abbas A M , Mancilla‐Leytón J M , Castillo J M
Published: March 2018

Endozoochory has been recognised as the most important dispersal mechanism in invasive Prosopis species, because their sugary, tasty pods attract animals and because some of their seeds remain intact after passing through some animals' digestive systems. In this study, we evaluated the role of the camel (Camelus dromedarius) as a potential disperser of the seeds of invasive tree Prosopis juliflora. Four camels of similar weight (ca. 400 kg) and age (ca. 2 years) were each fed with 70 fruits (1000 seeds approximately) of P. juliflora, which were retrieved from the camels' dung at 24‐h intervals for 4 days. The seeds retrieved were tested for germination and viability, along with seeds not eaten by the camels, with and without pericarp. Less than 3% of the seeds eaten were retrieved from the camels' dung. Most of the seeds (74%) were retrieved between 24 and 72 h after ingestion. The passage through the camel gut significantly accelerated and increased seed germination of P. juliflora in comparison with uneaten seeds covered with pericarp (48–75% and 15% respectively). While gut passage liberated P. juliflora seeds from the pericarp, increasing and accelerating their germination, the viability of seeds which had not germinated after germination trials were decreased (ca. ~20%) relative to uneaten seeds that had also not germinated. Our results show that, despite the low recorded seed recovery, camels can potentially disperse seeds of P. juliflora, which is in line with field observation showing P. juliflora expansion along the camels' routes in Gebel Elba National Park, south‐east Egypt.
Floristic composition and species diversity of weed community after 10 years of different cropping systems and soil tillage in a Mediterranean environment
Authors: Campiglia E , Radicetti E , Mancinelli R
Published: March 2018

Sustainable cropping systems based on low inputs have received much attention, even if they may lead to the establishment of a competitive weed flora. This study, conducted from 2011 to 2014 in a Mediterranean environment, evaluated the changes in weed community composition in two cropping systems [conventional (CONV) and organic (ORG)] with different soil tillage [inversion tillage (IT) and non‐inversion tillage (NoIT)] in a wheat–tomato–chickpea rotation that began in 2000. The treatments were replicated three times according to a randomised complete block design. The organic system was managed according to EU regulations. Inversion tillage consisted of mouldboard ploughing to a depth of 30 cm, while NoIT consisted of subsoiling to a depth of 20 cm. Weed control was based on herbicide application in CONV and mechanical weeding in ORG. The organic non‐inversion system showed the highest weed biomass (134, 128 and 195 g dry matter (DM) m−2 in wheat, tomato and chickpea, respectively) and weed density (66, 77 and 76 plants m−2 in wheat, tomato and chickpea, respectively), as well as community richness. However, ORG always increased weed diversity, even if annual dicotyledon species were abundant in ORG‐IT and perennial dicotyledon species in ORG‐NoIT. The conventional system enhanced the relative frequency of both annual (CONV‐IT) and perennial (CONV‐NoIT) grasses. There was a negative correlation between density of perennial weeds and crop yield (r2 = 0.24, P < 0.001). Therefore, in the Mediterranean environment, combining organic practices with non‐inversion tillage could lead to the establishment of perennial weeds that are difficult to control, thus requiring specific weed management practices.
Toward multiplexed quantification of biomolecules on surfaces using time-of-flight secondary ion mass spectrometry
Authors: Wogelred Louise , Höök Fredrik , Agnarsson Björn , Sjövall Peter
Published: March 2018

Accurate detection and quantification of individual molecules is important for the development of improved diagnostic methods as well as biochemical characterization of disease progression and treatments. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is a surface analysis technique capable of imaging the distribution of specific molecules on surfaces with a high spatial resolution (<1 μm) and high sensitivity. ToF-SIMS is particularly suitable for detection of molecules up to ∼2 kDa, including lipids, whereas larger molecules, such as peptides and proteins, are fragmented during analysis, which makes them difficult to identify. In this study, an approach for extending the molecular detection capability of ToF-SIMS is presented, based on the specific binding of functionalized liposomes to molecular targets on the sample surface and subsequent detection of the liposomes by ToF-SIMS. Furthermore, by using different recognition elements conjugated to liposomes with different lipid compositions, simultaneous detection of different targets was accomplished. This multiplexing capability was investigated for two types of recognition elements (antibodies and cholera toxin) and for target molecules immobilized on surfaces using two frequently applied surface functionalization strategies: a supported lipid bilayer aimed to mimic a cell membrane and a polyethylene glycol modified surface, commonly employed in bioanalytical sensor applications. The efficacy of the conjugation protocols and the specificity of the recognition mechanism were confirmed using quartz crystal microbalance with dissipation monitoring, while fluorescence microscopy was used to validate the ToF-SIMS data and the reliability of the freeze-drying step required for ToF-SIMS analysis. The results demonstrated specific binding of the two types of liposomes to each target and showed a concentration-dependent binding to the targets on the different model surfaces. In particular, the possibility to use the contrasts in the mass spectra of SIMS to identify the concentration dependent coverage of different liposomes opens up new opportunities for multiplexed detection and quantification of molecules at biotechnology relevant interfaces.
Peak Age and Performance Progression in World-Class Track-and-Field Athletes
Authors: Haugen Thomas A. , Solberg Paul A. , Foster Carl , Morán-Navarro Ricardo , Breitschädel Felix , Hopkins Will G.
Published: March 2018

The aim of this study was to quantify peak age and improvements over the preceding years to peak age in elite athletic contestants according to athlete performance level, sex, and discipline. Individual season bests for world-ranked top 100 athletes from 2002 to 2016 (14,937 athletes and 57,049 individual results) were downloaded from the International Association of Athletics Federations’ website. Individual performance trends were generated by fitting a quadratic curve separately to each athlete’s performance and age data using a linear modeling procedure. Mean peak age was typically 25–27 y, but somewhat higher for marathon and male throwers (∼28–29 y). Women reached greater peak age than men in the hurdles and middle- and long-distance running events (mean difference, ±90% CL: 0.6, ±0.3 to 1.9, ±0.3 y: small to moderate). Male throwers had greater peak age than corresponding women (1.3, ±0.3 y: small). Throwers displayed the greatest performance improvements over the 5 y prior to peak age (mean [SD]: 7.0% [2.9%]), clearly ahead of jumpers, long-distance runners, hurdlers, middle-distance runners, and sprinters (3.4, ±0.2% to 5.2, ±0.2%; moderate to large). Similarly, top 10 athletes showed greater improvements than top 11–100 athletes in all events (1.0, ±0.9% to 1.8, ±1.1%; small) except throws. Women improved more than men in all events (0.4, ±0.2% to 2.9, ±0.4%) except sprints. This study provides novel insight on performance development in athletic contestants that are useful for practitioners when setting goals and evaluating strategies for achieving success.
The Association Between Perceived Athletic Competence and Physical Activity: Implications for Low-Income Schoolchildren
Authors: Amin Sarah A. , Duquesnay Paula J. , Wright Catherine M. , Chui Kenneth , Economos Christina D. , Sacheck Jennifer M.
Published: March 2018

Purpose: Socioeconomic status (SES) may impact children’s physical activity (PA) behaviors and confidence to participate in PA. We examined how SES modifies the relationship between children’s perceived athletic competence (PAC) and moderate to vigorous PA (MVPA). Methods: Children (N = 1157; 45% male; grades 3–4) were recruited for the Fueling Learning through Exercise study. Free/reduced price lunch eligibility was used as an indicator of SES. Seven-day accelerometry (ActiGraph GT3X+) was used to measure daily MVPA, out-of-school MVPA (O-MVPA), and school-time MVPA. PAC was assessed using the Harter’s Self-Perception Profile for Children (6 items, scored 1–4; median split: high and low PAC). Results: MVPA and PAC differed between low-SES [n = 556; 41.6 (17.1) min/d; high PAC = 45%] and middle-SES children [n = 412; 49.6 (22.7) min/d; high PAC = 62%]. There was an interaction between SES and PAC for MVPA (P < .001) and O-MVPA (P < .001), but not for school-time MVPA (P > .05). Middle-SES children with high PAC were more likely to engage in MVPA (β = 6.6 min/d; 95% confidence interval, 3.9 to 9.3; P < .001) and O-MVPA (β = 4.8 min/d; 95% confidence interval, 2.8 to 6.8; P < .001), associations that did not exist for low-SES children (P > .05). Conclusions: PAC was positively associated with daily MVPA and O-MVPA, but not among low-SES children. Research is needed to elucidate the factors that shape the relationship between PAC and MVPA.
Age-Predicted Maximal Heart Rate Equations Are Inaccurate for Use in Youth Male Soccer Players
Authors: Cicone Zackary S. , Sinelnikov Oleg A. , Esco Michael R.
Published: March 2018

Purpose: The purpose of this study was to compare the differences between measured (MHRobt) and predicted (MHRpred) maximal heart rate (MHR) in youth athletes. Methods: In total, 30 male soccer players [14.6 (0.6) y] volunteered to participate in this study. MHRobt was determined via maximal-effort graded exercise test. Age-predicted MHR (MHRpred) was calculated for each participant using equations by Fox, Tanaka, Shargal, and Nikolaidis. Mean differences were compared using Friedman’s 2-way analysis of variance and post hoc pairwise comparisons. Agreement between MHRobt and MHRpred values was calculated using the Bland–Altman method. Results: There were no significant differences between MHRobt and MHRpred from the Fox (P = .777) and Nikolaidis (P = .037) equations. The Tanaka and Shargal equations significantly underestimated MHRobt (P < .001). All 4 equations produced 95% limits of agreement of ±15.0 beats per minute around the constant error. Conclusions: The results show that the Fox and Nikolaidis equations produced the smallest mean difference in predicting MHRobt. However, the wide limits of agreement suggests that none of the equations adequately account for individual variability in MHRobt. Practitioners should avoid applying these equations in youth athletes and utilize a lab or field testing protocol to obtain MHR.
Environmental dynamics during the onset of the Middle Stone Age in eastern Africa
Authors: Potts Richard , Behrensmeyer Anna K. , Faith J. Tyler , Tryon Christian A. , Brooks Alison S. , Yellen John E. , Deino Alan L. , Kinyanjui Rahab , Clark Jennifer B. , Haradon Catherine M. , Levin Naomi E. , Meijer Hanneke J. M. , Veatch Elizabeth G. , Owen R. Bernhart , Renaut Robin W.
Published: March 2018

The Middle Stone Age in Africa

The Olorgesailie basin in the southern Kenya rift valley contains sediments dating back to 1.2 million years ago, preserving a long archaeological record of human activity and environmental conditions. Three papers present the oldest East African evidence of the Middle Stone Age (MSA) and elucidate the system of technology and behavior associated with the origin of
Homo sapiens
. Potts
et al.
present evidence for the demise of Acheulean technology that preceded the MSA and describe variations in late Acheulean hominin behavior that anticipate MSA characteristics. The transition to the MSA was accompanied by turnover of large mammals and large-scale landscape change. Brooks
et al.
establish that ∼320,000 to 305,000 years ago, the populations in eastern Africa underwent a technological shift upon procurement of distantly sourced obsidian for toolmaking, indicating the early development of social exchange. Deino
et al.
provide the chronological underpinning for these discoveries.

Science
, this issue p.
86
, p.
90
, p.
95
Factoring stream turbulence into global assessments of nitrogen pollution
Authors: Grant Stanley B. , Azizian Morvarid , Cook Perran , Boano Fulvio , Rippy Megan A.
Published: March 2018

Stream physics set the limits

A combination of physical transport processes and biologically mediated reactions in streams and their sediments removes dissolved inorganic nitrogen (DIN) from the water. Although stream chemistry and biology have been considered the dominant controls on how quickly DIN is removed, Grant
et al.
show that physics is what sets the limits on removal rates of nitrate (a component of DIN). Residence time in the hyporheic zone (the region below the sediment surface where groundwater and surface water mix) determines the maximum rate at which nitrate can be removed from stream water. Nevertheless, at local scales, chemistry and biology modify how closely to that maximum rate removal occurs.

Science
, this issue p.
1266
Societal inequalities amplify gender gaps in math
Authors: Breda Thomas , Jouini Elyès , Napp Clotilde
Published: March 2018

Egalitarian countries cultivate high-performing girls
Beyond PARP—POLθ as an anticancer target
Authors: Higgins Geoff S. , Boulton Simon J.
Published: March 2018

Targeting cancers dependent on DNA polymerase θ has considerable clinical potential
Genetic Relationships among Multidrug-Resistant Salmonella enterica Serovar Typhimurium Strains from Humans and Animals
Authors: Hong Yu-Ping , Wang You-Wun , Huang I-Hsiu , Liao Yu-Chieh , Kuo Hung-Chih , Liu Yen-Yi , Tu Yueh-Hua , Chen Bo-Han , Liao Ying-Shu , Chiou Chien-Shun
Published: March 2018

We identified 20 to 22 resistance genes, carried in four incompatibility groups of plasmids, in each of five genetically closely related
Salmonella enterica
serovar Typhimurium strains recovered from humans, pigs, and chickens. The genes conferred resistance to aminoglycosides, chloramphenicol, sulfonamides, trimethoprim, tetracycline, fluoroquinolones, extended-spectrum cephalosporins and cefoxitin, and azithromycin. This study demonstrates the transmission of multidrug-resistant
Salmonella
strains among humans and food animals and may be the first identification of
mphA
in azithromycin-resistant
Salmonella
strains in Taiwan.
Design of a Broad-Range Bacteriophage Cocktail That Reduces Pseudomonas aeruginosa Biofilms and Treats Acute Infections in Two Animal Models
Authors: Forti Francesca , Roach Dwayne R. , Cafora Marco , Pasini Maria E. , Horner David S. , Fiscarelli Ersilia V. , Rossitto Martina , Cariani Lisa , Briani Federica , Debarbieux Laurent , Ghisotti Daniela
Published: March 2018

The alarming diffusion of multidrug-resistant (MDR) bacterial strains requires investigations on nonantibiotic therapies. Among such therapies, the use of bacteriophages (phages) as antimicrobial agents, namely, phage therapy, is a promising treatment strategy supported by the findings of recent successful compassionate treatments in Europe and the United States. In this work, we combined host range and genomic information to design a 6-phage cocktail killing several clinical strains ofPseudomonas aeruginosa, including those collected from Italian cystic fibrosis (CF) patients, and analyzed the cocktail performance. We demonstrated that the cocktail composed of four novel phages (PYO2, DEV, E215 and E217) and two previously characterized phages (PAK_P1 and PAK_P4) was able to lyseP. aeruginosaboth in planktonic liquid cultures and in biofilms. In addition, we showed that the phage cocktail could cure acute respiratory infection in mice and treat bacteremia in wax moth (Galleria mellonella) larvae. Furthermore, administration of the cocktail to larvae prior to bacterial infection provided prophylaxis. In this regard, the efficiency of the phage cocktail was found to be unaffected by the MDR or mucoid phenotype of the pseudomonal strain. The cocktail was found to be superior to the individual phages in destroying biofilms and providing a faster treatment in mice. We also found theGallerialarva model to be cost-effective for testing the susceptibility of clinical strains to phages, suggesting that it could be implemented in the frame of developing personalized phage therapies.
Positive Regulation of Hepatitis E Virus Replication by MicroRNA-122
Authors: Haldipur Bangari , Bhukya Prudhvi Lal , Arankalle Vidya , Lole Kavita
Published: March 2018

The molecular mechanisms of liver pathology and clinical disease in hepatitis E virus (HEV) infection remain unclear. MicroRNAs (miRNAs) are known to modulate viral pathogenesis either by directly altering viral gene expression or by enhancing cellular antiviral responses. Given the importance of microRNA-122 (miR-122) in liver pathobiology, we investigated possible role of miR-122 in HEV infection.
In silico
predictions using HEV genotype 1 (HEV-1), HEV-2, HEV-3, and HEV-4 sequences showed that the majority of genomes (203/222) harbor at least one miR-122/microRNA-122-3p (miR-122*) target site. Interestingly, HEV-1 genomes showed a highly (97%) conserved miR-122 target site in the RNA-dependent RNA polymerase (RdRp) region (RdRp
c
). We analyzed the significance of miR-122 target sites in HEV-1/HEV-3 (HEV-1/3) genomes by using a replicon-based cell culture system. HEV infection did not change the basal levels of miR-122 in hepatoma cells. However, transfection of these cells with miR-122 mimics enhanced HEV-1/3 replication and depletion of miR-122 with inhibitors led to suppression of HEV-1/3 replication. Mutant HEV-1 replicons with an altered target RdRp
c
sequence (CACTCC) showed a drastic decrease in virus replication, whereas introduction of alternative miR-122 target sites in mutant replicons rescued viral replication. There was enrichment of HEV-1 RNA and miR-122 molecules in RNA-induced silencing complexes in HEV-infected cells. Furthermore, pulldown of miR-122 molecules from HEV-infected cells resulted in pulldown of HEV genomic RNA along with miR-122 molecules. These observations indicate that miR-122 facilitates HEV-1 replication, probably via direct interaction with a target site in the viral genome. The positive role of miR-122 in viral replication presents novel opportunities for antiviral therapy and management of hepatitis E.

IMPORTANCE
Hepatitis E is a problem in both developing and developed countries. HEV infection in most patients follows a self-limited course; however, 20% to 30% mortality is seen in infected pregnant women. HEV superinfections in patients with chronic hepatitis B or hepatitis C virus infections are associated with adverse clinical outcomes, and both conditions warrant therapy. Chronic HEV infections in immunocompromised transplant recipients are known to rapidly progress into cirrhosis. Currently, off-label use of ribavirin (RBV) and polyethylene glycol-interferon (PEG-IFN) as antiviral therapy has shown promising results in both acute and chronic hepatitis E patients; however, the teratogenicity of RBV limits its use during pregnancy, while alpha IFN (IFN-α) increases the risk of transplant rejections. Experimental data determined with genotype 1 virus in the current study show that miR-122 facilitates HEV replication. These observations present novel opportunities for antiviral therapy and management of hepatitis E.
Which observed behaviours may reassure physicians that a child is not septic? An international Delphi study
Authors: Snelson Edward , Ramlakhan Shammi
Published: March 2018

Objective

In an attempt to improve the diagnosis of sepsis in children, diagnostic aids have concentrated on clinical features that suggest that sepsis is present. Clinicians need to be able to clinically rule out sepsis as well as rule it in. Little is known about which features are consistent with wellness and/or absence of sepsis. Guidelines are therefore likely to improve sensitivity without preserving specificity. We aimed to gather expert opinion on which (if any) features would make clinicians consider a child to be unlikely to have sepsis.

Design

We undertook a modified two-round international Delphi study, where clinicians were asked for features they believed were indicators of wellness in an ill child.

Participants

One hundred and ninety-five clinicians (predominantly physicians) who routinely assessed unwell children and had been doing so for most of their careers.

Results

Over 90% of respondents rated age-appropriate verbalisation, playing, smiling and activity as reassuring that a child was unlikely to have sepsis. Eating, spontaneous interaction and normal movement were also agreed to be reassuring by over 70% of participants. Consolability and showing fear of the clinician were not felt to be adequately reassuring. There was wide range of opinion on how reassuring the use of an electronic device was thought to be.

Conclusions

This study confirms that physicians are reassured by specific behaviours in ill children, and provides a framework which may be used to help guide the assessment of the unwell child. Validation of individual features could lead to improved specificity of diagnostic aids for diagnosing sepsis.
Economic burden of HIV and TB/HIV coinfection in a middle-income country: a costing analysis alongside a pragmatic clinical trial in Brazil
Authors: Teixeira de Siqueira-Filha Noemia , Militao de Albuquerque Maria de Fatima , Cunha Rodrigues Laura , Legood Rosa , Costa Santos Andreia
Published: March 2018

Objective

The objective of this study was to measure the costs of people living with HIV (PLHIV) as well as active tuberculosis (TB/HIV), latent tuberculosis infection (LTBI/HIV) or without TB (HIV/AIDS).

Methods

We analysed the costs through the entire pathway of care during the prediagnosis and treatment periods from the Brazilian public health system perspective. We applied a combination of bottom-up and top-down approaches to capture and estimate direct medical and non-medical costs. We measured the mean cost per patient per type of care (inpatient, outpatient and emergency care) and disease category (HIV/AIDS, HIV/AIDS death, TB/HIV, TB/HIV death and LTBI/HIV).

Results

Between March 2014 and March 2016 we recruited 239 PLHIV. During the follow-up 26 patients were diagnosed and treated for TB and 5 received chemoprophylaxis for LTBI. During the prediagnosis and treatment period, the mean total costs for HIV or AIDS and AIDS death categories were US$1558 and US$2828, respectively. The mean total costs for TB/HIV and TB/HIV death categories were US$5289.0 and US$8281, respectively. The mean total cost for the LTBI/HIV category was US$882.

Conclusions

Patients with TB/HIV impose a higher economic burden on the health system than HIV/AIDS and LTBI/HIV. Patients with LTBI/HIV were the lowest cost group among all disease categories, indicating that preventive TB treatment can avoid the further costs treating active TB.

Trial registration number

RBR-22t943, Results.
Recovered case of sheep‐associated malignant catarrhal fever in a gravid cow
Authors: Stanitznig Anna , Wittek Thomas
Published: March 2018

A four‐year‐old Brown Swiss cow was referred to the University Clinic for Ruminants in Vienna. At the first clinical examination the cow showed the following clinical signs: body condition score 2 out of 5, respiratory rate of 38 per minute, body temperature of 38.1°C, moderate hyperaemia of the conjunctival mucous membranes with severe serous ocular discharge, injection of the scleral vessels and bilateral opacity of the cornea were present. The nasal mucous membranes were pink and a moderate amount of mucopurulent nasal discharge was present. Harsh lung sounds were audible at auscultation and all teats presented with multiple erosions. Definitive diagnosis was the eye form of malignant catarrhal fever with additional pathological changes at the teats. The cow was treated intensively with antibiotics, NSAID, intravenous infusion (sodium chloride and glucose) and rumen fluid, and was discharged from the clinic seven days after admission. The offspring was clinically healthy.
l-Arginine supplementation does not improve muscle function during recovery from resistance exercise
Authors: Andrade Walquiria Batista , Jacinto Jeferson Lucas , da Silva Douglas Kratki , Roveratti Mirela Casonato , Estoche José Maria , Oliveira Douglas Benedito , Balvedi Mario Carlos Welin , da Silva Rubens Alexandre , Aguiar Andreo Fernando
Published: March 2018

The purpose of this study was to investigate the effects of l-arginine supplementation on muscle recovery after a single session of high-intensity resistance exercise (RE). Twenty healthy young adult participants (22.8 ± 3.4 years old) were assigned to 1 of 2 groups (N = 10 per group): a placebo-supplement group or an l-arginine-supplement group. The groups completed a session of high-intensity RE (0 h) and 3 subsequent fatigue test sessions (at 24, 48, and 72 h postexercise) to assess the time course of muscle recovery. During the test sessions, we assessed the following dependent variables: number of maximum repetitions, electromyographic signal (i.e., root mean square (RMS) and median frequency (MF) slope), muscle soreness, perceived exertion, blood levels of creatine kinase (CK) and lactate, and testosterone:cortisol ratio. Number of maximum repetitions increased at 48 and 72 h postexercise in both groups (time, P < 0.05). CK levels and muscle soreness increased at 24 h postexercise and then progressively returned to baseline at 72 h post exercise in both groups (time, P < 0.05). Lactate levels increased immediately postexercise but were reduced at 24 h postexercise in both groups (time, P < 0.05). Testosterone:cortisol ratio, RMS, and MF slope remained unchanged during the recovery period in both groups (time, P > 0.05). No significant (P > 0.05) group × time interaction was found for all dependent variables during the recovery period. In conclusion, our data indicate that l-arginine supplementation does not improve muscle recovery following a high-intensity RE session in young adults.
Searching for the doubly charged scalars in the Georgi–Machacek model via γγ collisions at the ILC
Authors: Cao Jun , Li Yu-Qi , Liu Yao-Bei
Published: March 2018

The Georgi–Machacek (GM) model predicts the existence of the doubly-charged scalars [Formula: see text], which can be seen the typical particles in this model and their diboson decay channels are one of the most promising ways to discover such new doubly-charged scalars. Based on the constraints of the latest combined ATLAS and CMS Higgs boson diphoton signal strength data at [Formula: see text] confidence level, we focus on the study of the triple scalar production in [Formula: see text] collisions at the future International Linear collider (ILC): [Formula: see text], where the production cross-sections are very sensitive to the triple scalar coupling parameter [Formula: see text]. Considering the typical same-sign diboson decay modes for the doubly-charged scalars, the possible final signals might be detected via this process at the future ILC experiments.
A note on Gamma Wick products
Authors: Catrina Florin , Stan Aurel I.
Published: March 2018

An integral representation of the Wick product for Gamma distributed random variables, with mean greater than [Formula: see text], is presented first. We use this integral representation to prove a Hölder inequality for norms of Gamma Wick products.
Cell-Based Smoothed Finite Element Method for the Intensity Factors of Piezoelectric Bimaterials with Interfacial Crack
Authors: Zhou Liming , Li Ming , Zhao Hongwei , Tian Weijun
Published: March 2018

To improve the precision in resolving interfacial crack intensity factor of piezoelectric bimaterials in practical engineering, we proposed a cell-based smoothed finite element method (CS-FEM) that simulated the displacement field and electric field near the crack tips of piezoelectric bimaterials. The displacement field and electric field at the nodes behind crack tips were extracted and substituted into the extrapolation method of interfacial cracks of out-of-phase anisotropic piezoelectric bimaterials, aiming to solve the interfacial crack intensity factor of transversally isotropic piezoelectric bimaterials. With double-piezoelectric flat-plates containing center cracks as example, we investigated the intensity factors of different materials, loads, cell number and encryption modes. The results were compared with FEM and analytic solutions. Results of numerical cases showed that CS-FEM was computationally simple, precise and reliable and thus was attractive to engineers.
EXPLAINING CROSS-NATIONAL VARIATIONS IN THE PREVALENCE OF INFORMAL SECTOR ENTREPRENEURSHIP: LESSONS FROM A SURVEY OF 142 COUNTRIES
Authors: WILLIAMS COLIN C. , KEDIR ABBI
Published: March 2018

The aim of this paper is to evaluate four competing theoretical perspectives that explain cross-national variations in the level of informal sector entrepreneurship. Scholarship has until now argued that informal entrepreneurship is a result of either: economic under-development and a lack of modernization of governance (modernization theory); high taxes and state over-interference (neo-liberal theory); inadequate state intervention to protect workers from poverty (political economy theory) or the asymmetry between the laws and regulations of formal institutions and the unwritten socially shared rules of informal institutions (institutional theory). Reporting the World Bank Enterprise Survey (WBES) on the varying prevalence of informal entrepreneurship across 142 countries, the finding is that neo-liberal theory is refuted but the tenets of the modernization, political economy and institutional theories are confirmed. Informal entrepreneurship is found to be significantly higher when there is economic under-development, a lack of modernization of governance, inadequate state intervention to protect workers from poverty and greater asymmetry between the formal and informal institutions. The paper concludes by discussing the theoretical and policy implications of these findings.
Prediction of Vibration Behavior of Micro-Circular Disks at Low Reynolds Number Regime
Authors: El Baroudi Adil , Razafimahery Fulgence
Published: March 2018

In the current study, a theoretical method is developed to predict the vibrational behavior of micro-circular disks filled with viscous fluids and numerical results are presented to validate the model. Vibrations with two outer boundary conditions, rigid and deformable vessel, are studied. The coupled governing equations of both rigid and deformable vessel vibration are solved by the analytical procedure, taking fluid–structure interaction into account. The fluid gap effect on the coupled eigenfrequencies is also considered. The frequency spectrum plots of the first several eigenfrequencies are presented in a wide range of fluid gap and elasticity ratio. The correctness of results is demonstrated using a commercial finite element software. It is shown that the obtained results through the proposed method reveal very good agreement with the numerical solution.