bluuebunny/crossref_metadata_2025 huggingface dataset:
Has Tranexamic Acid in Total Knee Arthroplasty Made Tourniquet Use Obsolete?
Authors: Brusalis Christopher M. , Bostrom Mathias P. G. , Richardson Shawn S.
Published: August 2018

The application of tranexamic acid (TXA) in total joint arthroplasty has dramatically improved peri-operative blood management. In light of these benefits, a study by Huang et al., “Intravenous and Topical Tranexamic Acid Alone Are Superior to Tourniquet Use for Primary Total Knee Arthroplasty,” evaluates the need for continued use of the intra-operative tourniquet, which remains a routine practice with documented benefits and adverse effects. This review evaluates the study's design and critically interprets its findings for clinical practice. Through a prospective, randomized trial, Huang et al. demonstrated that among selected patients undergoing primary total knee arthroplasty, the use of a tourniquet results in no reduction in blood loss beyond that provided by TXA alone. Moreover, the use of TXA without a tourniquet led to improved early clinical outcomes such as reduced post-operative swelling, improved knee range of motion at discharge, and enhanced patient satisfaction. As medicine is practiced in an increasingly value-driven environment, this study provides a useful method for evaluating the utility of commonly used interventions. Its findings highlight the need for future investigations into the optimal administration of TXA in total knee arthroplasty.
Outcome of Patients With Inherited Neurotransmitter Disorders
Authors: Cordeiro Dawn , Bullivant Garrett , Cohn Ronald D. , Raiman Julian , Mercimek-Andrews Saadet
Published: August 2018

We report the outcome of 12 patients with inherited neurotransmitter disorders of monoamine, tetrahydrobiopterin and γ amino butyric acid metabolisms from a single Inherited Neurotransmitter Disorder Clinic including tyrosine hydroxylase (n=2), aromatic l-amino acid decarboxylase (n=1), 6-pyruvoyltetrahydropterin synthase, dihydropteridine reductase and succinic semialdehyde dehydrogenase deficiencies. Six patients (with 6-pyruvoyltetrahydropterin synthase, dihydropteridine reductase and tyrosine hydroxylase deficiencies) had normal neurodevelopmental outcome on treatment. Tetrahydrobiopterin loading test in newborns with positive newborn screening for phenylketonuria will identify patients with 6-pyruvoyltetrahydropterin synthase and dihydropteridine reductase deficiencies resulting in abnormal neurotransmitter synthesis in the central nervous system in the neonatal period to initiate disease-specific treatment to improve neurodevelopmental outcome.
Vernacular imaginaries of European border security among citizens: From walls to information management
Authors: Löfflmann Georg , Vaughan-Williams Nick
Published: August 2018

Our primary aim in this article is to explore vernacular constructions of Europe’s so-called ‘migration crisis’ from the grounded everyday perspectives of EU citizens. We do so as a critical counterpoint to dominant elite scripts of the crisis, which are often reliant upon securitised representations of public opinion as being overwhelmingly hostile to migrants and refugees and straightforwardly in favour of tougher deterrent border security. In addition to broadening the range of issues analysed in vernacular security studies, the article seeks to make three principal contributions. Theoretically, we argue for an approach to the study of citizens’ views and experiences of migration and border security that is sensitive to the performative effects of research methods and the circular logic between securitising modes of knowledge production and policy justification. Methodologically, we outline and apply an alternative approach in response to these dynamics, drawing on the potential of critical focus groups and a desecuritising ethos. Empirically, we identify a vernacular theory of ‘the border’ asinformation management, and a significantinformation gapprevalent among participants with otherwise opposing views towards migration. These findings challenge bifurcated understandings of public opinion towards migration into Europe and point to the existence of vernacular border security imaginaries beyondeither‘closed’or‘open’ borders.
A STRUCTURED INVERSE SPECTRUM PROBLEM FOR INFINITE GRAPHS AND
UNBOUNDED OPERATORS
Authors: KHANMOHAMMADI EHSSAN
Published: August 2018

Let $G$ be an infinite graph on countably many vertices and let $\unicode[STIX]{x1D6EC}$ be a closed, infinite set of real numbers. We establish
the existence of an unbounded self-adjoint operator whose graph is $G$ and whose spectrum is $\unicode[STIX]{x1D6EC}$.
ON THE ABSENCE OF ZEROS IN INFINITE ARITHMETIC PROGRESSION FOR
CERTAIN ZETA FUNCTIONS
Authors: SRICHAN TEERAPAT
Published: August 2018

Putnam [‘On the non-periodicity of the zeros of the Riemann zeta-function’,
Amer. J. Math.76 (1954), 97–99] proved that
the sequence of consecutive positive zeros of $\unicode[STIX]{x1D701}(\frac{1}{2}+it)$ does not contain any infinite arithmetic progression. We
extend this result to a certain class of zeta functions.
Hypophosphataemia in infants with CHD treated with amino acid infant formula
Authors: Marino Luise V. , Venkatesh Prathana , Ho Andy , Beattie R. Mark , Bharucha Tara
Published: August 2018

Objective

Growth among infants with CHD is poor, and is multifactorial with multiple contributing factors. Unexplained hypophosphataemia has been reported among infants and children with complex medical needs consuming amino acid infant formula as the sole source of nutrition. The aim of this audit was therefore to review the incidence of hypophosphataemia among infants with CHD.

Methods

The use of an electronic patient record search for “amino acid infant formula”, “CHD”, and “cardiac” yielded 136 infants <12 months of age. Preterm infants (n=24), children with chromosomal abnormalities (n=4), those >1 year of age (n=11) and infants with a structurally normal heart (n=31) were excluded from the study. The remaining 66 infants with CHD were given amino acid infant formula.

Measurements and main results

In all, 1059 serum phosphate measures were available. After the introduction of amino acid infant formula, significantly more infants with CHD had episodes of hypophosphataemia: 15% (n=10/66) before treatment versus 29% (n=19/66) after treatment (p=0.049). Mean serum phosphate levels were significantly lower in infants with CHD following consumption of amino acid infant formula (2.0±0.5 versus 1.5±0.5 mmol/L following treatment (p<0.0001)). Infants with CHD and hypophosphataemia, associated with amino acid infant formula, use demonstrated significantly lower weight gain compared with those with normal phosphate levels (weight-for-age z scores −2.1±1.4 versus –0.9±1.5; p<0.0001).

Conclusion

After the introduction of an amino acid formula, weight gain was significantly lower among those infants with low phosphate levels. There was a significantly higher prevalence of hypophosphataemia among infants with CHD after the introduction of amino acid infant formula. Lower phosphate levels were associated with lower weight-for-age z scores. Infants with CHD are susceptible to poor weight gain; it is therefore, crucial the nutritional status of infants prescribed amino acid infant formula is more closely monitored to ensure adequate growth.
Nutritional quality of meals offered to children (kids’ meals) at chain restaurants in Japan
Authors: Uechi Ken
Published: August 2018

Objective

To evaluate the nutritional quality, particularly the fat and salt contents, of meals offered to children (kids’ meals) at chain restaurants in Japan.

Design

A web-based content analysis was conducted to evaluate the type of restaurant, type of meal, incentives, health claims and nutrition data of kids’ meals. The nutritional appropriateness of kids’ meals was assessed with the Standard for the School Lunch Program, which regulates energy (≤2218 kJ), protein (20–30 g), fat (≤30 % of energy (E%)) and salt (<2 g) contents of the school lunch in Japan. Linear mixed models were employed for evaluating the relationship between the characteristics of kids’ meals and their fat (E%) or salt (g) content.

Setting

Restaurant websites providing nutritional data of kids’ meals in Japan.

Subjects

A total of 438 kids’ meals offered by forty-two chain restaurant brands from across twenty food-service companies.

Results

Overall, 58·9, 40·6 and 34·5 % of the kids’ meals were determined to be appropriate regarding their energy (≤2218 kJ), fat (≤30 E%) and salt content (<2 g). In addition, 15·5 % of kids’ meals met the multiple standards of energy, fat and salt contents. ‘Japanese-style’ (restaurant-level characteristic) was associated with a decrease in the fat E% of kids’ meals (β=−6·2; 95 % CI −11·0, −1·4) and an increase in the salt content (β=0·7; 95 % CI 0·06, 1·3).

Conclusions

The characteristics of the restaurant-served kids’ meals in Japan were high fat E% and high salt content from different cultural contexts of the Western and the Japanese diet.
Levels and correlates of nutritional status of women of childbearing age in rural Bangladesh
Authors: Khanam Rasheda , Lee Anne Shee CC , Ram Malathi , Quaiyum MA , Begum Nazma , Choudhury Allysha , Christian Parul , Mullany Luke C , Baqui Abdullah H ,   for the MIST Study Team of the Projahnmo Study Group in Bangladesh
Published: August 2018

Objective

The present study examined the prevalence of and risk factors for malnutrition in a population-based cohort of women of childbearing age in rural Bangladesh.

Design

A cross-sectional study that collected pre-pregnancy weight, height, and data on selected risk factors for nutritional status of women.

Setting

The study was conducted in Sylhet District of Bangladesh.

Subjects

Study subjects included 13 230 non-pregnant women of childbearing age. Women were classified into underweight (<18·5 kg/m2), normal (18·5–24·9 kg/m2) and overweight/obese (≥25·0 kg/m2) using BMI; and into moderate to severe stunting (<150 cm), mild stunting (150–<155 cm) and normal (≥155 cm) using height. Two multinomial logistic regression models were fitted for BMI: model 1 examined individual and household factors associated with BMI, and model 2 additionally examined the association of community variables. The same analysis was conducted for height.

Results

Prevalence of underweight, overweight/obesity and moderate to severe stunting was 37·0, 7·2 and 48·6 %, respectively. Women’s education and household wealth were inversely related to both underweight status and stunting. Underweight rate was significantly lower in the post-harvest season. Women with any education and who belonged to households with higher wealth were more likely to be overweight/obese.

Conclusions

The study documented high underweight and stunting, and moderate overweight/obesity rates among rural Bangladeshi women; and recommends design and implementation of a multidimensional intervention programme based on individual-, household- and community-level risk factors that can address underweight, stunting and overweight/obesity to improve the nutritional status of women of childbearing age in Bangladesh.
ON VALUES TAKEN BY THE LARGEST PRIME FACTOR OF SHIFTED PRIMES
Authors: WU JIE
Published: August 2018

Denote by$\mathbb{P}$the set of all prime numbers and by$P(n)$the largest prime factor of positive integer$n\geq 1$with the convention$P(1)=1$. In this paper, we prove that, for each$\unicode[STIX]{x1D702}\in (\frac{32}{17},2.1426\cdots \,)$, there is a constant$c(\unicode[STIX]{x1D702})>1$such that, for every fixed nonzero integer$a\in \mathbb{Z}^{\ast }$, the set$$\begin{eqnarray}\{p\in \mathbb{P}:p=P(q-a)\text{ for some prime }q\text{ with }p^{\unicode[STIX]{x1D702}}<q\leq c(\unicode[STIX]{x1D702})p^{\unicode[STIX]{x1D702}}\}\end{eqnarray}$$has relative asymptotic density one in$\mathbb{P}$. This improves a similar result due to Banks and Shparlinski [‘On values taken by the largest prime factor of shifted primes’,J. Aust. Math. Soc.82(2015), 133–147], Theorem 1.1, which requires$\unicode[STIX]{x1D702}\in (\frac{32}{17},2.0606\cdots \,)$in place of$\unicode[STIX]{x1D702}\in (\frac{32}{17},2.1426\cdots \,)$.
A profile of humanity: the cultural signature of Earth's inhabitants beyond the atmosphere
Authors: Quast Paul E.
Published: August 2018

The eclectic range of artefacts and ‘messages’ we dispatch into the vast expanse of space may become one of the most enduring remnants of our present civilization, but how does his protracted legacy adequately document the plurality of societal values and common, cultural heritage on our heterogeneous world? For decades now, this rendition of the egalitarian principle has been explored by the Search for Extra-Terrestrial Intelligence community in order to draft theoretical responses to ‘who speaks for Earth?’ for hypothetical extra-terrestrial communication strategies. However, besides the moral, ethical and democratic advancements made by this particular enterprise, there remains little practical exemplars of implementing this garnered knowledge into other experimental elements that could function as mutual emissaries of Earth; physical artefacts that could provide accessible details about our present world for future archaeological observations by our space-faring progeny, potential visiting extrasolar denizens or even for posterity. While some initiatives have been founded to investigate this enduring dilemma of humanity over the last half-century, there are very few comparative studies in regards to how these objects, time capsules and transmission events collectively disseminate content about the aggregate of our species and the Earth system it inhabits. This catalogue, assembled for extended study as part of theBeyond the Earth foundation, is intended as an initial, dialogic step towards evaluating such a ‘profile of humanity’. This investigation will endeavour to collate all cultural resources that can presently be garnered from spacecraft (non-mission orientated, cultural material that conveys an impression of Earth) and non-terrestrial transmissions (electromagnetic signals that are intentionally aimed off-world to embody humanities’ evolving, philosophical identity) in the expanse beyond our planetary borders in order to cross-analyse how we presently illustrate the diversity of our planet before, subsequently, deducing how we could appropriately depict our collective human civilization [and biosphere] within deep space and cosmic time.
Depressive, anxiety, and distress symptoms among cancer patients who endorse appearance problems
Authors: Chopra Deepti , De La Garza Richard
Published: August 2018

Objective

Body image is a vital and complex issue in cancer patients, but not well recognized. In the ambulatory psychiatric-oncology clinic, we assessed what portion of cancer patients endorsed appearance problems and if they differed in terms of depression, anxiety, or distress scores when compared with those who did not endorse appearance problems.

Method

All adult patients with active cancer diagnosis seen in the outpatient psychiatry oncology clinic (June 2014–January 2016) who provided informed consent were included (N = 1,939) in the cross-sectional study design. “Appearance problems” were assessed as a categorical, binomial variable (yes/no) using the National Comprehensive Cancer Network Distress Thermometer checklist. Other assessments included the Patient Health Questionnaire-9, Patient Health Questionnaire-2, Generalized Anxiety Disorder-7, Distress Thermometer, and Edmonton Symptom Assessment Scale.

Result

The overall prevalence rate of individuals who endorsed appearance problems was approximately 36%; they were more likely to be younger, female, Black or Hispanic, and not in a committed relationship (all results for demographic variables were statistically significant; all p < .001). Importantly, those patients who endorsed appearance problems exhibited higher scores for depression (p < .0001), anxiety (p < .0001), and distress (p < .0001), and these differences were of medium effect size (Cohen's d = 0.5−0.6).

Significance of results

The current results underscore the need to identify patients with body image problems early given that they are likely to exhibit higher magnitude of anxiety, depression and distress symptoms while undergoing cancer care. The results highlight the importance of body image issues and the need to evaluate them in cancer patients.
Comparing the Effectiveness of Brief Versus In-Depth Gatekeeper Training on Behavioral Outcomes for Trainees
Authors: Condron Susanne , Godoy Garraza Lucas , Kuiper Nora , Sukumar Bhuvana , Walrath Christine , McKeon Richard
Published: August 2018

Abstract. Background: A common suicide prevention strategy is training gatekeepers to identify at-risk individuals and refer them to services. Aims: The study aimed to examine whether differences in training outcomes were observed for brief versus in-depth gatekeeper trainings for trainees from varied professional settings while controlling for differences in trainee characteristics and community context. Method: Trainees' identification and referral behavior 3 months after gatekeeper training was compared with a sample of respondents matched on individual- and community-level variables using propensity score-based techniques. The value was estimated, in terms of additional identification and associated costs, of adopting in-depth training. Results: A higher proportion of trainees who participated in in-depth trainings from K-12 and community settings identified at-risk youth, and a higher proportion of in-depth trainees from mental health settings referred youth to services compared with participants of brief trainings from the same setting and with similar characteristics. The effect of training type on outcomes varied by professional role and community context. Limitations: Self-report measures were used to assess outcomes. Similar measures are used in other studies; their validity has not been conclusively established. Conclusion: Findings suggest certain individuals may benefit from in-depth training more than others, which favors targeting this intervention to particular gatekeepers.
Comparing Indicators of Suicidality Among Users in Different Types of Nonprofessional Suicide Message Boards
Authors: Van den Nest Miriam , Till Benedikt , Niederkrotenthaler Thomas
Published: August 2018

Abstract. Background: Little is known about linguistic differences between nonprofessional suicide message boards that differ in regard to their predominant attitude to suicide. Aims: To compare linguistic indicators potentially related to suicidality between anti-suicide, neutral, and pro-suicide message boards, and between the types of posters (primary posters, who initiate the thread, and the respective respondents). Method: In all, 1,200 threads from seven German-language nonprofessional suicide message boards were analyzed using the software Linguistic Inquiry and Word Count (LIWC) with regard to wording related to suicidal fantasies, aggression, and indicators of so-called suicidal constriction. Data were analyzed with ANOVA. Results: There were fewer words related to affective, social, cognitive, and communicative processes in pro-suicide message boards than in other boards. Death-related wording and aggression as well as tentative wording appeared more prevalent in pro-suicide boards. Limitations: Complex language structures cannot be analyzed with LIWC. Conclusion: The results suggest fewer emotion words and wording related to social circumstances among primary posters and respondents in pro-suicide boards as compared with other boards, and a higher use of death- and aggression-related words. These findings might signal a higher degree of suicidality or sheer differences in matters of interest or social desirability. The differences require attention in practice and research.
Triangulation and Coupling of Gigantic Jets Near the Lower Ionosphere Altitudes
Authors: Peng Kang‐Ming , Hsu Rue‐Ron , Chang Wei‐Yu , Su Han‐Tzong , Chen Alfred Bing‐Chih , Chou Jung‐Kuang , Wu Yen‐Jung , Chang Shu‐Chun , Hung Chien‐Lun , Yang I‐Ching , Tsai Sung‐Hui
Published: August 2018

Coordinated TLE (transient luminous event) optical observations in Taiwan have been held since 2011, with an aim to achieve triangulation. Currently, there are four observation stations with baselines varying from 100 to 400 km between them. The system recorded eight gigantic jets (GJs) that were recorded by at least two stations on the night of 20 August 2014. The weather radar data indicate that these GJs occurred around the troposphere overshooting tops of a vigorous cumulonimbus cloud. A leader‐to‐streamer transition was discerned as the appearance of these GJs changed from jet‐like (leader) to fan‐like (streamer) at ~40 km altitude. Most of these GJs terminated at the lower ionosphere boundary (80–90 km), but one GJ topped with a 10 km thick diffuse region extended higher than 100 km. Moreover, three sets of the GJs occurred within 0.5–100 s in the same general region. The residual plasma patches from the preceding GJs appear to cause the subsequent GJs to contain more bead structures and to be brighter. Also, three streamer columns of a subsequent GJ that occurred more than 100 s after the preceding GJ were identified to have rebrightened at 55 to 70 km altitudes. The rebrightened streamers and the bead structure increments in the subsequent GJs suggest that there were GJ‐produced long‐lasting plasma patches in the mesosphere.
Effect of Solution pH and Chloride Concentration on Akaganeite Precipitation: Implications for Akaganeite Formation on Mars
Authors: Peretyazhko T. S. , Ming D. W. , Rampe E. B. , Morris R. V. , Agresti D. G.
Published: August 2018

Akaganeite, a chloride‐bearing Fe(III) (hydr)oxide, has been reported on Mars in Yellowknife Bay in Gale crater by X‐ray diffraction (XRD), in Robert Sharp crater by Compact Reconnaissance Imaging Spectrometer for Mars, and possibly at the Gusev crater and Meridiani Planum by combined Mössbauer and bulk chemistry analyses. Because formation conditions remain unknown, we investigated akaganeite precipitation as a function of solution pH and chloride concentration. Akaganeite was synthesized through hydrolysis of Fe(III) perchlorate in the presence of 0.02, 0.05, and 0.1 M chloride and at initial solution pH of 1.6, 4, 6, and 8 at 90 °C. Mineralogy of the precipitated Fe(III) (hydr)oxides was characterized by XRD, infrared spectroscopy, and Mössbauer spectroscopy. Total chloride and perchlorate contents were determined by ion chromatography. XRD revealed that akaganeite formed alone or in mixtures with ferrihydrite, hematite, and/or goethite at initial pH 1.6 with 0.02, 0.05, and 0.1 M Cl− and at initial pH from 4 to 8 with 0.05 and 0.1 M Cl−. Infrared analysis showed that akaganeite bands at ~2 and ~2.45 μm were sensitive to amount of akaganeite, total chloride content, and presence of other Fe(III) (hydr)oxides. The results indicate that akaganeite in Yellowknife Bay in Gale crater likely formed under acidic to alkaline (1.6 < pH < 8) oxidizing conditions in solutions containing >0.05 M Cl− by the dissolution of basaltic minerals. Akaganeite in Robert Sharp crater may have formed in acidic (pH < 4) solutions with ~0.1 M Cl− through oxidative dissolution of Fe(II) sulfides and/or acidic oxidizing dissolution of basalts.
Lithospheric Controls on the Rifting of the Tanzanian Craton at the Eyasi Basin, Eastern Branch of the East African Rift System
Authors: Fletcher Andrew W. , Abdelsalam Mohamed G. , Emishaw Luelseged , Atekwana Estella A. , Laó‐Dávila Daniel A. , Ismail Ahmed
Published: August 2018

Continental rifts most often nucleate within orogenic belts. However, some studies in the East African rift system have shown that continental rifts can also develop within cratons. This work investigated the ~1.5‐Ma Eyasi basin, which propagates in a WSW direction into the Tanzanian craton. The basin is located where the eastern branch of the East African rift system transitions from a narrow rift (~70 km wide) to the wider (~300 km wide) North Tanzanian Divergence. Unlike the rest of the eastern branch segments, the Eyasi basin does not follow the Mozambique orogenic belt located on the eastern margin of the Tanzanian craton. This work generated lithospheric‐scale sections across the basin using (1) digital elevation model to map surface rift‐related brittle structures; (2) aeromagnetic data to determine the depth to the Precambrian basement; and (3) World Gravity Model 2012 to estimate crustal and lithospheric thickness by applying the two‐dimensional radially averaged power spectral analysis and two‐dimensional forward gravity modeling. These cross sections show that the Eyasi basin nucleates within a previously unidentified suture zone within the Tanzanian craton and that this suture zone is characterized by thinner lithosphere that can be as thin as ~95 km. This zone of thinner lithosphere is offset southeastward from the surface expression of the Eyasi basin and might have facilitated the formation of other basins further south. Furthermore, the lithospheric thickness map indicates that the Tanzanian craton is heterogeneous and possibly composed of multiple smaller cratonic fragments.
Monitoring Stray Natural Gas in Groundwater With Dissolved Nitrogen. An Example From Parker County, Texas
Authors: Larson Toti E. , Nicot Jean‐Philippe , Mickler Patrick , Castro M. Clara , Darvari Roxana , Wen Tao , Hall Chris M.
Published: August 2018

Concern that hydraulic fracturing and natural gas production contaminates groundwater requires techniques to attribute and estimate methane flux. Although dissolved alkane and noble gas chemistry may distinguish thermogenic and microbial methane, low solubility and concentration of methane in atmosphere‐equilibrated groundwater precludes the use of methane to differentiate locations affected by high and low flux of stray methane. We present a method to estimate stray gas infiltration into groundwater using dissolved nitrogen. Due to the high concentration of nitrogen in atmospheric‐recharged groundwater and low concentration in natural gas, dissolved nitrogen in groundwater is much less sensitive to change than dissolved methane and may differentiate groundwater affected high and low flux of stray natural gas. We report alkane and nitrogen chemistry from shallow groundwater wells and eight natural gas production wells in the Barnett Shale footprint to attribute methane and estimate mixing ratios of thermogenic natural gas to groundwater. Most groundwater wells have trace to nondetect concentrations of methane. A cluster of groundwater wells have greater than 10 mg/L dissolved methane concentrations with alkane chemistries similar to natural gas from the Barnett Shale and/or shallower Strawn Group suggesting that localized migration of natural gas occurred. Two‐component mixing models constructed with dissolved nitrogen concentrations and isotope values identify three wells that were likely affected by a large influx of natural gas with gas:water mixing ratios approaching 1:5. Most groundwater wells, even those with greater than 10‐mg/L methane, have dissolved nitrogen chemistry typical of atmosphere‐equilibrated groundwater suggesting natural gas:water mixing ratios smaller than 1:20.
Metal-free alcohol-directed regioselective heteroarylation of remote unactivated C(sp3)–H bonds
Authors: Wu Xinxin , Zhang Hong , Tang Nana , Wu Zhen , Wang Dongping , Ji Meishan , Xu Yan , Wang Min , Zhu Chen
Published: August 2018

Construction of C–C bonds via alkoxy radical-mediated remote C(sp3)–H functionalization is largely unexplored, as it is a formidable challenge to directly generate alkoxy radicals from alcohols due to the high bond dissociation energy (BDE) of O–H bonds. Disclosed herein is a practical and elusive metal-free alcohol-directed heteroarylation of remote unactivated C(sp3)–H bonds. Phenyliodine bis(trifluoroacetate) (PIFA) is used as the only reagent to enable the coupling of alcohols and heteroaryls. Alkoxy radicals are readily generated from free alcohols under the irradiation of visible light, which trigger the regioselective hydrogen-atom transfer (HAT). A wide range of functional groups are compatible with the mild reaction conditions. Two unactivated C–H bonds are cleaved and one new C–C bond is constructed during the reaction. This protocol provides an efficient strategy for the late-stage functionalization of alcohols and heteroaryls.
Structural basis for membrane tethering by a bacterial dynamin-like pair
Authors: Liu Jiwei , Noel Jeffrey K. , Low Harry H.
Published: August 2018

Dynamin-like proteins (DLPs) are large GTPases that restructure membrane. DLPs such as the mitofusins form heterotypic oligomers between isoform pairs that bridge and fuse opposing membranes. In bacteria, heterotypic oligomerisation may also be important for membrane remodelling as most DLP genes are paired within operons. How DLPs tether opposing membranes is unknown. Here we show the crystal structure of a DLP heterotypic pair from the pathogen Campylobacter jejuni. A 2:2 stoichiometric tetramer is observed where heterodimers, conjoined by a random coil linker, assemble back-to-back to form a tripartite DLP chain with extreme flexibility. In vitro, tetramerisation triggers GTPase activity and induces lipid binding. Liposomes are readily tethered and form tubes at high tetramer concentration. Our results provide a direct mechanism for the long-range binding and bridging of opposing membranes by a bacterial DLP pair. They also provide broad mechanistic and structural insights that are relevant to other heterotypic DLP complexes.
Regenerative medicine and war: a front-line focus for UK defence
Authors: Spear Abigail M. , Lawton Graham , Staruch Robert M. T. , Rickard Rory F.
Published: August 2018

The recent prolonged conflicts in Iraq and Afghanistan saw the advancement of deployed trauma care to a point never before seen in war. The rapid translation of lessons from combat casualty care research, facilitated by an appetite for risk, contributed to year-on-year improvements in care of the injured. These paradigms, however, can only ever halt the progression of damage. Regenerative medicine approaches, in contrast, hold a truly disruptive potential to go beyond the cessation of damage from blast or ballistic trauma, to stimulate its reversal, and to do so from a very early point following injury. The internationally distributed and, in parts austere environments in which operational medical care is delivered provide an almost unique challenge to the development and translation of regenerative medicine technologies. In parallel, however, an inherent appetite for risk means that Defence will always be an early adopter. In focusing our operational priorities for regenerative medicine, the authors conducted a review of the current research landscape in the UK and abroad and sought wide clinical opinion. Our priorities are all applicable very far forward in the patient care pathway, and are focused on three broad and currently under-researched areas, namely: (a) blood, as an engineered tissue; (b) the mechanobiology of deep tissue loss and mechanobiological approaches to regeneration, and; (c) modification of the endogenous response. In focusing on these areas, we hope to engender the development of regenerative solutions for improved functional recovery from injuries sustained in conflict.
AS03-adjuvanted H5N1 vaccine promotes antibody diversity and affinity maturation, NAI titers, cross-clade H5N1 neutralization, but not H1N1 cross-subtype neutralization
Authors: Khurana Surender , Coyle Elizabeth M. , Manischewitz Jody , King Lisa R. , Gao Jin , Germain Ronald N. , Schwartzberg Pamela L. , Tsang John S. , Golding Hana ,   and the CHI Consortium, Biancotto Angelique , Candia Julián , Chen Jinguo , Cheung Foo , Dickler Howard , Kotliarov Yuri , Perl Shira , Shi Rongye , Stagliano Katherine E. R. , Young Neal S. , Zhou Huizhi
Published: August 2018

Immune responses to inactivated vaccines against avian influenza are poor due in part to lack of immune memory. Adjuvants significantly increased virus neutralizing titers. We performed comprehensive analyses of polyclonal antibody responses following FDA-approved adjuvanted H5N1-A/Indonesia vaccine, administered in presence or absence of AS03. Using Whole Genome Fragment Phage Display Libraries, we observed that AS03 induced antibody epitope diversity to viral hemagglutinin (HA) and neuraminidase compared with unadjuvanted vaccine. Furthermore, AS03 promoted significant antibody affinity maturation to properly folded H5-HA1 (but not to HA2) domain, which correlated with neutralization titers against both vaccine and heterologous H5N1 strains. However, no increase in heterosubtypic cross-neutralization of Group1-H1N1 seasonal strains was observed. AS03-H5N1 vaccine also induced higher neuraminidase inhibition antibody titers. This study provides insight into the differential impacts of AS03 adjuvant on H5N1 vaccine-induced antibody responses that may help optimize vaccine platforms for future vaccines with improved protection against seasonal and pandemic influenza strains.
Effect of unboiled water consumption data on sensitivity analysis in quantitative microbial risk assessment
Authors: Itoh Sadahiko , Zhou Liang
Published: August 2018

Quantitative microbial risk assessment of drinking water is generally followed by sensitivity analysis for examining the relative importance of variables of the simulation model on the outcome. This study investigated the effect of the statistical methods applied to unboiled water consumption data on sensitivity analysis. The sensitivity analysis for concentration of Escherichia coli (E. coli) in treated water showed completely different results from the analysis for E. coli dose. This was due to the application of a Poisson model to the water consumption, which suggested that 27% of the people did not drink tap water. Our study then applied a different model—an exponential distribution—to the water consumption data. In addition, incidental water intake was assigned to non-consumers in the Poisson model. The results of sensitivity analyses for these cases were very different from the ones obtained from the first analysis. This study therefore demonstrated that the statistical methods used to analyze water consumption data have great impacts on sensitivity analysis, although they do not affect the yearly risk of infection. Specifically, statistical methods may devalue sensitivity analysis. To avoid this problem, it is preferable to apply a continuous model such as the exponential model, rather than a discrete one such as the Poisson model, to describe the variability in water consumption.
Racial differences in Urinary Bladder Cancer in the United States
Authors: Wang Yu , Chang Qian , Li Yang
Published: August 2018

Urinary bladder cancer (UBC) has a high incidence rates in many southern and eastern European countries, in parts of Africa and the Middle East, and in North America. It exhibits a wide variety of histological types that goes from less aggressive to rapid-growing ones. In order to compare the different presentations, etiologies, and prognoses among racial groups, including NHW (non-Hispanic white), HW (Hispanic white), blacks, and API (Asian and Pacific Islander), we analyzed the UBC patients diagnosed between 1973 and 2014 using SEER (Surveillance, Epidemiology, and End Results) database. Patient characteristics, age-adjusted incidence rates, and survival were compared across races. There are significant racial differences in patients’ characteristics, including gender, marital status, age at diagnosis, treatment strategies, grade, stage, survival time, and so on. Overall, non-Hispanic whites have the highest incidence rate, followed by blacks, Hispanic whites, and APIs. In the analysis of survival, significant racial differences exist when stratified by gender, age group, histological type, stage, location and treatment strategies. Racial differences exist among UBC patients in the United States in terms of characteristics, incidence, and survival. Future studies may collect and analyze more data for comprehensive description and interpretation of the racial differences.
Mutant allele quantification reveals a genetic basis for TP53 mutation-driven castration resistance in prostate cancer cells
Authors: Lei Kefeng , Sun Ran , Chen Lee H. , Diplas Bill H. , Moure Casey J. , Wang Wenzhe , Hansen Landon J. , Tao Yulei , Chen Xufeng , Chen Chin-Pu Jason , Greer Paula K. , Zhao Fangping , Yan Hai , Bigner Darell D. , Huang Jiaoti , He Yiping
Published: August 2018

The concept that human cancer is in essence a genetic disease driven by gene mutations has been well established, yet its utilization in functional studies of cancer genes has not been fully explored. Here, we describe a simple genetics-based approach that can quickly and sensitively reveal the effect of the alteration of a gene of interest on the fate of its host cells within a heterogeneous population, essentially monitoring the genetic selection that is associated with and powers the tumorigenesis. Using this approach, we discovered that loss-of-function of TP53 can promote the development of resistance of castration in prostate cancer cells via both transiently potentiating androgen-independent cell growth and facilitating the occurrence of genome instability. The study thus reveals a novel genetic basis underlying the development of castration resistance in prostate cancer cells and provides a facile genetic approach for studying a cancer gene of interest in versatile experimental conditions.
Longitudinal characterization of nasopharyngeal colonization with Streptococcus pneumoniae in a South African birth cohort post 13-valent pneumococcal conjugate vaccine implementation
Authors: Dube Felix S. , Ramjith Jordache , Gardner-Lubbe Sugnet , Nduru Polite , Robberts F. J. Lourens , Wolter Nicole , Zar Heather J. , Nicol Mark P.
Published: August 2018

Monitoring changes in pneumococcal carriage is key to understanding vaccination-induced shifts in the ecology of carriage and impact on health. We longitudinally investigated pneumococcal carriage dynamics in infants. Pneumococcal isolates were obtained from nasopharyngeal (NP) swabs collected 2-weekly from 137 infants enrolled from birth through their first year of life. Pneumococci were serotyped by sequetyping, confirmed by Quellung. Pneumococci were isolated from 54% (1809/3331) of infants. Median time to first acquisition was 63 days. Serotype-specific acquisition rates ranged from 0.01 to 0.88 events/child-year and did not differ between PCV13 and non-PCV13 serotypes (0.11 events/child-year [95% CI 0.07–0.18] vs. 0.11 events/child-year [95% CI 0.06–0.18]). There was no difference in carriage duration between individual PCV13 and non-PCV13 serotypes (40.6 days [95% CI 31.9–49.4] vs. 38.6 days [95% CI 35.1–42.1]), however cumulatively the duration of carriage of non-PCV13 serotypes was greater than PCV13 serotypes (141.2 days (95% CI 126.6–155.8) vs. 30.7 days (95% CI 22.3–39.0). Frequently carried PCV13 serotypes included 19F, 9V, 19A and 6A, while non-PCV13 serotypes included 15B/15C, 21, 10A, 16F, 35B, 9N and 15A. Despite high immunization coverage in our setting, PCV13 serotypes remain in circulation in this cohort, comprising 22% of isolates. Individual PCV13 serotypes were acquired, on average, at equivalent rate to non-PCV13 serotypes, and carried for a similar duration, although the most common non-PCV13 serotypes were more frequently acquired than PCV13 serotypes.
Unique resistance traits against downy mildew from the center of origin of grapevine (Vitis vinifera)
Authors: Toffolatti Silvia Laura , De Lorenzis Gabriella , Costa Alex , Maddalena Giuliana , Passera Alessandro , Bonza Maria Cristina , Pindo Massimo , Stefani Erika , Cestaro Alessandro , Casati Paola , Failla Osvaldo , Bianco Piero Attilio , Maghradze David , Quaglino Fabio
Published: August 2018

The Eurasian grapevine (Vitis vinifera), an Old World species now cultivated worldwide for high-quality wine production, is extremely susceptible to the agent of downy mildew, Plasmopara viticola. The cultivation of resistant V. vinifera varieties would be a sustainable way to reduce the damage caused by the pathogen and the impact of disease management, which involves the economic, health and environmental costs of frequent fungicide application. We report the finding of unique downy mildew resistance traits in a winemaking cultivar from the domestication center of V. vinifera, and characterize the expression of a range of genes associated with the resistance mechanism. Based on comparative experimental inoculations, confocal microscopy and transcriptomics analyses, our study shows that V. vinifera cv. Mgaloblishvili, native to Georgia (South Caucasus), exhibits unique resistance traits against P. viticola. Its defense response, leading to a limitation of P. viticola growth and sporulation, is determined by the overexpression of genes related to pathogen recognition, the ethylene signaling pathway, synthesis of antimicrobial compounds and enzymes, and the development of structural barriers. The unique resistant traits found in Mgaloblishvili highlight the presence of a rare defense system in V. vinifera against P. viticola which promises fresh opportunities for grapevine genetic improvement.
Gut microbiota composition and butyrate production in children affected by non-IgE-mediated cow’s milk allergy
Authors: Berni Canani Roberto , De Filippis Francesca , Nocerino Rita , Paparo Lorella , Di Scala Carmen , Cosenza Linda , Della Gatta Giusy , Calignano Antonio , De Caro Carmen , Laiola Manolo , Gilbert Jack A. , Ercolini Danilo
Published: August 2018

Cow’s milk allergy (CMA) is one of the earliest and most common food allergy and can be elicited by both IgE- or non-IgE-mediated mechanism. We previously described dysbiosis in children with IgE-mediated CMA and the effect of dietary treatment with extensively hydrolyzed casein formula (EHCF) alone or in combination with the probioticLactobacillus rhamnosusGG (LGG). On the contrary, the gut microbiota in non-IgE-mediated CMA remains uncharacterized. In this study we evaluated gut microbiota composition and fecal butyrate levels in children affected by non-IgE-mediated CMA. We found a gut microbiota dysbiosis in non-IgE-mediated CMA, driven by an enrichment ofBacteroidesandAlistipes. Comparing these results with those previously obtained in children with IgE-mediated CMA, we demonstrated overlapping signatures in the gut microbiota dysbiosis of non-IgE-mediated and IgE-mediated CMA children, characterized by a progressive increase inBacteroidesfrom healthy to IgE-mediated CMA patients. EHCF containg LGG was more strongly associated with an effect on dysbiosis and on butyrate production if compared to what observed in children treated with EHCF alone. If longitudinal cohort studies in children with CMA will confirm these results, gut microbiota dysbiosis could be a relevant target for innovative therapeutic strategies in children with non-IgE-mediated CMA.
Secreted products of oral bacteria and biofilms impede mineralization of apical papilla stem cells in TLR-, species-, and culture-dependent fashion
Authors: Petridis Xenos , van der Sluis Luc W. M. , Dijkstra René J. B. , Brinker Marja G. L. , van der Mei Henny C. , Harmsen Martin C.
Published: August 2018

Regenerative endodontics exploits the mineralization potential of stem cells from the apical papilla (SCAPs) in order to promote root maturation of permanent immature teeth. SCAPs may encounter post-disinfection residual bacteria either in planktonic or in biofilm growth mode. Bacterial components bind to Toll-like receptors (TLRs) and trigger pro-inflammatory responses. We hypothesized that biofilm-triggered TLR activation affects the mineralization potential of human SCAPs. SCAPs were challenged with conditioned media derived from standardized dual-species biofilms and planktonic bacterial cultures and their inflammatory status and mineralization capacity were studied. Bacterial products from both growth modes (planktonic vs. biofilm) compromised cell viability, proliferation and mineralization capacity of SCAPs, but in a species- and growth mode-dependent fashion. While TLR4 expression remained unaffected, TLR2 expression was upregulated coinciding with a pro-inflammatory activation of SCAPs. Moreover, TLR and its downstream TGF-β-associated kinase (TAK1) appeared to be blocking mineralization, as inhibition of these factors restored it. In conclusion, bacterial products promoted the pro-inflammatory status and inhibited mineralization of human SCAPs in a TLR-, species-, and culture-dependent fashion. TLR2 emerged as the pivotal mediator of these responses and further research is warranted towards the judicious manipulation of SCAPs in order to modify the untoward events of TLR-priming and signaling.
The small heat shock protein HSPB1 protects mice from sepsis
Authors: Breed Elise R. , Hilliard Carolyn A. , Yoseph Benyam , Mittal Rohit , Liang Zhe , Chen Ching-Wen , Burd Eileen M. , Brewster Luke P. , Hansen Laura M. , Gleason Rudolph L. , Pandita Tej K. , Ford Mandy L. , Hunt Clayton R. , Coopersmith Craig M.
Published: August 2018

In vitro studies have implicated the small heat shock protein HSPB1 in a range of physiological functions. However, its in vivo relevance is unclear as the phenotype of unstressed HSPB1−/− mice is unremarkable. To determine the impact of HSPB1 in injury, HSPB1−/− and wild type (WT) mice were subjected to cecal ligation and puncture, a model of polymicrobial sepsis. Ten-day mortality was significantly higher in HSPB1−/− mice following the onset of sepsis (65% vs. 35%). Ex vivo mechanical testing revealed that common carotid arteries from HSPB1−/− mice were more compliant than those in WT mice over pressures of 50–120 mm Hg. Septic HSPB1−/− mice also had increased peritoneal levels of IFN-γ and decreased systemic levels of IL-6 and KC. There were no differences in frequency of either splenic CD4+ or CD8+ T cells, nor were there differences in apoptosis in either cell type. However, splenic CD4+ T cells and CD8+ T cells from HSPB1−/− mice produced significantly less TNF and IL-2 following ex vivo stimulation. Systemic and local bacterial burden was similar in HSPB1−/− and WT mice. Thus while HSPB1−/− mice are uncompromised under basal conditions, HSPB1 has a critical function in vivo in sepsis, potentially mediated through alterations in arterial compliance and the immune response.
Binding kinetics of cariprazine and aripiprazole at the dopamine D3 receptor
Authors: Frank Annika , Kiss Dóra J. , Keserű György M. , Stark Holger
Published: August 2018

The dissociation behaviours of aripiprazole and cariprazine at the human D2 and D3 receptor are evaluated. A potential correlation between kinetics and in vivo profiles, especially cariprazine’s action on negative symptoms in schizophrenia, is investigated. The binding kinetics of four ligands were indirectly evaluated. After the receptor preparations were pre-incubated with the unlabelled ligands, the dissociation was initiated with an excess of [3H]spiperone. Slow dissociation kinetics characterizes aripiprazole and cariprazine at the D2 receptor. At the D3 receptor, aripiprazole exhibits a slow monophasic dissociation, while cariprazine displays a rapid biphasic behaviour. Functional ß-arrestin assays and molecular dynamics simulations at the D3 receptor confirm a biphasic binding behaviour of cariprazine. This may influence its in vivo action, as the partial agonist could react rapidly to variations in the dopamine levels of schizophrenic patients and the ligand will not quantitatively dissociate from the receptor in one single step. With these findings novel agents may be developed that display rapid, biphasic dissociation from the D3R to further investigate this effect on in vivo profiles.