bluuebunny/crossref_metadata_2025 huggingface dataset:
Rationale for and Design of the Study of Early Enteral Dextrose in Sepsis: A Pilot Placebo‐Controlled Randomized Clinical Trial
Authors: Shah Faraaz Ali , Kitsios Georgios D. , Zhang Yingze , Morris Alison , Yende Sachin , Huang David T. , O'Donnell Christopher P. , McVerry Bryan J.
Published: May 2019

Background

Sepsis is characterized by life‐threatening organ dysfunction caused by a dysregulated host response to infection and affects over 1 million Americans annually. Loss of glycemic control in sepsis is associated with increased morbidity and mortality, and novel approaches are needed to promote euglycemia and improve outcomes in sepsis. Recent studies from our laboratory demonstrate that early low‐level enteral dextrose infusion in septic mice attenuates the systemic inflammatory response and improves glycemic control by inducing intestine‐derived incretin hormone secretion.

Aim

The aim of the Study of Early Enteral Dextrose in Sepsis (SEEDS) is to test the effect of a 24‐hour enteral dextrose infusion in critically ill septic patients as a therapeutic agent to decrease systemic inflammation and promote euglycemia.

Methods

SEEDS is a single‐center, double‐blind, randomized, controlled trial that will enroll 60 septic patients admitted to the intensive care units at the University of Pittsburgh Medical Center Health System in Pittsburgh. Participants will be randomized 1:1 to receive enteral dextrose (n = 30) or water (placebo, n = 30) infusion for 24 hours. The primary outcome is the circulating interleukin‐6 level measured after the 24‐hour infusion compared between dextrose and placebo groups. Secondary outcomes include postinfusion circulating insulin, incretin, and other proinflammatory cytokine levels, as well as incidence of hyperglycemia and hypoglycemia during the infusion period.

Discussion

This trial will characterize the effects of early enteral dextrose on endogenous endocrine pathways and the systemic inflammatory response in sepsis. The results of this trial will inform future larger interventional studies of early enteral nutrients in critically ill patients with sepsis.
Dexmedetomidine prescribing in Australian intensive care units: an observational study
Authors: O'Brien Daniel W. , Cotta Menino O. , Choo Lyn , Fowler Stephen , Downey Maria , Fisquet Stephanie , Tan Ivy , Roberts Jason A.
Published: May 2019

Dexmedetomidine is used in the intensive care unit (ICU) as a short‐term sedative. The data included in the manufacturer's product information is controversial, and there is little consensus to guide initial dosing and titration. This observational study surveyed the practice of dexmedetomidine use in Australian ICUs. An expression of interest (EOI) for a multisite observational study was sent to members of the ICU email group of the Society of Hospital Pharmacists Australia (SHPA). Participating members collected treatment‐related data for patients meeting inclusion criteria between January 2013 and July 2014. Six of 14 sites that responded positively to the EOI returned complete datasets, and 232 patients met the inclusion criteria. The main reported indications for dexmedetomidine use across the six sites were to manage agitation (33.2%), to aid extubation (32.8%) and to sedate (34.0%). The median duration of therapy was 42 h (range 1–672 h). Only nine patients (3.9%) received loading doses. The median maximum dose used for maintenance therapy in patients ranged from 1.2 to 4.0 microgram/kg per h. There was a significant disparity of practice across sites, as evidenced by differences in reported indication, off‐label use, rates of loading doses and doses used for maintenance therapy. Consensus prescribing guidelines are required to guide more consistent and evidence‐based prescribing of dexmedetomidine.
Seasonal flooding effects on deer in the Mississippi river batture
Authors: Jones Phillip D. , Strickland Bronson K. , Demarais Stephen , McKinley William T. , Ernst James R. , Klassen Jessica. A.
Published: May 2019

Effective deer management requires managers to distinguish between the density‐dependent influence of harvest and local environmental factors. The Batture region of the Lower Mississippi River Valley comprises land adjacent to the river that is not protected by the levee system, and is therefore subject to seasonal flooding with potential to influence the morphology and demographics of white‐tailed deer (Odocoileus virginianus). Using harvest records of 42,954 females and 3,588 males from 61 Batture properties in Mississippi and Louisiana, we created linear regression models of deer body development and recruitment indices to compare the influence of seasonal flooding, harvest rate, growing season weather, and agronomic forage availability during 1988–2016. Overall, deer in the Batture appeared to be more influenced by extrinsic factors than by harvest. Seasonal flooding appeared in every model and generally had stronger effects than weather or harvest variables. Flooding from 1 to 2 years prior, regardless of season, was correlated with greater female body mass, lactation rates, and antler mass of trophy males, possibly reflecting silt deposition effects on soil fertility and promotion of new understory forages. Conversely, current‐year flooding effects were invariably negative, implying direct effects of displacement. Summer flooding was concentrated during late gestation and peak parturition periods, and exhibited the potential to reduce fall lactation rates by 18%. Harvest rates correlated negatively with female body mass and had no correlation with lactation or antler mass. We detected contrasting long‐term trends of decreasing body mass and increasing harvest rate that may reflect deteriorating habitat. Similar to flooding, increased temperatures and rainfall had negative effects for the current year, whereas increased temperatures had positive effects when occurring in the previous year. Surprisingly, annual variation in the amount of soybeans planted appeared in one model only, exhibiting a small positive effect on antler mass. We hypothesize that extensive planting of soybeans in levee‐protected lands just outside the Batture maintained substantial soybean availability despite variation in the amount planted. Given the dominating influence of flooding and weather on deer physical and reproductive parameters in the Batture, these extrinsic variables should be incorporated into the interpretation of harvest data. The common practice of curtailing harvest, particularly female harvest, following years with extensive flooding is likely counterproductive unless intensive flooding occurs during summer. © 2019 The Wildlife Society.
Lower Critical Solution Temperature in Poly(N‐Isopropylacrylamide): Comparison of Detection Methods and Molar Mass Distribution Influence
Authors: García‐Peñas Alberto , Biswas Chandra Sekhar , Liang Weijun , Wang Yu , Stadler Florian J.
Published: May 2019

Poly(N‐Isopropylacrylamide) has a broad potential range of biomedical applications owing to its lower critical solution temperature (LCST). This work tries to elucidate the real influence of several parameters on LCST by comparing homopolymers prepared by free radical polymerization and reversible addition–fragmentation chain transfer (RAFT) polymerization using conventional calorimetry, turbidimetry, and rheology as well as how three different methods can be used to detect the LCST. These methods are compared to gain a deeper understanding of the underlying processes and how they are related to molar mass and synthesis methods. The diverse interactions associated with the LCST transitions are more sensitive depending on the ratio defined between polymerization degrees and end‐group effects. Thus, the selection of a high sensitive method for LCST detection depends on the molecular features defined from the homopolymer. In addition, this work shows also the importance of the RAFT agent selected for the synthesis, which can modify substantially the LCST in comparison with other methods reported where the use of chemicals, complex processes, and costs considerably increase.
Optimization of b‐value schemes for estimation of the diffusion coefficient and the perfusion fraction with segmented intravoxel incoherent motion model fitting
Authors: Jalnefjord Oscar , Montelius Mikael , Starck Göran , Ljungberg Maria
Published: May 2019

Purpose

Intravoxel incoherent motion (IVIM) modeling for estimation of the diffusion coefficient (D) and perfusion fraction (f) is increasingly popular, but no consensus on standard protocols exists. This study provides a framework for optimization of b‐value schemes for reduced estimation uncertainty of D and f from segmented model fitting.

Theory

Analytical expressions for uncertainties of D and f from segmented model fitting were derived as Cramer‐Rao lower bounds (CRLBs).

Methods

Optimized b‐value schemes were obtained for 3 to 12 acquisitions and in the limit of infinitely many acquisitions through constrained minimization of the CRLBs, with b‐values constrained to be 0 or 200 to 800 s/mm2. The optimized b‐value scheme with eight acquisitions was compared with b‐values linearly distributed in the allowed range using simulations and in vivo liver data from seven healthy volunteers.

Results

All optimized b‐value schemes contained exactly three unique b‐values regardless of the total number of acquisitions (0, 200, and 800 s/mm2) with repeated acquisitions distributed approximately as 1:2:2. Compared with linearly distributed b‐values, the variability of estimates of D and f was reduced by approximately 30% as seen both in simulations and in repeated in vivo measurements.

Conclusion

The uncertainty of IVIM D and f estimates can be reduced by the use of optimized b‐value schemes.
Methods of identifying delirium: A research protocol
Authors: Mulkey Malissa A. , Hardin Sonya R. , Munro Cindy L. , Everhart D. Erik , Kim S. , Schoemann Alexander M. , Olson DaiWai M.
Published: May 2019

Delirium is an acute disorder affecting up to 80% of intensive care unit (ICU) patients. It is associated with a 10‐fold increase in cognitive impairment, triples the rate of in‐hospital mortality, and costs $164 billion annually. Delirium acutely affects attention and global cognitive function with fluctuating symptoms caused by underlying organic etiologies. Early detection is crucial because the longer a patient experiences delirium the worse it becomes and the harder it is to treat. Currently, identification is through intermittent clinical assessment using standardized tools, like the Confusion Assessment Method for ICU. Such tools work well in clinical research but do not translate well into clinical practice because they are subjective, intermittent and have low sensitivity. As such, healthcare providers using these tools fail to recognize delirium symptoms as much as 80% of the time. Delirium‐related biochemical derangement leads to electrical changes in electroencephalographic (EEG) patterns followed by behavioral signs and symptoms. However, continuous EEG monitoring is not feasible due to cost and need for skilled interpretation. Studies using limited‐lead EEG show large differences between patients with and without delirium while discriminating delirium from other causes. The Ceribell is a limited‐lead device that analyzes EEG. If it is capable of detecting delirium, it would provide an objective physiological monitor to identify delirium before symptom onset. This pilot study was designed to explore relationships between Ceribell and delirium status. Completion of this study will provide a foundation for further research regarding delirium status using the Ceribell data.
Fabrication of electrospun keratin nanofiber membranes for air and water treatment
Authors: Figoli Alberto , Ursino Claudia , Sanchez Ramirez Diego Omar , Carletto Riccardo Andrea , Tonetti Cinzia , Varesano Alessio , De Santo Maria Penelope , Cassano Alfredo , Vineis Claudia
Published: May 2019

Keratin proteins extracted from wool fibers by sulfitolysis were electrospun for the production of active nanofiber membranes (NFMs). The keratin NFMs were composited with nylon woven fabric for improving their mechanical properties as a filtration material. The prepared membranes were characterized in terms of morphology, pore size, contact angle, and performance of water and air permeability. Experimental data showed that most of investigated parameters were affected by the electrospinning time: that is, roughness rose by increasing the electrospinning time, while the narrowest pore size distribution was obtained at the longest electrospinning time (2 h). The pure water permeability (PWP) was greater for the produced NFMs than for the commercial microfiltration membranes and decreased by increasing the electrospinning time. At the longest electrospinning time, the produced NFMs showed a PWP of about 45.7 m3/m2 h bar, which is a value greater than those obtained by conventional materials used in water filtration, including microfiltration membranes. According to the data of contact angle measurements, the high hydrophobicity of NFMs membranes could reinforce their stability in water. Other potential applications could be venting, adsorption of VOCs, and separation of oils from oil/water emulsions. POLYM. ENG. SCI., 59:1472–1478 2019. © 2019 Society of Plastics Engineers
In‐Depth Proteomics Analysis to Identify Biomarkers of Papillary Thyroid Cancer Patients Older Than 45 Years with Different Degrees of Lymph Node Metastases
Authors: Zhan Shaohua , Wang Tianxiao , Wang Meng , Li Jinming , Ge Wei
Published: May 2019

Purpose

Investigations of the molecular mechanisms underlying the metastatic phenotype of papillary thyroid cancer (PTC) and identification of novel candidate biomarkers to better predict PTC metastasis are urgently required.

Experimental Design

Tandem mass tag‐based quantitative proteomics approach is used to identify differentially expressed proteins (DEPs) in PTC tumorous tissues with different degrees of lymph node metastases (LNMs). Furthermore, DEPs and their clinical significance are analyzed in another independent Cancer Genome Atlas dataset.

Results

The protein profiles among tumorous tissues with different degrees of LNMs are clearly distinguished, while the protein profiles in normal tissues are remarkably similar. DEPs in tumorous tissues are mostly enriched in the categories associated with pathological hallmarks of cancer, including extracellular matrix, metabolism, and cell growth. The expression patterns of six DEPs (LAMC2, LAMB3, ATP5A1, MYO1G, S100A4, and FAS) are confirmed by the Cancer Genome Atlas dataset. Additionally, the elevated expression of LAMC2 and MYO1G mRNA levels in tumorous tissues show a positive relationship with unfavorable variables, including larger tumor size, LNMs, high AJCC staging, BRAFV600E mutation, and poor prognosis.

Conclusions and Clinical Relevance

LAMC2 and MYO1G are identified as potential candidate biomarkers for the prediction of PTC metastasis and prognosis.
Long‐term cardiovascular effects of vandetanib and pazopanib in normotensive rats
Authors: Cooper Samantha L. , Carter Joanne J. , March Julie , Woolard Jeanette
Published: May 2019

Vandetanib and pazopanib are clinically available, multi‐targeted inhibitors of vascular endothelial growth factor (VEGF) and platelet‐derived growth factor (PDGF) receptor tyrosine kinases. Short‐term VEGF receptor inhibition is associated with hypertension in 15%‐60% of patients, which may limit the use of these anticancer therapies over the longer term. To evaluate the longer‐term cardiovascular implications of treatment, we investigated the “on”‐treatment (21 days) and “off”‐treatment (10 days) effects following daily administration of vandetanib, pazopanib, or vehicle, in conscious rats. Cardiovascular variables were monitored in unrestrained Sprague‐Dawley rats instrumented with radiotelemetric devices. In Study 1, rats were randomly assigned to receive either daily intraperitoneal injections of vehicle (volume 0.5 mL; n = 5) or vandetanib 25 mg/kg/day (volume 0.5 mL; n = 6). In Study 2, rats received either vehicle (volume 0.5 mL; n = 4) or pazopanib 30 mg/kg/day (volume 0.5 mL; n = 7), dosed once every 24 hours for 21 days. All solutions were in 2% Tween, 5% propylene glycol in 0.9% saline solution. Vandetanib caused sustained increases in mean arterial pressure (MAP), systolic blood pressure (SBP), and diastolic blood pressure (DBP) compared to baseline and vehicle. Vandetanib also significantly altered the circadian cycling of MAP, SBP, and DBP. Elevations in SBP were detectable 162 hours after the last dose of vandetanib. Pazopanib also caused increases in MAP, SBP, and DBP. However, compared to vandetanib, these increases were of slower onset and a smaller magnitude. These data suggest that the cardiovascular consequences of vandetanib and pazopanib treatment are sustained, even after prolonged cessation of drug treatment.
Farmer perception of fall armyworm (Spodoptera frugiderda J.E. Smith) and farm‐level management practices in Zambia
Authors: Kansiime Monica K , Mugambi Idah , Rwomushana Ivan , Nunda Winnie , Lamontagne‐Godwin Julien , Rware Harrison , Phiri Noah A , Chipabika Gilson , Ndlovu Mathias , Day Roger
Published: May 2019

BACKGROUND

This paper documents farmer perceptions and management practices for fall armyworm (Spodoptera frugiderda J.E. Smith), providing a baseline for the development of sustainable pest management strategies.

RESULTS

91% of farmers correctly identified fall armyworm, and reported it as the most important maize pest during 2016/2017 cropping season, affecting nearly half of cultivated area. Estimated maize yield loss during the season, attributed to fall armyworm was 28%. A majority of farmers (60%) used pesticides for fall armyworm control, along with other cultural/physical practices – hand picking and crushing egg masses/caterpillars (36%), and application of ash/sand in the funnel (19%). Farmers used various pesticide active ingredients, and protective measures were inadequate; >50% of farmers did not use any protective measures while spraying. Significantly more male than female farmers used pesticides (P = 0.05), and the reverse was true for cultural practices. Significant maize yield differences (P = 0.001) were observed by gender, attributed to differences in utilization of production inputs/practices. At least 77% of farmers received and shared agricultural advice, which can be optimized to spread information on fall armyworm management options.

CONCLUSION

Increased use of pesticides to manage fall armyworm poses health and environmental risks, besides the high cost for farmers and governments. Research into cultural and indigenous practices used by farmers will offer opportunities for alternative and sustainable management practices. Research efforts should pay attention to gender differences in access to resources and inputs. Tackling fall armyworm at the farm level, and averting yield losses will require integrated messaging addressing other production risks. © 2019 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Assimilation of SMOS brightness temperatures in the ECMWF Integrated Forecasting System
Authors: Muñoz‐Sabater J. , Lawrence H. , Albergel C. , Rosnay P. , Isaksen L. , Mecklenburg S. , Kerr Y. , Drusch M.
Published: May 2019

The assimilation of Soil Moisture and Ocean Salinity (SMOS) brightness temperature (TB) data in numerical weather prediction systems influences the state of the soil, which in turn affects the exchange of energy and water fluxes between the soil and the near‐surface atmosphere, with potential implications for the prediction of atmospheric variables. In this paper, the impact of assimilating SMOS TB alone or in combination with screen‐level observations and Advanced Scatterometer (ASCAT) soil moisture retrievals is assessed. Independent quality controlled insitu soil moisture observations belonging to several networks included in the International Soil Moisture Network, were used to validate the quality of both the new soil moisture analyses and the skill to predict soil moisture up to 5 days ahead. The impact on atmospheric variables is indirect and was evaluated through computation of the forecast skill at different lead times. The analysis period was selected to be around the boreal summer, a period of the year when evaporatranspiration fluxes are stronger, and when it is therefore expected that the assimilation of remote‐sensing data provides the largest impact on the state of the soil. The results show that the soil moisture state benefits from the direct assimilation of SMOS TB, especially in better representing the temporal variations of soil moisture. The skill of atmospheric variables is mainly driven by the screen‐level observations. Despite the clear benefits to the soil state, remote‐sensing data need to be used with screen‐level variables to add value to the state of the atmosphere, pointing to inconsistencies in the physical coupling between the land and near‐surface components of the ECMWF Earth system.
Mitigation of cold‐water thermal pollution downstream of a large dam with the use of a novel thermal curtain
Authors: Gray Rachel , Jones Hugh A. , Hitchcock James N. , Hardwick Lorraine , Pepper Darice , Lugg Allan , Seymour Justin R. , Mitrovic Simon M.
Published: May 2019

Hypolimnial releases from dams during periods of thermal stratification modify the downstream riverine thermal regime by decreasing water temperature and reducing natural diel thermal variability. This cold‐water thermal pollution in rivers can persist for hundreds of kilometres downstream of dams and impact important ecological processes such as fish spawning. To mitigate this problem, a first‐of‐its‐kind thermal curtain was fitted to the large bottom release Burrendong Dam on the Macquarie River, Australia. The thermal curtain acts by directing warmer, near‐surface epilimnial water to the low‐level hypolimnial offtake. This study aimed to test the efficacy of the thermal curtain by measuring temperatures before and after the curtains installation, quantifying the magnitude and extent of cold‐water thermal pollution along the Macquarie River downstream of Burrendong Dam. Epilimnial releases with use of the curtain increased diel temperature ranges and the mean monthly water temperature below the dam. Epilimnial releases with use of the curtain increased diel temperature ranges from 0.9°C to 2.5°C and reduced the difference between the mean monthly water temperature of an upstream control and a downstream site by up to 3.5°C. A comparison of the monthly temperature means along the river, indicated that thermal recovery, whereby temperatures returned to within the natural range of upstream temperatures occurred 45 km downstream of the dam during summer when the thermal curtain was deployed, compared with approximately 200 km prior to deployment of the curtain. Our study suggests that the use of thermal curtains can reduce cold‐water thermal pollution and improve ecological outcomes for river ecosystems downstream of dams.
Investigating the turbulent flow characteristics in an open channel with staggered vegetation patches
Authors: Ghani Usman , Anjum Naveed , Pasha Ghufran Ahmed , Ahmad Muhammad
Published: May 2019

In the present study, flow around circular and staggered vegetation patches was investigated numerically. For turbulence modelling, the Reynolds‐averaged Navier–Stokes technique and Reynolds stress model were adopted. The numerical model was validated with the experimental data using varying vegetation density and flow velocities. The simulated results of mean stream‐wise velocities were in close agreement with the experimental results. The results show that the mean stream‐wise velocity in the downstream regions of vegetation patches were reduced, whereas the velocity in the free stream regions were increased. The influence of neighbouring and staggered vegetation patches on the flow was observed. The vegetation patches with larger nondimensional flow blockage (aD = 2.3, where a is the frontal area per volume of patches, and D is the diameter of vegetation patches) offered more turbulence when compared to the patches with a smaller flow blockage (aD = 1.2). Larger turbulence in the form of kinetic energy and turbulent intensity was recorded within the vegetation as well as the regions directly behind the patches. Negative Reynolds stresses were observed at the top of submerged vegetation. The turbulence characteristics peaked at the top of vegetation, that is, z/h = 1.0 (where z is the flow depth, and h is the vegetation height), which may be migrated vertically as the frontal area of the vegetation patch is increased. This high frontal area also increased stream‐wise velocity above the vegetation, leading to an increased variation in turbulence around the vegetation canopy.
Nanoscopic Stoichiometry and Single‐Molecule Counting
Authors: Nino Daniel , Djayakarsana Daniel , Milstein Joshua N.
Published: May 2019

Single‐molecule localization microscopy (SMLM) has the potential to revolutionize proteomic and genomic analyses by providing information on the number and stoichiometry of proteins or nucleic acids aggregating at spatial scales below the diffraction limit of light. Here, a method for molecular counting is presented with SMLM built upon the exponentially distributed blinking statistics of photoswitchable fluorophores, with a focus on organic dyes. A guide to performing this newly developed technique is provided, highlighting many of the challenges and pitfalls, by benchmarking the method on fluorescently labeled, surface mounted DNA origami grids. The accuracy of the results illustrates SMLM's utility for optical “‐omics” analysis.
A method for designing minimum‐cost multisource multisink network layouts
Authors: Heijnen Petra W. , Chappin Emile J.L. , Herder Paulien M.
Published: May 2019

Systems engineers are equipped to design complex networked systems such as infrastructures. A key goal is cost minimization over a vast solution space. However, finding a minimum‐cost system while comprehensively satisfying different stakeholders is challenging and lacks proper methodological support. Stakeholders often employ their own expert estimations for lack of suitable decision‐support methods. In these settings, systems engineers typically require mid‐fidelity, easy‐to‐use methods. We present a rigorous method that quickly finds minimum‐cost solutions for networks with multiple sources and sinks, focusing on pipeline topology, length, and capacity. It can serve as a discussion tool in multiactor design processes, to demarcate the design space, indicate sources of uncertainty, and provoke further analyses, different designs, or contractual negotiations. It is applicable to a wide variety of cases, including many prominent infrastructures needed to mitigate CO₂. We prove that the optimal layout is a minimum‐cost Gilbert tree, and develop a heuristic based on the Gilbert‐Melzak method. We demonstrate the method's efficacy for a case set regarding solution quality, computational time, and scalability. We also show its efficiency and usefulness for systems engineers in real‐world settings. Systems engineers can use the generated cost‐optimal system designs to benchmark any design changes in real‐world negotiation processes.
Pichia pastoris protease‐deficient and auxotrophic strains generated by a novel, user‐friendly vector toolbox for gene deletion
Authors: Ahmad Mudassar , Winkler Christine M. , Kolmbauer Markus , Pichler Harald , Schwab Helmut , Emmerstorfer‐Augustin Anita
Published: May 2019

Targeted gene knockouts play an important role in the study of gene function. For the generation of knockouts in the industrially important yeast Pichia pastoris, several protocols have been published to date. Nevertheless, creating a targeted knockout in P. pastoris still is a time‐consuming process, as the existing protocols are labour intensive and/or prone to accumulate nucleotide mutations. In this study, we introduce a novel, user‐friendly vector‐based system for the generation of targeted knockouts in P. pastoris. Upon confirming the successful knockout, respective selection markers can easily be recycled. Excision of the marker is mediated by Flippase (Flp) recombinase and occurs at high frequency (≥95%). We validated our knockout system by deleting 20 (confirmed and putative) protease genes and five genes involved in biosynthetic pathways. For the first time, we describe gene deletions of PRO3 and PHA2 in P. pastoris, genes involved in proline, and phenylalanine biosynthesis, respectively. Unexpectedly, knockout strains of PHA2 did not display the anticipated auxotrophy for phenylalanine but rather showed a bradytroph phenotype on minimal medium hinting at an alternative but less efficient pathway for production of phenylalanine exists in P. pastoris. Overall, all knockout vectors can easily be adapted to the gene of interest and strain background by efficient exchange of target homology regions and selection markers in single cloning steps. Average knockout efficiencies for all 25 genes were shown to be 40%, which is comparably high.
CP violation in $$ {\overline{B}}^0\to {D}^{\ast +}{\mu}^{-}{\overline{\nu}}_{\mu } $$
Authors: Bhattacharya Bhubanjyoti , Datta Alakabha , Kamali Saeed , London David
Published: May 2019

Abstract

In order to explain the observed anomalies in the measurements of

$$ {R}_{D^{\left(\ast \right)}} $$

R

D

∗

and R

J/ψ
, a variety of new-physics (NP) models that contribute to

$$ b\to c{\tau}^{-}\overline{\nu} $$

b
→
c

τ
−

ν
¯

have been proposed. In this paper, we show how CP-violating observables can be used to distinguish these NP models. Because

$$ {\overrightarrow{p}}_{\tau } $$

p
→

τ

cannot be measured (the decay products of the τ include the undetected ν

τ
), obtaining the angular distribution of

$$ {\overline{B}}^0\to {D}^{\ast +}{\tau}^{-}{\overline{\nu}}_{\tau } $$

B
¯

0

→

D

∗
+

τ
−

ν
¯

τ

is problematic. Instead, we focus here on

$$ {\overline{B}}^0\to {D}^{\ast +}\left(\to {D}^0{\pi}^{+}\right){\mu}^{-}{\overline{\nu}}_{\mu } $$

B
¯

0

→

D

∗
+

→

D
0

π
+

μ
−

ν
¯

μ

. This process may also receive contributions from the same NP, and LHCb intends to measure the CP-violating angular asymmetries in this decay. There are two classes of NP models that contribute to

$$ b\to c{\mu}^{-}{\overline{\nu}}_{{}_{\mu }} $$

b
→
c

μ
−

ν
¯

μ

. These involve (i) a W
′ (two types) or (ii) a leptoquark (LQ) (six types). The most popular NP models predict no CP-violating effects, so the measurement of nonzero CP-violating asymmetries would rule them out. Furthermore these measurements allow one to distinguish the W
′ and LQ models, and to differentiate among several LQ models.
Correction to: Reducing external costs of nitrogen pollution by relocation of pig production between regions in the European Union
Authors: van Grinsven Hans J. M. , van Dam Jan D. , Lesschen Jan Peter , Timmers Marloes H. G. , Velthof Gerard L. , Lassaletta Luis
Published: May 2019

The article Reducing external costs of nitrogen pollution by relocation of pig production between regions in the European Union, written by Hans J. M. van Grinsven, Jan D. van Dam, Jan Peter Lesschen, Marloes H. G. Timmers, Gerard L. Velthof, Luis Lassaletta, was originally published electronically.
Numerical and experimental characterisation of an aeronautic Pitot probe
Authors: Jäckel R. , Gutiérrez Urueta G.L. , Tapia Rodríguez F. , Monreal Jiménez C.
Published: May 2019

Aeronautic Pitot probes (PPs) are extremely important for airspeed and altitude measurements in aviation. Failure of the instrument due to clogging caused by ice formation can lead to dangerous situations. In this work, a commercial aeronautic PP was characterised experimentally regarding its inner composition, material properties and its thermal performance in a climatic wind tunnel. Performance runs were taken out in order to analyse the thermal response of the PP under various operating conditions with a particular emphasis on the cooling process in the case of a heating element failure. Data for the thermal conductivity, diffusivity and specific heat for each material forming the PP were obtained. A numerical model to simulate the thermal behaviour of the PP was created using Comsol Multiphysics (CM). Experimental data were compared with their numerical counterparts for model validation purposes. After the model was validated, the operation of the PP in flight conditions was simulated. The failure of the conventional heating system was analysed to obtain the time until the PP reaches a tip temperature where ice formation can be expected. The tip temperature undercut the zero degrees Celsius mark 165 seconds after the heating element was switched off. The data collected in this work can be used to implement and validate mathematical models in order to predict the thermal performance of Pitot probes in flight conditions.
East African HIV care: depression and HIV outcomes
Authors: Meffert S. M. , Neylan T. C. , McCulloch C. E. , Maganga L. , Adamu Y. , Kiweewa F. , Maswai J. , Owuoth J. , Polyak C. S. , Ake J. A. , Valcour V. G.
Published: May 2019

Importance.

Depression is a common co-morbidity for people living with HIV (PLWH) and is associated with elevated plasma HIV RNA levels. While depression correlates with deficits in antiretroviral (ARV) adherence, little data exist to inform the relationship between depression and HIV vial load more broadly.

Objective.

To examine the relationship between depression and viral load in the African Cohort Study (AFRICOS) independently of ARV adherence.

Design.

PLWH in Kenya, Uganda and Tanzania underwent screening for depression using the Center for Epidemiologic Studies Depression Scale (CESD) upon enrollment at AFRICOS HIV care sites.

Setting.

AFRICOS is an ongoing prospective longitudinal cohort study enrolling HIV-infected adults at HIV care centers including sites in Kenya, Tanzania and Uganda. These sites are administered by President's Emergency Plan For AIDS Relief programs.

Participants.

HIV+ individuals were eligible if they were at least 18 years old, receiving HIV care at the enrolling clinic and consented to data and specimen collection.

Main outcome measure.

CESD.

Results.

Among 2307 participants, 18–25% met the CESD threshold for depression. Depression was associated with decreased ARV adherence (OR 0.59,p =  0.01). Higher scores on three CESD items were significantly associated with 209–282% higher viral load, independently of ARV adherence among participants on ARVs ⩾6 months.

Conclusions.

PLWH had high prevalence of depression on the CESD. Diverse depression symptoms were independently associated with increases in viral load, underscoring the need for comprehensive treatment of depression.
The Mythology of International Rule-of-Law Promotion
Authors: Chalmers Shane
Published: May 2019

In 1992 Peter Fitzpatrick published The Mythology of Modern Law, a work that exposed the constitutive relation between Europe’s racialized imperialism and its conception of modern law. In the three decades since, a renewed field of “law and development” has grown, this time in the name of “the rule of law.” This Article shows how the mythology of modern law endures in this field of rule-of-law development. To do this, Part I draws out the main threads from Mythology. These are then woven through the Article, beginning with the World Justice Project’s Rule of Law Index®, before turning to the United Nations’ rule-of-law assistance, and ending with the World Bank’s 2017 World Development Report. The analysis shows how the mythology of modern law, in its racialized imperial form, is integral to the work of international rule-of-law promotion. One consequence is the denial of “local” law by a rule of law that obtains its authority by purporting to be responsive to legal pluralism. But the Article also points to the mythological possibilities of decolonization, specifically the possibilities of a “mythological legal pluralism” that is attentive to the ways in which the world’s plurality of laws already rule.
Heat Transfer to Slender Bodies at a Mach Number of 5.2
Authors: Fancett R. K.
Published: May 2019

Because of the lack of reliable data on heat transfer to long bodies, measurements have been made to cone-cylinder-flares at a Mach number of 5·2. Axial heat transfer distributions were closely predicted by a modified reference enthalpy method for both laminar and turbulent flows at zero incidence and the heat transfer to the flare windward generator at incidence agreed with laminar theory.
The Interaction of the Wake from an Oscillating Blade with a Fixed Cascade
Authors: Whitehead D. S. , Nabar V. G.
Published: May 2019

The paper presents a theoretical investigation of the flow when the wake from a single vibrating aerofoil interacts with a fixed downstream cascade set normal to the mean flow direction. It is concluded that the effects of the cascade extend upstream by a distance of about one quarter of the wavelength of the fluctuations in the wake. It is also found that the wake passes through the cascade unchanged in strength, but that the cascade sheds vorticity of equal and opposite magnitude, so that, if an average is taken in the direction parallel to the cascade, the wake is annulled.
A Lifting-Surface Theory for the Rectangular Wing in Non-Stationary Flow
Authors: Graham J. M. R.
Published: May 2019

A method of obtaining the load distribution on thin rectangular wings in non-stationary incompressible flow is presented, with particular reference to the problem of gust-induced loading. The method utilises solutions to a Fourier transform of the downwash integral equation, enabling the problem to be expressed in the form of a set of dual integral equations having a series solution. Some values of the overall lift coefficient are computed and compared with values of lift coefficient obtained by collocation methods. The method is easily extendable to subsonic compressible flows.
Stability Derivatives of Sharp Wedges in Viscous Hypersonic Flow
Authors: Hui W. H. , East R. A.
Published: May 2019

Using a perturbation method, the formulae for the pitching stability derivatives of sharp wedges at zero incidence in viscous hypersonic flow are obtained in closed form. The results include the effect of unsteady reflected waves from the bow shock and may be applied to any wedge provided that the bow shock is attached. The effect of viscosity of the gas is included in two parts: first, it thickens the wedge, thus introducing the concept of an effective wedge, thicker than the original wedge by a semi-vertex angle equal to the average inclination of the displacement boundary layer; secondly, it makes this effective wedge deformable. Comparison with previous theories is given.
Numerical Calculations of the Hypersonic Viscid–Inviscid Flow Inside Simple Ducts of Circular Cross-Section
Authors: Lee B. H. K.
Published: May 2019

The method of characteristics and an implicit finite-difference scheme are used to investigate the interaction between the internal flow field and laminar boundary layer in ducts of circular cross-section under the conditions of high Mach number and low Reynolds number. The displacement thickness is added on to the body to form a new “effective body shape” which is used to re-calculate the inviscid flow. Iterations are performed and a solution is obtained when the surface pressures in two consecutive iterations converge to within a specified tolerance. The calculated surface pressures on a 10 degree conical duct placed in a hypersonic stream at M∞=8·34, Re∞=7·5 × 106 and M∞=10·4, Re∞=4·625 × 106 with γ=1·4 show good agreement with experiments. The results are computed for constant wall temperature, using a value of Tw/Tstag=0·23, and the Prandtl number is assumed to be constant and equal to 0·7 throughout the calculations. The type of shock-wave interaction near the axis of symmetry is determined and the computation terminates after the fluid properties behind the reflected shock have been calculated.
Gust Loading on a Thin Aerofoil
Authors: Mugridge B. D.
Published: May 2019

A closed-form expression is derived which gives an approximate solution to the lift generated on a two-dimensional thin aerofoil in incompressible flow with a normal velocity component of the form exp [i(ωt–xx+yy)]. The inaccuracy of the solution when compared with other published work is compensated by the simplicity of the final expression, particularly if the result is required for the calculation of the sound power radiated by an aerofoil in a turbulent flow.
Pressure Distributions and Forces on Rectangular and D-shaped Cylinders
Authors: Bostock B R , Mair W A
Published: May 2019

Measurements in two-dimensional flow on rectangular cylinders confirm earlier work of Nakaguchi et al in showing a maximum drag coefficient when the height h of the section (normal to the stream) is about 1.5 times the width d. Reattachment on the sides of the cylinder occurs only for h/d < 0.35.

For cylinders of D-shaped section (Fig 1) the pressure distribution on the curved surface and the drag are considerably affected by the state of the boundary layer at separation, as for a circular cylinder. The lift is positive when the separation is turbulent and negative when it is laminar. It is found that simple empirical expressions for base pressure or drag, based on known values for the constituent half-bodies, are in general not satisfactory.
Making Offenders Vote: Democratic Expressivism and Compulsory Criminal Voting
Authors: POAMA ANDREI , THEUNS TOM
Published: May 2019

Is criminal disenfranchisement compatible with a democratic political order? This article considers this question in light of a recently developed view that criminal disenfranchisement is justified because it expresses our commitment to democratic values. We call this view expressive disenfranchisement and refer to the general conception in which it is grounded as democratic expressivism. Contra supporters of expressive disenfranchisement, we argue that democratic expressivism does not offer a sound justification of criminal disenfranchisement. Additionally, we argue that, insofar as one really cares about answering serious criminal wrongs via an expression of democratic values, criminal disenfranchisement should be abandoned and replaced with a policy that temporarily obliges the relevant criminals to vote. Democratic expressivists should, in other words, move from supporting the disenfranchisement of serious offenders to endorsing a policy of compulsory criminal voting for a finite period of time.
Religious Orientations of H. G. Wells: a Case Study in Scientific Humanism
Authors: Glover Willis B.
Published: May 2019

The literary career of H. G. Wells began in the reign of Victoria and extended beyond World War II. For some three decades down into the 1930's his ideas on the human situation and the probable future of mankind were as much a part of the popular mind as those of anyone else writing in English. In the last decade of his life, however, there was a sharp decline of interest in Wells which brought him to almost total eclipse by his death in 1946. He had reflected important facets of the mind of an age, and that age had passed. Even at the height of his fame, as we can see clearly now, he was not in the first rank of literary figures and was much less sensitive to what was happening in the West than Eliot or Conrad or even Aldous Huxley.
Preaching and Publication — Chronology and the Style of Thomas Hooker's Sermons
Authors: Herget Winfried
Published: May 2019

In 1630 Thomas Hooker left England to avoid further prosecution by Archbishop Laud. Before him lay an uncertain future, first in Holland, and then, after 1633, in America; behind him, years of increasing recognition as one of the most effective Puritan preachers, especially while he was a lecturer at Chelmsford in Essex. Yet by 1630 only two of Hooker's works had been published: The Poore Doubting Christian Drawne Unto Christ, and the “Epistle to the Reader” in John Rogers' The Doctrine of Faith. Both appeared in 1629.
The Old Phoenician Inscription from Spain Dedicated to Hurrian Astarte
Authors: Cross Frank Moore
Published: May 2019

In 1963 a bronze statuette was acquired by the Museo Arqueológico de Sevilla. It portrays a naked goddess with a modified Ḥatḥor hair style. She is seated, her feet resting on a pedestal which is inscribed with five lines of old Phoenician writing. The writing surface on the pedestal measures only 4.1 × 2.8 cm. and unhappily is marred by bronze disease, that is, by corrosion which swells and flakes. The figurine with its inscription was published by J. M. Solá-Solé in 1966 in an excellent paper which correctly dated the inscription (and the statuette) in the first half of the eighth century B.C. and went far in deciphering the difficult text. In figure 1 we have attempted to draw a facsimile of the statue pedestal based on the published photographs.
The Peoples of Palestine in the Middle Bronze I Period
Authors: Dever William G.
Published: May 2019

The Middle Bronze I period,ca. 2150–1900 B.C., has been regarded until recently as something of a “Dark Age” in the history of Palestine. That this period has yielded so slowly and stubbornly to the probings of the archaeologist now appears to have been due to its basic character: it represents a largely non-urban, transitional culture which (taken together with “EB IV”) spans the interlude of several centuries between the great urban eras of the Early Bronze and the Middle Bronze Ages. Semi-nomads and transitory settlers leave frustratingly few traces for the archaeologist. Nevertheless, intensive research in recent years enables us finally to draw a provisional picture of the material culture of MB I in Palestine (see the sketch in Section B).
The Original Text of CD 7:9–8:2 = 19:5–14
Authors: Murphy-O'Connor Jerome
Published: May 2019

Ideally, textual criticism should precede literary criticism, because the objectivity of the latter is compromised if variants are selected on the basis of their contribution to the literary analysis. In some instances, however, a rigid separation of the two disciplines defeats its own purpose. The Damascus Document (CD) provides a case in point. To date the application of purely textual criticism to 7:9–8:2 = 19:5–14 has yielded no satisfactory and generally accepted solution. In this study I hope to show that the recognition of one paragraph as a secondary insertion simplifies the textual problem to the point where it can be resolved by a simple and plausible hypothesis. The distinction of different levels in a text is one of the many analogies between literary criticism and archaeology, and to this extent makes this contribution an appropriate one in a volume designed to honour the memory of Paul Lapp.
The Money Supply, Economic Management and the Gilt-Edged Market
Authors: Pepper G. T.
Published: May 2019

We unfortunately have a system under which Exchequer financing can, and does, lead to the creation of money quasi-automatically to the extent that the requirements of the Exchequer are not met by genuine savings or taxation. This is the outcome of a financing system perfected in two world wars, when the dangers inherent in the creation of money obviously took second place to other considerations. The utilization of this system in peace-time clearly calls for the utmost restraint.

The Earl of Cromer as Governor of the Bank of England in a speech on 18 May 1966.

The subject of the money supply suddenly became most topical in the Autumn of 1968. It is of importance to investment, in general because of possible changes in the economic management of the United Kingdom, and in particular because of the possible implications for the gilt-edged market.