bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuer Diagnosestandard bei Verdacht auf Diabetes insipidus
Authors: Chifu Irina , Fenske Wiebke
Published: December 2018

Was ist neu?

Ursachen und klinische Manifestation Es gilt 3 Hauptentitäten des Polyurie-Polydipsie-Syndroms zu differenzieren, die sich ursächlich wie auch in ihrer Behandlung klar unterscheiden. Die häufigste Form dieser Entität ist der Diabetes insipidus centralis, bei dem die osmosensitive Freisetzung von AVP (Arginin Vasopressin Peptid) aus der Neurohypophyse gestört ist. Bei der viel seltener vorliegenden Form des renalen oder nephrogenen Diabetes insipidus liegt eine Insensitivität der AVP-vermittelten Antidiurese in den Nieren vor. Die 3. Form, die unterschieden wird, ist die primäre Polydipsie. Sie entsteht oft durch eine Suppression der AVP-Freisetzung durch einen exzessiv gesteigerten Flüssigkeitskonsum.

Diagnostik – der indirekte Durstversuch Als Referenzstandard in der Diagnostik des Polyurie-Polydipsie-Syndroms galt bisher der indirekte Durstversuch. Dieser bestimmt seriell das Harnvolumen und die Harnkonzentration (als indirekte Parameter) zur Einschätzung des funktionellen Harnkonzentrationsvermögens. Der indirekte Durstversuch ist allerdings in seiner diagnostischen Zuverlässigkeit limitiert. Die Identifizierung der intermediären Manifestation – die Erfassung von Patienten mit primärer Polydipsie und deren Differenzierung von Patienten mit partiellem zentralem oder renalem Diabetes insipidus – ist eine besondere Herausforderung.

Diagnostik – direkte Erfassung des AVP-Surrogats-Copeptin 2018 bringt nun neue Erkenntnisse in der Diagnostik. Copeptin hat in den letzten Jahren zur Differenzierung der hypotonen Polyurie zunehmend an Bedeutung gewonnen. Aktuelle Studien zeigen, dass Plasma-Copeptin einen stabilen und osmotisch-sensitiven Surrogatmarker des technisch schwer zu messenden bioaktiven antidiuretischen Hormons AVP (Arginin Vasopressin Peptid) darstellt. Die zuverlässige Erfassung des nephrogenen Diabetes insipidus anhand einer einzigen Copeptin-Messung ohne Flüssigkeitskarenz ist mittlerweile etabliert und gehört vielerorts bereits zur klinischen Routinediagnostik. Eine kürzlich veröffentlichte internationale prospektive Studie untersuchte nun die diagnostische Zuverlässigkeit von Plasma-Copeptin unter osmotischer Stimulation mit einer 3 %-NaCl-Infusion zur gezielten Differenzierung zwischen Patienten mit zentralem Diabetes insipidus und einer primären Polydipsie. Dieses Verfahren wird künftig – so die Prognose des Editorials im New England Journal of Medicine – zum neuen diagnostischen Referenzstandard zur Abklärung von Patienten mit einer hypotonen Polyurie avancieren.
COPD durch berufliche Noxen
Authors: Baur X.
Published: December 2018

Die chronisch obstruktive Lungenerkrankung (COPD), charakterisiert durch eine großteils nicht reversible bronchiale Obstruktion mit Flusslimitierung und typischerweise progredientem Verlauf, zählt weltweit zu den führenden Ursachen der Morbidität und Mortalität. Neben dem ursächlich im Vordergrund stehenden Zigarettenrauchen und Umweltexpositionen (v. a. Abbrennen organischer Materialien an offenen Kochstellen) sind in etwa 15 % berufliche Schadstoffexpositionen und eher selten (ca. 6 %) keine exogenen Faktoren festzustellen. Berufliche Auslöser werden häufig infolge unzureichender arbeitsanamnestischer Erhebungen übersehen. Dies wird insbesondere in der Diskrepanz zwischen den in einer Reihe von Studien belegten Prävalenzen und Inzidenzen und den laut Berufskrankheitenstatistik relativ niedrigen Anzeigezahlen, Anerkennungen und Entschädigungen deutlich. Eine Herausforderung stellt im Einzelfall die Frage dar, ob, neben außerberuflichen Faktoren (zum Beispiel Rauchen), beruflichen Schadstoffbelastungen eine im Rechtssinn wesentliche Teilursache zukommt. Anhand von Fallberichten wird auf neuere Entscheidungen der Sozialgerichtsbarkeit in solchen Fällen eingegangen.
TAVI: GKV-Routinedatenanalyse zu Marktdurchdringung und
Implikationen einer medizintechnischen Innovation
Authors: Schneider Udo , Schmid Andreas , Linder Roland , Verheyen Frank
Published: December 2018

Zielsetzung Interventionen mit kathetergestütztem Aortenklappenersatz
(TAVI: Trans-catheter aortic valve implantation) nehmen in Deutschland
kontinuierlich zu. Im Jahr 2013 lag die Zahl erstmals über jener für
konventionelle Eingriffe (Aortenklappenersatz, AKE). Für Patienten mit
Aortenklappenstenose, insbesondere inoperable ältere und Hochrisikopatienten,
stellt TAVI eine mit geringeren Belastungen einhergehende – wenn auch teurere –
Alternative zum AKE dar.

Methodik Vor diesem Hintergrund wird erstens die Verbreitung der TAVI im
Zeitablauf in Deutschland analysiert. Zweitens wird untersucht, ob Empfehlungen
des G-BA hinsichtlich einer institutionalisierten herzchirurgischen
Fachabteilung befolgt werden. Der Analyse liegen Routinedaten der Techniker
Krankenkasse (TK) für die Jahre 2009–2015 zugrunde.

Ergebnisse Für TAVI lag die Häufigkeit pro 100 000 Versicherten 2015 bei
9,2 (+ 457 % zu 2009), für AKE bei 18,7 (+ 10,6 %). Der TAVI-Anteil an allen
Eingriffen stieg stetig an, wobei eine zunehmende Verbreitung auch in dünn
besiedelten Gebieten zu beobachten ist. In ca. 10 % der Krankenhäuser, in denen
TAVI durchgeführt wurden, gab es keine institutionalisierte herzchirurgische
Abteilung. Während im Jahr 2009 Eingriffe in knapp der Hälfte aller Häuser
ausschließlich im konventionellen Verfahren erfolgten, sank dieser Anteil bis
zum Jahr 2015 auf 5 Prozent. Gleichzeitig wurden in ca. 15 Prozent nur noch
TAVI-Eingriffe durchgeführt. Die Daten zeigen eine Abkehr vom alleinigen Angebot
offen-chirurgischer Aortenklappeneingriffe hin zu einem in der Mehrheit dualem
Angebot beider Methoden.
Gestational Diabetes Mellitus in a Tertiary Care Hospital of Kolkata,
India: Prevalence, Pathogenesis and Potential Disease Biomarkers
Authors: Basu Jayita , Datta Chhanda , Chowdhury Subhankar , Mandal Debasmita , Mondal Nandan Kumar , Ghosh Amlan
Published: December 2018

Aims Prevalence of gestational diabetes mellitus (GDM) may vary
across a country like India. Risk factors and disease-pathogenesis were also
not fully elucidated. This study aimed to examine prevalence of GDM among
pregnant women visiting antenatal clinic of a tertiary-care hospital of
Kolkata, India; possible mechanism of disease pathogenesis and potency of
associated parameters as disease biomarkers were also explored.

Methods 735 pregnant women were screened for GDM according to DIPSI
(Diabetes in Pregnancy Study Group India) guideline and risk-factors were
analyzed. Case-control study was conducted with 114 GDM and 114 matched
non-GDM control. Blood sample was collected before glucose load for complete
blood count, measurement of reactive oxygen species (ROS) and assessment of
DNA damage.

Results Prevalence of GDM was found to be
17.2%(127/735). Maternal age, diabetic family history and
acanthosis nigricans seemed to be important risk factors. Total ROS,
lymphocyte DNA damage (measured by comet-assay) and some inflammatory
hematological parameters were significantly higher in GDM compared to
control. ROS, comet-tail DNA%, WBC, neutrophil-lymphocyte ratio
(NLR) and mean platelet volume (MPV) were established as independent
determinants of disease condition after adjustment for pre-gestational body
mass index. In receiver operating characteristic analysis, ROS>155.7
arbitrary fluorescent unit, NLR>2.12 and
MPV>11.05 fL showed 82.5 & 98.2%, 71.9
& 84.2% and 71.9 & 82.5% sensitivity
& specificity respectively in disease prediction.

Conclusions Prevalence of GDM seemed to be high in Kolkata on Indian
scenario. Oxidative-stress, related DNA-damage and inflammation seemed to
have important contribution in pathogenesis of GDM independent of obesity.
ROS, NLR and MPV with respective cut-off scores might be used as diagnostic
and prognostic biomarkers for better management of the disease.
Synthesis of Naphthoic Acids as Potential Anticancer Agents
Authors: Deck Lorraine , Greenberg Jacob , Whalen Lisa , Vander Jagt David , Royer Robert
Published: December 2018

As part of ongoing research to investigate structural requirements for lactate dehydrogenase inhibition by highly substituted naphthoic acids, nine new aryl-substituted dihydroxynaphthoic acids were synthesized from three known precursors. Described here are efficient preparations of the 1-naphthoic acid target compounds by using Suzuki coupling reactions, formylations, oxidations, and demethylations. Lactate dehydrogenase inhibition studies conducted with five of the compounds revealed values of the inhibitory constant K
i in the low micromolar range.
Palladium-Catalyzed Synthesis of β,β-Diaryl α,β-Unsaturated Ketones
Authors: Shao Li-ming , Zheng Yi-lin , Xiao Li , Xie Qiong
Published: December 2018

We herein describe a versatile palladium-catalyzed synthesis of β,β-diaryl α,β-unsaturated ketones. A broad range of aryl halides react with β-arylbutanones to afford biologically useful, symmetrical and unsymmetrical ketones. The use of 4,5-diazafluoren-9-one and oxygen makes this one-pot reaction more applicable. A plausible mechanism involving palladium-catalyzed oxidative Heck-type cross-coupling is also proposed.
C3-Allylation of Indoles via an Iridium-Catalyzed Branch-Selective Ring-Opening Reaction of Vinylcyclopropanes
Authors: Mei Guang-Jian , Shi Feng , Yu Lei , Zhu Zi-Qi , Sun Meng
Published: December 2018

An iridium-catalyzed branch-selective ring-opening reaction of vinylcyclopropanes with indoles has been established, which afforded C3-allylindoles in generally good to excellent yields (up to 95%). Considering that no wastes were generated in the whole process and branch-selective ring-opening reaction of vinylcyclopropanes was rarely reported, this strategy not only can be regarded as a highly atom-economic approach for C3-allylindoles, but also will greatly enrich the chemistry of vinylcyclopropanes.
Cesium Carbonate-Promoted P-Alkylation of Phosphinecarboxamides
Authors: Quan Zheng-Jun , Chen Xing-Guo , Wu Qiu-Li , Hou Fei , Wang Xi-Cun
Published: December 2018

An effective method for the P-alkylation of N-arylphosphinecarboxamides was demonstrated. Primary N-arylphosphinecarboxamides without additional protection underwent P-monoalkylation with various alkyl halides in the presence of cesium carbonate as a promoter. The reactivity of phosphinecarboxamides was also explored.
German Heart Surgery Report 2017: The Annual Updated Registry of the German Society for Thoracic and Cardiovascular Surgery
Authors: Meyer Renate , Lewandowski Jana , Frie Michael , Markewitz Andreas , Harringer Wolfgang , Beckmann Andreas
Published: December 2018

Based on a longtime voluntary registry, founded by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS), well-defined data of all cardiac, thoracic, and vascular surgery procedures performed in 78 German heart surgery departments during the year 2017 are analyzed. In 2017, a total of 179,337 procedures were submitted to the registry, and 101,728 were summarized as heart surgery procedures in the narrower sense. About 16.8% of these patients were at least 80 years old, resulting in an increase of 1.1% compared with the data of 2016. The 36,273 isolated coronary artery bypass grafting procedures (relationship on-/off-pump 4.2:1) were associated with an unadjusted in-hospital survival rate of 97.3%. Concerning the 34,394 isolated heart valve procedures (including 12,965 transcatheter interventions), the unadjusted in-hospital survival rate was 96.0%.

This annual updated registry of the GSTCVS represents voluntary public reporting by accumulating actual information for nearly all heart surgical procedures in Germany, describes advancements in heart medicine, and is a basis for in- and external quality assurance for all participating institutions. In addition, the registry demonstrates that the provision of cardiac surgery in Germany is appropriate, and nationwide patient treatment is guaranteed at any time.
Minitwistors and 3d Yang-Mills-Higgs theory
Authors: Adamo Tim , Skinner David , Williams Jack
Published: December 2018

We construct a minitwistor action for Yang–Mills–Higgs (YMH) theory in three dimensions. The Feynman diagrams of this action will construct perturbation theory around solutions of the Bogomolny equations in much the same way that MHV (maximally helicity violating) diagrams describe perturbation theory around the self-dual Yang Mills equations in four dimensions. We also provide a new formula for all tree amplitudes in YMH theory (and its maximally supersymmetric extension) in terms of degree d maps to minitwistor space. We demonstrate its relationship to the Roiban-Spradlin-Volovich-Witten (RSVW) formula in four dimensions and show that it generates the correct MHV amplitudes at d = 1 and factorizes correctly in all channels for all degrees.
Soliton-generating τ-functions revisited
Authors: Zarmi Yair
Published: December 2018

In the inverse-scattering formalism and the Hirota algorithm, soliton solutions of evolution equations are images of τ-functions, which are, often, unbounded in space and time. Hence, whereas solitons are bounded, localized structures, they are generated from unbounded, spatially extended entities that lack physically intuitive significance. The goal of this paper is to provide a representation of soliton solutions as images of bounded and localized sources. To this end, appropriate equivalent τ-functions, which are different in form from the traditionally used ones, are generated. In terms of the latter, the single-soliton solutions of the Korteweg-deVries (KdV) and Kadomtsev-Petviashvili II (KP II) equations are images of single solitons (NOT solutions of theses equations), whereas multi-soliton solutions are images of positive humps that are localized in the soliton interaction region. The structure of the equivalent τ-functions has another desirable attribute: It elucidates in a simple manner the role of the arbitrary shifts in the positions of soliton trajectories in controlling the behavior of multi-soliton solutions: Whether an N-soliton solution is reduced to a solution with (N − 1) or (N − 2) solitons when two wave numbers are made to coincide. Examples are discussed in the cases of the KdV and KP II equations. The modified KdV equation provides a unique observation. Depending on the shifts in the positions of soliton trajectories, when two wave numbers are made to coincide, the two-soliton solution may tend either to a single soliton or to a δ-function in the x-t plane.
Effect of indium and antimony doping on the transport properties of direct vapour transport (DVT) grown SnSe single crystals
Authors: Patel Shivam , Chaki S. H. , Vinodkumar P. C.
Published: December 2018

Pure SnSe, 5% In, 10% In, 5% Sb, and 10% Sb doped SnSe single crystals were grown by the direct vapour transport technique. The energy dispersive X-ray analysis study of the samples showed them to be near stoichiometric but slightly Sn deficient. The X-ray diffraction study of all the as-grown single crystal samples showed that they possess an orthorhombic structure and the lattice parameters are in good agreement with the reported parameters. The thermoelectric power (S), dc electrical conductivity (σ), and thermal conductivity (κ) variation with temperature from ambient to 573 K substantiated the semiconducting nature of all the five samples. The sign of “S” was positive for all five samples for all the temperature range stating the sample to be a p-type semiconductor. The power factor (S2σ) and figure of merit (ZT) variation with temperature showed that pure SnSe possesses the highest value compared to doped samples. The obtained results are studied and discussed in detail.
A many-body dissipative particle dynamics study of nanoneedle-liquid interface
Authors: Falsafi Ali , Nejat Pishkenari Hossein
Published: December 2018

The wetting of solid surfaces plays an important role in the operation of many natural and engineering systems, for instance, Trolling mode Atomic Force Microscopy whose imaging is definitely affected by a wetting phenomenon. The purpose of this paper is to present a better understanding of the meniscus formation on the outer surface of a nanoneedle. To investigate the wetting process at the micro- and nanoscales, where the experimental observations do not provide rigorous realization, theoretical approaches with their capability to model and predict the system behavior with atomic details can be utilized. To study the time-evolution of the nanomeniscus formation in the solid-liquid interface, an appropriate coarse graining method, called many-body dissipative particle dynamics, is employed. We investigated the correlation between the nanoneedle diameter and nanomeniscus characteristics such as contact angle, meniscus height, evanescent length, and interaction forces. In addition, the effect of a potential parameter, as a means for adjusting the degree of needle wall's wettability, on the meniscus geometry and interaction forces is evaluated. The results of this research have different applications in various fields, such as Trolling-mode AFM and rheological measurements.
Rewetting and boiling in jet impingement on high temperature steel surface
Authors: Leocadio H. , van der Geld C. W. M. , Passos J. C.
Published: December 2018

Interface topologies and boiling phenomena are observed within the water jet impingement zone during quenching of a high temperature (300 °C–900 °C) steel plate by direct optical observations. Stable film boiling may occur, but surface asperities may easily penetrate the vapor film and interact with the flowing liquid. By cooling down more rapidly than the remaining solid surface, such asperities act as a kind of micro-fin. Rather surprisingly, non-coalescing bubbles on top of the thin vapor film have been observed, probably formed on top of penetrating surface asperities. After establishing contact between water and solid, so after rewetting, an intense bubble activity is normally seen of bubbles that are footed on a dry plate area with a contact line reflecting the light-emitting diode lights and condensing at later times. These are vapor bubbles. A high surface roughness promotes rewetting that may be initiated at several places simultaneously. For an initial plate temperature of 300 °C and a total height roughness of 5 μm, rewetting took place without the occurrence of a vapor film; surfaces at or above 450 °C exhibited vapor film formation, even for a high jet subcooling of 80 °C. Temperature and time of rewetting are strongly affected by the initial surface temperature and jet subcooling and less by the jet velocity. New correlations are provided to predict these dependencies.
The origin of carbon-related carrier compensation in p-type GaN layers grown by MOVPE
Authors: Narita Tetsuo , Tomita Kazuyoshi , Tokuda Yutaka , Kogiso Tatsuya , Horita Masahiro , Kachi Tetsu
Published: December 2018

The role of carbon impurities in p-type GaN layers grown by metalorganic vapor phase epitaxy (MOVPE) was investigated. The lightly Mg-doped (∼1017 cm−3) p-type GaN samples with different carbon concentration [C] were prepared by controlling growth temperature and pressure. Temperature-dependent Hall-effect analyses exhibited an increase in donor concentration with increasing [C]. The low-temperature mobility also decreased with increasing [C], as a result of mobility limitation due to ionized impurity scattering. These results show that carbon atoms in MOVPE-grown p-GaN layers act as ionized donors and cause carrier compensation. Deep-level transient spectroscopy (DLTS) using bias pulses detected the existence of Hd traps (EV +0.88 eV) arising from the 0/−1 charge state of carbon on nitrogen sites (CN). The concentrations of Hd traps closely corresponded to [C] values in p-type GaN layers. Employing low-frequency capacitance DLTS to avoid carrier freeze-out at low temperatures, we newly discovered the Ha trap (EV +0.29 eV) whose concentration was directly proportional to the [C] value. These findings suggest that the Ha trap originates from CN identical to the Hd trap. Based on prior theoretical calculations of energy levels, the Ha trap can reasonably be assigned to a +1/0 donor state of CN. These results strongly suggest that a CN having two different charged states can compensate an electron and a hole in n-type and p-type GaN layers, respectively.
Ultra-fast adaptive optical micro-lens arrays based on stressed liquid crystals
Authors: Kurochkin O. , Buluy O. , Varshal J. , Manevich M. , Glushchenko A. , West J. L. , Reznikov Yu. , Nazarenko V.
Published: December 2018

We characterized the optical properties of a photoresist-based micro-lens using a stressed liquid crystal matrix for high-speed variation of the focal distance. We also determined the operational parameters for the adaptive optical spherical and cylindrical micro-lens arrays. The resulting optical elements feature fast response times, around 1 ms, with a focal length range of 2600-970 μm.
Reverse-time-migration imaging for a crack in a thin plate by dispersed flexural waves
Authors: Gao Xiang , Li Jian , Ma Jun , Li Junhong , Cheng Jianzheng , Wang Chenghao
Published: December 2018

A modified reverse time migration (RTM) method for dispersed flexural waves is proposed to detect and image the crack in a thin plate. The key point of this method is to take the time reversal (TR) of the expanded flexural wave at a receiver as the backward wave in the cross-correlation imaging condition of RTM, thus the expanded backward wave will be re-compressed also due to dispersion of the flexural wave. The backward wave is time reversed again when arriving at a certain point on the plate, and then correlated to the forward wave derived from the original source. The image of the crack is obtained by superimposing the cross-correlation results of many source-receiver pairs in transmitting and receiving arrays. The experimental studies on imaging a crack in a thin plate are conducted, and the transmitted and received waveforms are recorded with high fidelity by a laser vibrometer, thus, ensuring that an accurate and clear image of the crack is obtained by this modified RTM process.
Novel Cas9-nickase technique repairs mutation without off-target modifications
Authors: Liebendorfer Adam
Published: December 2018

On-target mutagenesis while combining Cas9-nickase with a piggyBac transposon-modified donor vector to repair beta-thalassemia mutations highlights advances and new concerns for CRISPR-Cas systems.
Contractions in hydrogels point to biochemical clues of valvular disorders
Authors: Liebendorfer Adam
Published: December 2018

A new technique using poly(ethylene glycol) hydrogels has allowed researchers to quantify how treatments affect the behavior of valvular interstitial cells.
Effect of banana flower powder on rumen fermentation, synthesis of microbial protein and nutrient digestibility in swamp buffaloes
Authors: Wanapat Metha , Ampapon Thiwakorn , Phesatcha Kampanat , Kang Sungchhang
Published: December 2018

Replacement of chemical compounds by dietary sources as rumen enhancers have been of great interest and concern by researchers. Four, rumen-fistulated swamp buffalo bulls with average liveweight of 365 ± 15.0 kg were randomly assigned to treatments, to investigate the impact of banana flower powder (BAFLOP) as a rumen modifier on pH, rumen fermentation, nutrient digestibility, microbial protein synthesis and volatile fatty acids. All buffaloes were allotted according to a 4 × 4 Latin square design. Dietary supplementation treatments were as follows: 2 g concentrate/kg bodyweight (BW; T1), 15 g concentrate/kg BW (T2), 15 g concentrate/kg BW plus BAFLOP 300 g/head.day (T3) and 15 g concentrate/kg BW plus BAFLOP 600 g/head.day (T4). Untreated rice straw was fed ad libitum. The findings showed that total feed intake was increased in buffaloes fed a diet supplemented with concentrate at 2 g/kg BW, while rice straw intake was reduced. Nutrient digestibility was increased by BAFLOP supplementation at both levels (T3 and T4; P < 0.05). Ruminal pH dropped (5.9) in buffaloes fed with concentrate at 15 g/kg BW, while buffaloes with BAFLOP supplementation could maintain ruminal pH when fed with high-concentrate diet. Ruminal ammonia-nitrogen increased in the buffaloes fed concentrate at 15 g/kg BW, especially with BAFLOP supplementation. Feeding high-concentrate diet increased the concentrations of ruminal total volatile fatty acids and propionic acid (C3), while the concentration of acetic acid and the acetic acid:C3 ratio and methane production were subsequently reduced (P < 0.05). In addition, efficiency of microbial protein synthesis was increased by the BAFLOP feeding (P < 0.05). In the present study, using BAFLOP as a dietary rumen enhancer at 300–600 g/head.day resulted in an increased rumen pH, C3 concentration, nutrient digestibility and microbial protein synthesis, while mitigating ruminal methane production. Higher nutrient digestibility and lower ruminal methane production, more dietary energy and production efficiency are expected.
Morphometric and gene expression analyses of stromal expansion during development of the bovine fetal ovary
Authors: Hartanti M. D. , Hummitzsch K. , Irving-Rodgers H. F. , Bonner W. M. , Copping K. J. , Anderson R. A. , McMillen I. C. , Perry V. E. A. , Rodgers R. J.
Published: December 2018

During ovarian development stroma from the mesonephros penetrates and expands into the ovarian primordium and thus appears to be involved, at least physically, in the formation of ovigerous cords, follicles and surface epithelium. Cortical stromal development during gestation in bovine fetal ovaries (n=27) was characterised by immunohistochemistry and by mRNA analyses. Stroma was identified by immunostaining of stromal matrix collagen type I and proliferating cells were identified by Ki67 expression. The cortical and medullar volume expanded across gestation, with the rate of cortical expansion slowing over time. During gestation, the proportion of stroma in the cortex and total volume in the cortex significantly increased (P<0.05). The proliferation index and numerical density of proliferating cells in the stroma significantly decreased (P<0.05), whereas the numerical density of cells in the stroma did not change (P>0.05). The expression levels of 12 genes out of 18 examined, including osteoglycin (OGN) and lumican (LUM), were significantly increased later in development (P<0.05) and the expression of many genes was positively correlated with other genes and with gestational age. Thus, the rate of cortical stromal expansion peaked in early gestation due to cell proliferation, whilst late in development expression of extracellular matrix genes increased.
Article Commentary: Commentary on the 40th Anniversary of AMERSA: Amersa at 40: How it all Began and How it Survived
Authors: Lewis David , Schnoll Sidney H.
Published: December 2018

The question at hand for the 40th anniversary of AMERSA is how an organization with such a small membership devoted to substance use disorder medical education actually survived for 40 years. There were many obstacles. AMERSA had limited resources and only modest outside support. It was surrounded by large addiction specialty medical organizations with large budgets, some with membership in the thousands. Further, the missions of these larger organizations included medical education. Our longevity can be ascribed to these four critical periods and events. The Career Teacher Program (1972-1981), The decision by AMERSA in 1983 to remain an independent national organization, The AMERSA standard setting conference of 1985, AMERSA's Strategic Plan for Interdisciplinary Faculty Development and Project Mainstream (1999-2003).
Vaccines: An achievement of civilization, a human right, our health insurance for the future
Authors: Rappuoli Rino , Santoni Angela , Mantovani Alberto
Published: December 2018

Vaccines have made a key, cost-effective contribution to the prolongation of life expectancy and quality. Here we summarize challenges facing vaccinology and immunology at the level of society, scientific innovation, and technology in a global health perspective. We argue that vaccines represent a safety belt and life insurance for humankind.
Empiric Antibiotic Treatment Thresholds for Serious Bacterial Infections: A Scenario-based Survey Study
Authors: Cressman Alex M , MacFadden Derek R , Verma Amol A , Razak Fahad , Daneman Nick
Published: December 2018

Background

Physicians face competing demands of maximizing pathogen coverage while minimizing unnecessary use of broad-spectrum antibiotics when managing sepsis. We sought to identify physicians’ perceived likelihood of coverage achieved by their usual empiric antibiotic regimen, along with minimum thresholds of coverage they would be willing to accept when managing these patients.

Methods

We conducted a scenario-based survey of internal medicine physicians from across Canada using a 2 × 2 factorial design, varied by infection source (undifferentiated vs genitourinary) and severity (mild vs severe) denoted by the Quick Sequential Organ Failure Assessment (qSOFA) score. For each scenario, participants selected their preferred empiric antibiotic regimen, estimated the likelihood of coverage achieved by that regimen, and considered their minimum threshold of coverage.

Results

We had 238 respondents: 87 (36.6%) residents and 151 attending physicians (63.4%). The perceived likelihood of antibiotic coverage and minimum thresholds of coverage (with interquartile range) for each scenario were as follows: (1) severe undifferentiated, 90% (89.5%–95.0%) and 90% (80%–95%), respectively; (2) mild undifferentiated, 89% (80%–95%) and 80% (70%–89.5%); (3) severe genitourinary, 91% (87.3%–95.0%) and 90% (80.0%–90.0%); and (4) mild genitourinary, 90% (81.8%–91.3%) and 80% (71.8%–90%). Illness severity and infectious disease specialty predicted higher thresholds of coverage whereas less clinical experience and lower self-reported prescribing intensity predicted lower thresholds of coverage.

Conclusions

Pathogen coverage of 80% and 90% are physician-acceptable thresholds for managing patients with mild and severe sepsis from bacterial infections. These data may inform clinical guidelines and decision-support tools to improve empiric antibiotic prescribing.
Multi-scale analysis of schizophrenia risk genes, brain structure, and clinical symptoms reveals integrative clues for subtyping schizophrenia patients
Authors: Ma Liang , Rolls Edmund T , Liu Xiuqin , Liu Yuting , Jiao Zeyu , Wang Yue , Gong Weikang , Ma Zhiming , Gong Fuzhou , Wan Lin
Published: December 2018

Analysis linking directly genomics, neuroimaging phenotypes and clinical measurements is crucial for understanding psychiatric disorders, but remains rare. Here, we describe a multi-scale analysis using genome-wide SNPs, gene expression, grey matter volume (GMV), and the positive and negative syndrome scale scores (PANSS) to explore the etiology of schizophrenia. With 72 drug-naive schizophrenic first episode patients (FEPs) and 73 matched heathy controls, we identified 108 genes, from schizophrenia risk genes, that correlated significantly with GMV, which are highly co-expressed in the brain during development. Among these 108 candidates, 19 distinct genes were found associated with 16 brain regions referred to as hot clusters (HCs), primarily in the frontal cortex, sensory-motor regions and temporal and parietal regions. The patients were subtyped into three groups with distinguishable PANSS scores by the GMV of the identified HCs. Furthermore, we found that HCs with common GMV among patient groups are related to genes that mostly mapped to pathways relevant to neural signaling, which are associated with the risk for schizophrenia. Our results provide an integrated view of how genetic variants may affect brain structures that lead to distinct disease phenotypes. The method of multi-scale analysis that was described in this research, may help to advance the understanding of the etiology of schizophrenia.
Digital humanities and new directions in South Korea
Authors: Lee Jisu , Lee Hye-Eun
Published: December 2018

The course of reprocessing knowledge and information about social sciences and humanities using digital technology is taking root as a new field of academia called the ‘digital humanities’ (DH). While the social sciences and humanities in South Korea have shown a marked reluctance toward the integration of digital technology, the perception of its necessity as a new methodology for developing these fields in the digital age is growing. Until recently, analytical studies on the status and contents of DH were conducted on data from the western world. Despite their late start, however, Asian countries have begun conducting research on DH with enthusiasm. In order for DH to be properly established in each country, it is essential to set the direction by investigating the pre-requisites for DH studies in that country, as well as the current and future demands. As such, this study discusses the current status and issues regarding DH in South Korea by analyzing the trends of DH research published in South Korea, as well as by examining the status and perception of DH among actual scholars. Based on this study’s findings, we present strategies for improving education programs on DH in South Korea and promulgate the necessity of using DH methodologies in the study of social sciences and humanities to develop global networks and academic communication.
Preliminary Clinical Microneurosurgical Experience With the 4K3-Dimensional Microvideoscope (ORBEYE) System for Microneurological Surgery: Observation Study
Authors: Murai Yasuo , Sato Shun , Yui Kanako , Morimoto Daijiro , Ozeki Tomohiro , Yamaguchi Masahiro , Tateyama Kojiro , Nozaki Toshiki , Tahara Shigeyuki , Yamaguchi Fumio , Morita Akio
Published: December 2018

BACKGROUND

The exoscope has been reported as a novel neurosurgical instrumentation in clinical practice.

OBJECTIVE

To investigate the possibility that ORBEYE (OE), a novel instrument that excludes eyepiece lenses and allows for microsurgery by observation of the 4K3D monitor, could replace microscopes.

METHODS

We report 22 clinical cases by 5 experienced neurosurgeons and the comparative results of training 10 residents. An observation study with questionnaire survey was conducted on usability. Twelve items including image quality, eyestrain, and function of the arm were evaluated.

RESULTS

The following 22 clinical procedures were conducted: surgery for intracranial hemorrhage (n = 2) and brain tumor (n = 8), laminectomy (n = 3), aneurysm clipping (n = 3), vascular anastomosis (n = 2), carotid endarterectomy (n = 2), and nerve decompression (n = 1). No complications were observed. The fluorescent study, including indocyanine-green and 5-aminolevunic acid, allowed for clear depiction on the 4K monitor. The surgeon could operate in a comfortable posture. Similar to the microscope, it was possible to change the optical and viewing axes with the OE, but the OE was switched to the microscope or endoscope in hematoma removal and pituitary surgery. Residents judged that eyestrain was strong (P = .0096). Experienced neurosurgeons acting as assistants judged that the scope arm's range of movement was narrow (P = .0204). Sixty percent of residents judged that the OE was superior to the microscope.

CONCLUSION

Although based on limited experience, it was not possible to substitute the microscope with the OE in all operations; however, the OE surpasses the microscope in terms of ergonomic features.
Technical Aspects and Operative Nuances Using a High-Definition 3-Dimensional Exoscope for Cerebral Bypass Surgery
Authors: Nossek Erez , Schneider Julia R , Kwan Kevin , Kulason Kay O , Du Victor , Chakraborty Shamik , Rahme Ralph , Faltings Lukas , Ellis Jason , Ortiz Rafael , Boockvar John A , Langer David J
Published: December 2018

BACKGROUND

Cerebral bypass operation is a technically challenging operation that requires excellent surgical visibility and efficient ergonomics to minimize complications and maximize successful revascularization. Despite the operative microscope's utilization for the past two generations, there remains a need for continued improvement in operative visualization and surgical ergonomics.

OBJECTIVE

To report the positives and negatives of our initial experience using a novel 4 K high-definition (4K-HD) 3-dimensional (3D) exoscope (EX) for cranial bypass surgery.

METHODS

A retrospective review over 6 mo was performed of all patients who have undergone cerebral bypass surgery at a single institution using the 4K-HD 3D EX. Advantages and disadvantages of the EX and clinical outcome of the patients were assessed.

RESULTS

A total of 5 patients underwent cerebral EC-IC bypass surgery with no EX-related complications and successful revascularization. The lightweight design of the EX allowed for easy instrument maneuverability as well as uncomplicated surgical set up in the operating room. The assistance of the cosurgeon was significantly more efficient compared to that of the operating microscope. The large monitor allowed for an immersive, collaborative, and valuable educational surgical experience.

CONCLUSION

Using the EX for cerebral bypass surgery, with 3D ultra-high-definition optics, enhancements of ergonomics, and improved training, we believe that the 3D 4K-HD EX may represent the next generation of operative scopes in microneurosurgery.
Predicting organizational readiness to implement HIV prevention with couples using practitioners’ intentions: testing a heuristic
Authors: Witte Susan S , Pinto Rogerio , Choi C Jean , Wall Melanie M
Published: December 2018

Couple-based interventions may play a key role in ending the AIDS epidemic. Progress has been made in demonstrating successful implementation of both manual-based and web-based modalities of couple-based HIV prevention in clinical trials. To ensure real world implementation, however, we need a better understanding of how best to prepare organizations to support such interventions. We sought to examine which domains of staff-reported organizational readiness predicted providers’ intention to deliver a couple-based HIV-prevention intervention. Organizational readiness was assessed at baseline from 253 facilitators enrolled in a randomized clinical trial testing dissemination and implementation of a couple-based HIV prevention program (2007–2012). Consistent with current organizational-readiness theory, we measured general capacities; capacities specific to a couple-based intervention; and staff motivation to implement the intervention. We used multilevel regression models to examine the influence of these capacities on intention to implement at 6-, 12-, and 18-month follow-up, adjusting for staff age, education, role, years of service, and randomized condition. Higher perceived organizational resources (B = 0.126, p = .028) and better staff motivation (B = 0.510, p = .009) were significant predictors of increased intention to facilitate Connect. Higher organizational resource availability and stronger motivation to facilitate the intervention are key domains that could inform administrator and staff training to strengthen readiness for couple-based programs. However, further research is needed to clarify the role of these domains regarding actual implementation.
Species of freshwater invertebrates that are sensitive to one saline water are mostly sensitive to another saline water but an exception exists
Authors: Hills Kasey A. , Hyne Ross V. , Kefford Ben J.
Published: December 2018

Coal mining and extraction of methane from coal beds generate effluent with elevated salinity or major ion concentrations. If discharged to freshwater systems, these effluents may have adverse environmental effects. There is a growing body of work on freshwater invertebrates that indicates variation in the proportion of major ions can be more important than salinity when determining toxicity. However, it is not known if saline toxicity in a subset of species is representative of toxicity across all freshwater invertebrates. If patterns derived from a subset of species are representative of all freshwater invertebrates, then we would expect a correlation in the relative sensitivity of these species to multiple saline waters. Here, we determine if there is a correlation between the acute (96 h) lethal toxicity in freshwater invertebrates to synthetic marine salts (SMS) and sodium bicarbonate (NaHCO
3
) added to dechlorinated Sydney tap water. NaHCO
3
is a major component of many coal bed effluents. However, most salinization in Australia exhibits ionic composition similar to seawater, which has very little HCO
3
−
. Across all eight species tested, NaHCO
3
was 2–50 times more toxic than SMS. We also observed strong correlations in the acute toxicity of seven of the tested species to SMS and NaHCO
3
. The strongest relationship (LC50
r
2
= 0.906) was dependent on the exclusion of one species,
Paratya australiensis
(Decopoda: Atyidae), which was the most sensitive species tested to NaHCO
3
, but the second-most tolerant of SMS. We conclude that differences in the toxicity of different proportions of major ions can be similar across a wide range of species. Therefore, a small subset of the invertebrate community can be representative of the whole. However, there are some species, which based on the species tested in the current study appear to be a minority, that respond differently to saline effluent and need to be considered separately. We discuss the implications of this study for the management of saline coal bed waters.

This article is part of the theme issue ‘Salt in freshwaters: causes, ecological consequences and future prospects'.
Structure and assembly of aClostridioides difficilespore polar appendage
Authors: Antunes Wilson , Pereira Fátima C. , Feliciano Carolina , Saujet Laure , Vultos Tiago dos , Couture-Tosi Evelyne , Péchiné Severine , Bruxelle Jean-François , Janoir Claire , Melo Luís V. , Brito Patrícia , Martin-Verstraete Isabelle , Serrano Mónica , Dupuy Bruno , Henriques Adriano O.
Published: December 2018

Clostridioides difficile, a strict anaerobic spore-former, is the main cause of nosocomial disease associated to antibiotic therapy in adults and a growing concern in the community. Spores are the main infectious, persistence and transmission vehicle. Spore germination occurs in the intestine and the resulting vegetative cells will produce the toxins responsible for the disease symptoms, and spores. During sporulation, a wild type population bifurcates into two main spore morphotypes, with or without a thick exosporium. We show that this bifurcation extends to the formation of spores with a robust polar appendage or spores with a short appendage or that lack this structure. The cysteine-rich CdeM protein localizes to the appendage and around the entire surface of the spore, and is a major structural component of the exosporium, which we show is continuous with the appendage. In aCdeMmutant, when present, the polar appendage is short and disorganized. We show that wild type andcdeMspores with a short or no appendage germinate poorly in response to taurocholate, compared to those with an appendage.cdeMspores of the two types, however, germinate faster than their wild type counterparts. Thus, while the absence of CdeM may increase the permeability of spores to taurocholate, proper assembly of the appendage is also important for germination. Consistent with an overall enhancement of germination, acdeMmutant shows increased virulence in a hamster model of disease. For a wild type population, spores with a short or no appendage germinate slower than the appendage-bearing spores. Differences in transmission, persistence and disease severity may result, in part, from their proportion in a spore population.
Dynamic urinary proteomic analysis in a Walker 256 intracerebral tumor model
Authors: Zhang Linpei , Li Yuqiu , Meng Wenshu , Ni Yanying , Gao Youhe
Published: December 2018

Patients with primary and metastatic brain cancer have an extremely poor prognosis, mostly due to the late diagnosis of disease. Urine, which lacks homeostatic mechanisms, is an ideal biomarker source that accumulates early and highly sensitive changes to provides information about the early stage of disease. A rat model mimicking the local tumor growth process in the brain was established with intracerebral Walker 256 (W256) cell injection. Urine samples were collected on days 3, 5 and 8 after injection and then analyzed by LC-MS/MS. In the intracerebral W256 model, no obvious clinical manifestations changes or abnormal MRI signals were found on days 3 and 5; at these time points, nine proteins were changed significantly in the urine of all 8 tumor rats. On day 8, when tumors were detected by MRI, twenty-five differential proteins were identified, including 10 proteins that have been reported to be closely related to tumor metastasis or brain tumors. The differential urinary proteomes were compared with those from the subcutaneous W256 model and the intracerebral C6 model. Few differential proteins overlapped. Specific differential protein patterns were observed among the three models, indicating that the urinary proteome can reflect the difference when tumor cells with different growth characteristics are inoculated into the brain and when identical tumor cells are inoculated into different areas, specifically, the subcutis and the brain.
Exploring different sequence representations and classification methods for the prediction of nucleosome positioning
Authors: Kostagiolas Nikos , Pittaras Nikiforos , Nikolaou Christoforos , Giannakopoulos George
Published: December 2018

Nucleosomes form the first level of DNA compaction and thus bear a critical role in the overall genome organization. At the same time, they modulate chromatin accessibility and, through a dynamic equilibrium with other DNA-binding proteins, may shape gene expression. A number of large-scale nucleosome positioning maps, obtained for various genomes, has compelled the importance of nucleosomes in the regulation of gene expression and has shown constraints in the relative positions of nucleosomes to be much stronger around regulatory elements (i.e. promoters, splice junctions and enhancers). At the same time, the great majority of nucleosome positions appears to be rather flexible. Various computational methods have in the past been used in order to capture the sequence determinants of nucleosome positioning but, as the extent to which DNA sequence preferences may guide nucleosome occupancy largely varies, this has proved to be rather difficult. In order to focus on highly specific sequence attributes, in this work we have analyzed two well-defined sets of nucleosome-occupied sites (NOS) and nucleosome-free-regions (NFR) from the genome of S. cerevisiae, with the use of textual representations. We employed 3 different genomic sequence representations (Hidden Markov Models, Bag-of-Words and N-gram Graphs) combined with a number of machine learning algorithms on the task of classifying genomic sequences as nucleosome-free (NFR) or nucleosome-occupied NOS (to be further amended based on updated results). We found that different approaches that involve the usage of different representations or algorithms can be more or less effective at predicting nucleosome positioning based on the textual data of the underlying genomic sequence. More interestingly, we show that N-gram Graphs, a sequence representation that takes into account both k-mer occurrences and relative positioning at various lengths scales is outperforming other methodologies and may thus be a choice of preference for the analysis of DNA sequences with subtle constraints.