bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydroeconomics
Authors: Pulido-Velazquez Manuel , Tilmant Amaury
Published: January 2022

The management of water resources systems involves influencing and improving the interaction among three subsystems: natural (biophysical), economic, and legal-institutional frameworks. In this sense, hydroeconomic models have the advantage of analyzing water management problems through models that explicitly represent these interactions. The combination of economic, engineering, and environmental aspects of management provides better-informed results for decision making in the complex environment in which water management operates.

Hydroeconomic models (HEMs) are spatially distributed management models of a river basin or system in which both water supply and demands are economically and hydrologically characterized. This definition is sometimes relaxed to refer in general to water resources management models that include the economic component. In HEMs, the management and allocation of water is either driven by the economic value of water or economically assessed, which contributes to policy analysis and reveals opportunities for better economic management. The traditional view of water demand as a fixed requirement to be satisfied is modified by a view of demand that adapts to the changes in the scarcity of water. The integration of economics in HEMs allows the identification of the best combination of water supply and demand management options within a consistent framework. As water scarcity increases worldwide, water managers will increasingly turn to tools that reveal solutions to increase efficiency in water use, fostering improved economic development through better-informed policy choices.
Dualism
Authors: Montero Barbara Gail
Published: January 2022

‘Dualism’ asks: is the mind distinct from the body? Dualism is the theory of mind that answers this question in the affirmative. Looking into Dualism’s ancient origins show us some of the key arguments for dualism. Dualism is thought, by its proponents, to solve one of the great problems in philosophy: the mind‒body problem. Cartesian dualism and René Descartes’s arguments are based on the premise that it is possible to imagine one’s mind existing without one’s body and one’s body without one’s mind. There are also two contemporary arguments for dualism: the knowledge argument, according to which dualism must be true because knowledge of all physical facts does not suffice for understanding conscious experience, and the so-called ‘zombie’ argument according to which the mind must be distinct from the body since a bodily duplicate of a human would not have conscious experiences. Can conceivability be a guide to possibility? In other words, whether one’s ability to imagine a certain situation is reason to believe that such a situation is possible.
Emotions
Authors: Montero Barbara Gail
Published: January 2022

‘Emotions’ asks: how ought we to understand the emotions? There are a number of body-based theories of the emotions, according to which an emotion is an awareness of certain bodily processesWilliam James presents an ‘subtraction argument’, which is the thought experiment which asks us to imagine what is left of an emotion if we subtract the relevant bodily processes from an emotion. Body-based theories can be contrasted with judgement-based theories, which align emotions with judgements. There are also a number of theories of emotions put forward by proponents of the embodied mind thesis, who see the somatic nervous system, which controls voluntary actions such as reaching and walking, as playing a crucial role in emotion.
1. What is geometry?
Authors: Dunajski Maciej
Published: January 2022

‘What is geometry?’ mentions the Greek philosopher Pythagoras of Samos and his followers, the Pythagoreans, who spent their time unveiling the relationship between numbers and geometric forms. They were credited for what is now known as the Pythagorean theorem, wherein for any right-angled triangle the square of the hypotenuse is equal to the sum of the squares of the other two sides. Geometry stands out from most other branches of mathematics, as the proof of a theorem can be given in pictorial terms. The Pythagorean theorem is valid in Euclidean geometry and relies on concepts that play a central role in the theorem.
6. Other geometries
Authors: Dunajski Maciej
Published: January 2022

‘Other geometries’ offers an overview of some modern geometries and their links with other areas of mathematics, such as Gauss lemma in number theory and Gaussian distributions in statistics. The Atiyah–Singer index theorem, proved in 1963 by Michael Atiyah and Isadore Singer, is a celebrated result of geometry in the last 60 years. Felix Klein had the idea of defining geometry as a pair consisting of a space a two-dimensional plane and a group of all affine transformations of the plane. Grigori Perelman’s proof showed the Poincare conjecture, which was formulated in the early 20th century by French mathematician Henri Poincaré.
Changes in Functional and Numerical Responses of the Parasitoid WaspTrichogramma brassicae(Hymenoptera: Trichogrammatidae) Over 45 Generations of Rearing onEphestia kuehniella
Authors: Ghaemmaghami Ehsan , Fathipour Yaghoub , Bagheri Abdoolnabi , Talebi Ali Asghar , Reddy Gadi V P
Published: January 2022

We assessed the functional and numerical responses of Trichogramma brassicae Bezdenko under long-term rearing (45 generations, G5-G45) on eggs of a common factitious host, Ephestia kuehniella Zeller (Lepidoptera: Pyralidae). Under such long-term mass rearing, the function response of this parasitoid shifted from Type III (from G5 to G20) to Type II (from G25 to G45). The maximum attack rate (T/Th) (33.62 hosts/day) and the shortest handling time (0.7138 ± 0.0272 h) were recorded in G5. Also, G45 had the lowest attack rate (21.67 hosts/day) and longest handling time (1.1076 ± 0.0689 h). The handling time increased gradually over the generations (P reg <0.01, R2 = 0.903). The number of eggs laid by the parasitoid increased significantly with increased host density, but reached a plateau at very high densities. While no significant differences in daily parasitism were observed over 45 generations at densities of 2, 4, 8, and 16 available host eggs per wasp, there were significant differences in parasitism at host densities of 32, 64, and 128 eggs per wasp. T. brassicae females were more active and foraged more frequently in earlier generations (G5 to G20), which allowed wasps to parasitize more E. kuehniella eggs compared to later generations. Also, continuous mass rearing of T. brassicae negatively affected foraging behavior and the quality of wasps after G20. However, rejuvenation of the colony by adding field-collected parasitoids or rearing wasps on more suitable factitious hosts is strongly recommended to lower the negative effects of long-term mass rearing on quality of this parasitoid.
Considerations for integrated cognitive behavioural treatment for older adults with coexisting nocturia and insomnia
Authors: Vaughan Camille P , Markland Alayne D , Huang Alison J , Alessi Cathy A , Guzman Andrew , Martin Jennifer L , Bliwise Donald L , Johnson II Theodore M , Burgio Kathryn L , Fung Constance H
Published: January 2022

Nocturia and chronic insomnia disorder are common conditions that frequently coexist in older adults. Existing medication treatments for each condition have risks, particularly in older adults. While treatment guidelines recommend starting with behavioural therapy for each condition, no existing program simultaneously addresses nocturia and insomnia. Existing behavioural interventions for nocturia or insomnia contain concordant and discordant components. An expert panel (including geriatricians with sleep or nocturia research expertise, sleep psychologists and a behavioural psychologist) was convened to combine and reconcile elements of behavioural treatment for each condition. Concordant treatment recommendations involve using situational self-management strategies such as urge suppression or techniques to influence homeostatic drive for sleep. Fluid modification such as avoiding alcohol and evening caffeine and regular self-monitoring through a daily diary is also appropriate for both conditions. The expert panel resolved discordant recommendations by eliminating overnight completion of voiding diaries (which can interfere with sleep) and discouraging routine overnight voiding (a stimulus control strategy). The final product is an integrated cognitive behavioural treatment that is delivered by advanced practice providers weekly over 5 weeks. This integrated program addresses the common scenario of coexisting nocturia and chronic insomnia disorder.
A Guide to Estimating the Reference Range From a Meta-Analysis Using Aggregate or Individual Participant Data
Authors: Siegel Lianne , Murad M Hassan , Riley Richard D , Bazerbachi Fateh , Wang Zhen , Chu Haitao
Published: January 2022

Clinicians frequently must decide whether a patient’s measurement reflects that of a healthy “normal” individual. Thus, the reference range is defined as the interval in which some proportion (frequently 95%) of measurements from a healthy population is expected to fall. One can estimate it from a single study or preferably from a meta-analysis of multiple studies to increase generalizability. This range differs from the confidence interval for the pooled mean and the prediction interval for a new study mean in a meta-analysis, which do not capture natural variation across healthy individuals. Methods for estimating the reference range from a meta-analysis of aggregate data that incorporates both within- and between-study variations were recently proposed. In this guide, we present 3 approaches for estimating the reference range: one frequentist, one Bayesian, and one empirical. Each method can be applied to either aggregate or individual-participant data meta-analysis, with the latter being the gold standard when available. We illustrate the application of these approaches to data from a previously published individual-participant data meta-analysis of studies measuring liver stiffness by transient elastography in healthy individuals between 2006 and 2016.
Four-Day Food Record Macronutrient Intake, With and Without Biomarker Calibration, and Chronic Disease Risk in Postmenopausal Women
Authors: Prentice Ross L , Pettinger Mary , Neuhouser Marian L , Raftery Daniel , Zheng Cheng , Gowda G A Nagana , Huang Ying , Tinker Lesley F , Howard Barbara V , Manson JoAnn E , Wallace Robert , Mossavar-Rahmani Yasmin , Johnson Karen C , Lampe Johanna W
Published: January 2022

We recently evaluated associations of biomarker-calibrated protein intake, protein density, carbohydrate intake, and carbohydrate density with the incidence of cardiovascular disease, cancer, and diabetes among postmenopausal women in the Women’s Health Initiative (1993–present, 40 US clinical centers). The biomarkers relied on serum and urine metabolomics profiles, and biomarker calibration used regression of biomarkers on food frequency questionnaires. Here we develop corresponding calibration equations using food records and dietary recalls. In addition, we use calibrated intakes based on food records in disease association estimation in a cohort subset (n = 29,294) having food records. In this analysis, more biomarker variation was explained by food records than by FFQs for absolute macronutrient intake, with 24-hour recalls being intermediate. However, the percentage of biomarker variation explained was similar for each assessment approach for macronutrient densities. Invasive breast cancer risk was related inversely to carbohydrate and protein densities using food records, in analyses that included (calibrated) total energy intake and body mass index. Corresponding analyses for absolute intakes did not differ from the null, nor did absolute or relative intakes associate significantly with colorectal cancer or coronary heart disease. These analyses do not suggest major advantages for food records or dietary recalls in comparison with less costly and logistically simpler food frequency questionnaires for these nutritional variables.
Blood Pressure Control Among Non-Hispanic Black Adults Is Lower Than Non-Hispanic White Adults Despite Similar Treatment With Antihypertensive Medication: NHANES 2013–2018
Authors: Hayes Donald K , Jackson Sandra L , Li Yanfeng , Wozniak Gregory , Tsipas Stavros , Hong Yuling , Thompson-Paul Angela M , Wall Hilary K , Gillespie Cathleen , Egan Brent M , Ritchey Matthew D , Loustalot Fleetwood
Published: January 2022

BACKGROUND

Controlled blood pressure can prevent or reduce adverse health outcomes. Social and structural determinants may contribute to the disparity that despite equivalent proportions on antihypertensive medication, non-Hispanic Black (Black) adults have lower blood pressure control and more cardiovascular events than non-Hispanic White (White) adults.

METHODS

Data from 2013 to 2018 National Health and Nutrition Examination Survey were pooled to assess control among Black and White adults by antihypertensive medication use and selected characteristics using the 2017 American College of Cardiology/American Heart Association (ACC/AHA) Blood Pressure Guideline definition (systolic blood pressure <130 mm Hg and diastolic blood pressure <80 mm Hg) among 4,739 adults.

RESULTS

Among those treated with antihypertensive medication, an estimated 34.9% of Black and 45.0% of White adults had controlled blood pressure. Control was lower for Black and White adults among most subgroups of age, sex, education, insurance status, usual source of care, and poverty–income ratio. Black adults had higher use of diuretics (28.5%—Black adults vs. 23.5%—White adults) and calcium channel blockers (24.2%—Black adults vs. 14.7%—White adults) compared with White adults. Control among Black adults was lower than White adults across all medication classes including diuretics (36.1%—Black adults vs. 47.3%—White adults), calcium channel blockers (30.2%—Black adults vs. 40.1%—White adults), and number of medication classes used.

CONCLUSIONS

Suboptimal blood pressure control rates and disparities warrant increased efforts to improve control, which could include addressing social and structural determinants along with emphasizing implementation of the 2017 ACC/AHA Blood Pressure Guideline into clinical practice.
Implementation of a pharmacy-led virtual academic detailing program at the US Veterans Health Administration
Authors: Himstreet Julianne E , Shayegani Ramona , Spoutz Patrick , Hoffman Jonathan D , Midboe Amanda M , Hillman Ashley , Marin Jennifer , Chen Andrea , Smith Jason P , Manning Jane M , Almeida Andrea , Gray Caroline P , Erhardt Taryn A , Garcia Carla C , Freeman Blake A , Christopher Melissa L D , Bounthavong Mark
Published: January 2022

Purpose

To provide a summary of the implementation of a virtual academic detailing pilot program at the US Department of Veterans Affairs (VA).

In September 2018, VA Pharmacy Benefits Management implemented a virtual academic detailing (“e-Detailing”) pilot program across 3 regional networks. Academic detailing involves multifaceted collaborative outreach delivered by trained healthcare clinicians to other clinicians using targeted educational interventions that improve clinical decision-making. Across VA, academic detailing programs are primarily staffed by specially trained clinical pharmacist specialists. Implementation began with an in-person meeting to train academic detailers on using the virtual academic detailing platform (VA Video Connect) and virtual soft skills, which was followed by regular facilitation meetings to address issues and share experiences. During e-Detailing program implementation, coronavirus disease 2019 (COVID-19) emerged, prompting the US Department of Health and Human Services to declare a public health emergency. VA followed with restrictions on nonessential travel for all employees, thus hampering in-person academic detailing activities. Fortunately, e-Detailing provided an alternative channel for academic detailers across VA to continue delivering critical outreach to providers during the pandemic. Qualitative assessment of academic detailers’ and providers’ perceptions on e-Detailing highlighted the need for local leadership support for e-Detailing and telehealth, the efficiency of virtual compared to in-person visits, and potential time savings resulting from avoidance of long commutes.

Conclusion

The timing of e-Detailing implementation during the COVID-19 pandemic illustrates the need and potential for a virtual platform to deliver timely provider outreach.
Feeding level is associated with altered liver transcriptome and follicle selection in hen
Authors: Stephens Claire S , Hill-Ricciuti Alexandra , Francoeur Laurie , Johnson Patricia A
Published: January 2022

Genetic selection for particular traits in domestic animals may have altered the optimal feedback regulation among systems regulating appetite, growth, and reproduction. Broiler breeder chickens have been selected for fast and efficient growth and, unless feed restricted, consume excessively resulting in poor reproductive efficiency. We examined the effect of dietary treatment in full-fed and restricted-fed broiler breeder hens on ovarian responses, liver morphology, and transcriptome associated with reproductive function. Although full-fed broiler breeder hens had lower egg production (P < 0.01), the total number of ovarian follicles >8 mm (P < 0.01), 6–8 mm (P < 0.03), and 3–5 mm (P < 0.04) were greater in full-fed hens compared to restricted-fed hens. There was a large amount of lipid accumulation in the liver of full-fed hens and differential gene analysis yielded 120 genes that were differentially expressed >2-fold in response to feeding level (P < 0.01; false discovery rate < 0.05). Elevated T3 may indicate that general metabolism was affected by diet and GHR (P < 0.01) and insulin like growth factor 1 (IGF1) (P < 0.04) mRNA expression were both greater in the liver of full-fed hens as compared to restricted-fed hens. It is likely that selection for increased growth, associated with enhanced activity of the IGF1 system, has altered nutritional coupling of feed intake to follicle development.
Extended-course antibiotic prophylaxis in lower limb amputation: randomized clinical trial
Authors: Souroullas Panayiotis , Barnes Rachel , Carradice Daniel , Smith George , Huang Chao , Chetter Ian
Published: January 2022

Background

Lower limb amputation (LLA) is typically described as ‘clean surgery’, but surgical-site infection (SSI) rates are high and there is significant variation in antibiotic prophylaxis practice. This study aimed to determine whether an extended period of antibiotic prophylaxis (5-day course) is superior to a short course (24 h) in preventing SSI in patients undergoing minor and major LLA.

Methods

Patients undergoing minor and major amputation from a single vascular unit were recruited and randomized to receive either a 5-day or a 24-h prophylactic course of antibiotics. Patients with significant baseline infection were excluded. Outcomes included the incidence of SSI and impaired wound healing (IWH), both measured using ASEPSIS criteria, the need for further surgery, duration of hospital stay, and mortality up to 1 year.

Results

Some 161 patients were recruited to the study, and 152 were included in the analysis. A 5-day course of antibiotics was associated with a lower incidence of SSI (11.8 versus 39.5 per cent; P < 0.001) and lower incidence of IWH (22.4 versus 58 per cent; P < 0.001). Fewer patients receiving the 5-day course required amputation revisional surgery (6.6 versus 21 per cent; P = 0.010). Duration of hospital stay and mortality rates were similar. The presence of SSI (odds ratio (OR) 5.14, 95 per cent c.i. 1.96 to 13.45; P < 0.001) and IWH (OR 4.62, 1.68 to 12.72; P = 0.003) increased the need for revisional surgery. SSI increased the duration of hospital stay: median 28 (i.q.r. 16–40) versus 14 (9–21) days (P = 0.045).

Conclusion

SSI and IWH are common after LLA and have a significant impact on outcome. A 5-day course of antibiotic prophylaxis was associated with a reduction in both SSI and IWH compared with a 24-h course, and this reduced the need for further surgery. Registration number: NCT02018094 (http://www.clinicaltrials.gov); EudraCT 2012-003146-32 (https://www.clinicaltrialsregister.eu).
Betulinic acid accelerates diabetic wound healing by modulating hyperglycemia-induced oxidative stress, inflammation and glucose intolerance
Authors: Xie Weiguo , Hu Weigang , Huang Zhuo , Li Min , Zhang Hongyu , Huang Xiaodong , Yao Paul
Published: January 2022

Background

Diabetes significantly delays wound healing through oxidative stress, inflammation and impaired re-epithelialization that lead to defective regulation of the healing process, although the related mechanism remains unclear. Here, we aim to investigate the potential role and mechanism for the beneficial effect of betulinic acid (BA) on diabetic wound healing.

Methods

The molecular effect of BA on hyperglycemia-mediated gene expression, oxidative stress, inflammation and glucose uptake was evaluated in endothelial, fibroblast and muscle cells. Burn injury was introduced to streptozotocin-induced diabetic rats and BA administration through either an intraperitoneal (IP) or topical (TOP) technique was used for wound treatment. Glucose tolerance was evaluated in both muscle tissue and fibroblasts, while oxidative stress and inflammation were determined in both the circulatory system and in wound tissues. The effect of BA on the wound healing process was also evaluated.

Results

BA treatment reversed hyperglycemia-induced glucose transporter type 4 (GLUT4) suppression in both muscle and fibroblast cells. This treatment also partly reversed hyperglycemia-mediated suppression of endothelial nitric oxide synthase (eNOS), nuclear factor erythroid 2-related factor 2 (Nrf2) signaling and nuclear factor NFκB p65 subunit (NFκB p65) activation in endothelial cells. An in vivo rat study showed that BA administration ameliorated diabetes-mediated glucose intolerance and partly attenuated diabetes-mediated oxidative stress and inflammation in both the circulatory system and wound tissues. BA administration by both IP and TOP techniques significantly accelerated diabetic wound healing, while BA administration by either IP or TOP methods alone had a significantly lower effect.

Conclusions

BA treatment ameliorates hyperglycemia-mediated glucose intolerance, endothelial dysfunction, oxidative stress and inflammation. Administration of BA by both IP and TOP techniques was found to significantly accelerate diabetic wound healing, indicating that BA could be a potential therapeutic candidate for diabetic wound healing.
Kinetics of immune responses to SARS-CoV-2 proteins in individuals with varying severity of infection and following a single dose of the AZD1222
Authors: Jayathilaka Deshni , Jeewandara Chandima , Gomes Laksiri , Jayadas Tibutius Thanesh Pramanayagam , Kamaladasa Achala , Somathilake Gayasha , Guruge Dinuka , Pushpakumara Pradeep Darshana , Ranasinghe Thushali , Aberathna Inoka Sepali , Danasekara Saubhagya , Gunathilaka Buddini , Kuruppu Heshan , Wijewickrama Ananda , Wijayamuni Ruwan , Schimanski Lisa , Tan T K , Ogg Graham S , Townsend Alain , Malavige Gathsaurie Neelika
Published: January 2022

To characterize the IgG and IgA responses to different SARS-CoV-2 proteins, we investigated the antibody responses to SARS-CoV-2 following natural infection and following a single dose of AZD1222 (Covishield), in Sri Lankan individuals. The IgG and IgA responses were assessed to S1, S2, RBD, and N proteins in patients at 4 weeks and 12 weeks since the onset of illness or following vaccination. Antibodies to the receptor-binding domain of SARS-CoV-2 wild type (WT), α, β, and λ and ACE2 (Angiotensin Converting Enzyme 2) receptor blocking antibodies were also assessed in these cohorts. For those with mild illness and in vaccines, the IgG responses to S1, S2, RBD, and N protein increased from 4 weeks to 12 weeks, while it remained unchanged in those with moderate/severe illness. In the vaccines, IgG antibodies to the S2 subunit had the highest significant rise (P < 0.0001). Vaccines had several-fold lower IgA antibodies to all the SARS-CoV-2 proteins tested than those with natural infection. At 12 weeks, the haemagglutination test (HAT) titres were significantly lower to the α in vaccines and significantly lower in those with mild illness and in vaccines to β and for λ. No such difference was seen in those with moderate/severe illness. Vaccines had significantly less IgA to SARS-CoV-2, but comparable IgG responses those with natural infection. However, following a single dose vaccines had reduced antibody levels to the VOCs, which further declined with time, suggesting the need to reduce the gap between the two doses, in countries experiencing outbreaks due to VOCs.
Effects of DRD2/ANKK1 and COMT Val158Met polymorphisms on stabilization against and adaptation to unexpected events
Authors: Trempler Ima , Binder Ellen , Reuter Martin , Plieger Thomas , Standke Isabel , Mecklenbrauck Falko , Meinert Susanne , Forstner Andreas J , Nöthen Markus M , Rietschel Marcella , Stürmer Sophie , Dannlowski Udo , Tittgemeyer Marc , Lencer Rebekka , Fink Gereon R , Schubotz Ricarda I
Published: January 2022

Genetic variations affecting dopaminergic neuromodulation such as the DRD2/ANKK1 and the COMT Val158Met polymorphisms contribute to goal-directed behavior that requires a balance between stabilization and updating of current states and behaviors. Dopamine is also thought to be relevant for encoding of surprise signals to sensory input and adaptive learning. A link between goal-directed behavior and learning from surprise is therefore plausible. In the present fMRI study, we investigated whether DRD2 and COMT polymorphisms are related to behavioral responses and neural signals in the caudate nucleus and dlPFC during updating or stabilizing internal models of predictable digit sequences. To-be-detected switches between sequences and to-be-ignored digit omissions within a sequence varied by information-theoretic quantities of surprise and entropy. We found that A1 noncarriers and Val-carriers showed a lower response threshold along with increased caudate and dlPFC activation to surprising switches compared with A1-carriers and Met-homozygotes, whose dlPFC activity increased with decreasing switch surprise. In contrast, there were overall smaller differences in behavioral and neural modulation by drift surprise. Our results suggest that the impact of dopamine-relevant polymorphisms in the flexibility-stability trade-off may result in part from the role of dopamine in encoding the weight afforded to events requiring updating or stabilization.
Corticocortical innervation subtypes of layer 5 intratelencephalic cells in the murine secondary motor cortex
Authors: Im Sanghun , Ueta Yoshifumi , Otsuka Takeshi , Morishima Mieko , Youssef Mohammed , Hirai Yasuharu , Kobayashi Kenta , Kaneko Ryosuke , Morita Kenji , Kawaguchi Yasuo
Published: January 2022

Feedback projections from the secondary motor cortex (M2) to the primary motor and sensory cortices are essential for behavior selection and sensory perception. Intratelencephalic (IT) cells in layer 5 (L5) contribute feedback projections to diverse cortical areas. Here we show that L5 IT cells participating in feedback connections to layer 1 (L1) exhibit distinct projection patterns, genetic profiles, and electrophysiological properties relative to other L5 IT cells. An analysis of the MouseLight database found that L5 IT cells preferentially targeting L1 project broadly to more cortical regions, including the perirhinal and auditory cortices, and innervate a larger volume of striatum than the other L5 IT cells. We found experimentally that in upper L5 (L5a), ER81 (ETV1) was found more often in L1-preferring IT cells, and in IT cells projecting to perirhinal/auditory regions than those projecting to primary motor or somatosensory regions. The perirhinal region-projecting L5a IT cells were synaptically connected to each other and displayed lower input resistance than contra-M2 projecting IT cells including L1-preferring and nonpreferring cells. Our findings suggest that M2-L5a IT L1-preferring cells exhibit stronger ER81 expression and broader cortical/striatal projection fields than do cells that do not preferentially target L1.
Clinical Decision Support Systems to Reduce Unnecessary Clostridioides difficile Testing Across Multiple Hospitals
Authors: Rock Clare , Abosi Oluchi , Bleasdale Susan , Colligan Erin , Diekema Daniel J , Dullabh Prashila , Gurses Ayse P , Heaney-Huls Krysta , Jacob Jesse T , Kandiah Sheetal , Lama Sonam , Leekha Surbhi , Mayer Jeanmarie , Mena Lora Alfredo J , Morgan Daniel J , Osei Patience , Pau Sara , Salinas Jorge L , Spivak Emily , Wenzler Eric , Cosgrove Sara E
Published: January 2022

Background

Inappropriate Clostridioides difficile testing has adverse consequences for patients, hospitals, and public health. Computerized clinical decision support (CCDS) systems in the electronic health record (EHR) may reduce C. difficile test ordering; however, effectiveness of different approaches, ease of use, and best fit into healthcare providers’ (HCP) workflow are not well understood.

Methods

Nine academic and 6 community hospitals in the United States participated in this 2-year cohort study. CCDS (hard stop or soft stop) triggered when a duplicate C. difficile test order was attempted or if laxatives were recently received. The primary outcome was the difference in testing rates pre– and post–CCDS interventions, using incidence rate ratios (IRRs) and mixed-effect Poisson regression models. We performed qualitative evaluation (contextual inquiry, interviews, focus groups) based on a human factors model. We identified themes using a codebook with primary nodes and subnodes.

Results

In 9 hospitals implementing hard-stop CCDS and 4 hospitals implementing soft-stop CCDS, C. difficile testing incidence rate (IR) reduction was 33% (95% confidence interval [CI]: 30%–36%) and 23% (95% CI: 21%–25%), respectively. Two hospitals implemented a non-EHR-based human intervention with IR reduction of 21% (95% CI: 15%–28%). HCPs reported generally favorable experiences and highlighted time efficiencies such as inclusion of the patient’s most recent laxative administration on the CCDS. Organizational factors, including hierarchical cultures and communication between HCPs caring for the same patient, impact CCDS acceptance and integration.

Conclusions

CCDS systems reduced unnecessary C. difficile testing and were perceived positively by HCPs when integrated into their workflow and when displaying relevant patient-specific information needed for decision making.
Natural Areas of Cerrado Foster Wasp (Hymenoptera) Diversity in Human Modified Landscapes
Authors: Simplício Viviane dos Santos , Abot Alfredo Raúl , Shimbori Eduardo Mitio , Garcia Flávio Roberto Mello , Carolina Onody Helena , Castro Torres Lucas , Zazycki Luiza Cristiane Fialho , de Souza Marcos Magalhaes , Rodrigues Marciel Elio
Published: January 2022

Land use changes from native vegetation to agriculture, livestock grazing, and urban development are among the main problems related to biodiversity loss worldwide. In this paper we evaluate how land use changes (eucalypt plantation and pasture) affect the richness and assemblage of wasps (Braconidae, Ichneumonidae, Pompilidae, and Vespidae), in comparison with nearby areas with native vegetation in the Cerrado. Specimens were collected at six points, with two Malaise traps at each location. The collections were performed monthly for 10 d, for 12 mo. A total of 773 hymenopterans of the selected groups were collected, representing 253 species or morphospecies. Richness of the families Ichneumonidae and Pompilidae between the areas did not present significant differences. For the families Braconidae and Vespidae, the richness was greater in the eucalypt plantation and pasture areas compared to the native area. Species composition in the native habitat was different from either of the managed habitats in the studied environment. Furthermore, the composition of wasps in native areas varied less throughout the sampling campaigns when compared with the pasture and eucalyptus sites. In native areas, 85 exclusive morphospecies were found. Thus, changes in land use may cause changes in the composition of wasp species, since areas with native vegetation presented more heterogeneous and stable environments than the other land uses. The maintenance of native areas, even if close to planted forest and/or pasture areas, could be the best way to combine forest productivity with biodiversity conservation.
The Heterogeneous Tax Pass-Through Under Different Vertical Relationships
Authors: Bajo-Buenestado Raúl , Borrella-Mas Miguel Ángel
Published: January 2022

A large body of literature has examined the impact of the horizontal market structure on the tax incidence on consumers. However, the extent to which the vertical market structure affects the tax pass-through—which might be particularly relevant in the presence of the double marginalisation problem—is an unexplored question. Using a confidential dataset of gas station contracts with a major Spanish refiner, in combination with their retail fuel prices and characteristics, we document that the pass-through of a tax on prices is about 38% higher in vertically integrated gas stations than in independent ones. Our estimates allow us to assess the impact on government revenue and emissions under different counterfactual market scenarios.
New resources for the Drosophila 4th chromosome: FRT101F enabled mitotic clones and Bloom syndrome helicase enabled meiotic recombination
Authors: Goldsmith Samuel L , Shimell MaryJane , Tauscher Petra , Daly Samantha M , Shimmi Osamu , O’Connor Michael B , Newfeld Stuart J
Published: January 2022

Genes on the long arm of the Drosophila melanogaster 4th chromosome are difficult to study because the chromosome lacks mitotic and meiotic recombination. Without recombination numerous standard methods of genetic analysis are impossible. Here, we report new resources for the 4th. For mitotic recombination, we generated a chromosome with an FRT very near the centromere in 101F and a derivative that carries FRT101F with a distal ubiquitously expressed GAL80 transgene. This pair of chromosomes enables both unmarked and MARCM clones. For meiotic recombination, we demonstrate that a Bloom syndrome helicase and recombination defective double mutant genotype can create recombinant 4th chromosomes via female meiosis. All strains will be available to the community via the Bloomington Drosophila Stock Center. Additional resources for studies of the 4th are in preparation and will also be made available. The goal of the 4th Chromosome Resource Project is to accelerate the genetic analysis of protein-coding genes on the 4th, including the 44 genes with no demonstrated function. Studies of these previously inaccessible but largely conserved genes will close longstanding gaps in our knowledge of metazoan development and physiology.
The Community as the Unit of Healing: Conceptualizing Social Determinants of Health and Well-Being for Older American Indian Adults
Authors: Jaramillo Elise T , Haozous Emily , Willging Cathleen E
Published: January 2022

Background and Objectives

Multiple racial and social inequities shape health and access to health care for American Indian Elders, who have a lower life expectancy than all other aging populations in the United States. This qualitative study examines how upstream social determinants of health influence Elders’ ability to access and use health care.

Research Design and Methods

Between June 2016 and March 2017, we conducted individual, semistructured interviews with 96 American Indian Elders, aged 55 and older, and 47 professionals involved in planning or delivering care to Elders in 2 states in the U.S. Southwest. Transcripts were analyzed iteratively using grounded theory approaches, including open and focused coding. A group of American Indian Elders and allies called the Seasons of Care Community Action Board guided interpretation and prioritization of findings.

Results

Participants described multiple barriers that hindered Elders’ ability to access health care services and providers, which were largely tied to funding shortages and bureaucratic complexities associated with health care and insurance systems. Where available, community resources bridged service gaps and helped Elders navigate systems.

Discussion and Implications

Longstanding structural inequities for American Indians manifest in barriers to health equity, many of which are situated at the community level. These are compounded by additional disparities affecting older adults, rural residents, and marginalized citizens in general. Findings underscore the importance of health and policy initiatives for American Indian Elders that emphasize the community as the focus of intervention.
Comparative analysis of common alignment tools for single-cell RNA sequencing
Authors: Brüning Ralf Schulze , Tombor Lukas , Schulz Marcel H , Dimmeler Stefanie , John David
Published: January 2022

Background

With the rise of single-cell RNA sequencing new bioinformatic tools have been developed to handle specific demands, such as quantifying unique molecular identifiers and correcting cell barcodes. Here, we benchmarked several datasets with the most common alignment tools for single-cell RNA sequencing data. We evaluated differences in the whitelisting, gene quantification, overall performance, and potential variations in clustering or detection of differentially expressed genes. We compared the tools Cell Ranger version 6, STARsolo, Kallisto, Alevin, and Alevin-fry on 3 published datasets for human and mouse, sequenced with different versions of the 10X sequencing protocol.

Results

Striking differences were observed in the overall runtime of the mappers. Besides that, Kallisto and Alevin showed variances in the number of valid cells and detected genes per cell. Kallisto reported the highest number of cells; however, we observed an overrepresentation of cells with low gene content and unknown cell type. Conversely, Alevin rarely reported such low-content cells. Further variations were detected in the set of expressed genes. While STARsolo, Cell Ranger 6, Alevin-fry, and Alevin produced similar gene sets, Kallisto detected additional genes from the Vmn and Olfr gene family, which are likely mapping artefacts. We also observed differences in the mitochondrial content of the resulting cells when comparing a prefiltered annotation set to the full annotation set that includes pseudogenes and other biotypes.

Conclusion

Overall, this study provides a detailed comparison of common single-cell RNA sequencing mappers and shows their specific properties on 10X Genomics data.
Explicitly sexing health security: analysing the downstream effects of Panama’s sex-segregated COVID-19 disease control policy
Authors: Wenham Clare , Arauz-Reyes Nelva Marissa , Meneses-Sala Daniela , Rueda-Borrero Corina
Published: January 2022

In response to COVID-19, Panama implemented a sex-segregated lockdown policy whereby women were allowed to access essential services on Monday, Wednesday and Friday and men on Tuesday, Thursday and Saturday. The logic was to reduce disease transmission by controlling population circulation at any one time. We sought to understand the impact of this policy approach on Panamanian society. To do so, we undertook key informant interviews with representatives from groups of society that have been significantly affected by this policy across Panamanian society. Framework analysis was undertaken on interview transcripts to identify key trends, which were latterly triangulated with academic, media and grey literature. Firstly, we engage with intersectional analyses to show that those most affected were marginalised groups including trans population, disabled groups, indigenous groups and migrants who faced discrimination as a consequence of this policy. Secondly, we highlight practical tensions that individuals faced relating to access to resources (financial, health-related and beyond), and third we interrogate the methods used to enforce this policy, and the role of the police and exemption passes. We conclude that this policy was regressive in that it affected those most vulnerable in Panamanian society, entrenching existing inequalities. Before implementing sex-segregated policies in future health crises, governments must seek advice of gender and equality advisors and ensure impact assessments are undertaken to understand the burden such policies may pose across society.
TNFRSF10A downregulation induces retinal pigment epithelium degeneration during the pathogenesis of age-related macular degeneration and central serous chorioretinopathy
Authors: Mori Kenichiro , Ishikawa Keijiro , Fukuda Yosuke , Ji Rui , Wada Iori , Kubo Yuki , Akiyama Masato , Notomi Shoji , Murakami Yusuke , Nakao Shintaro , Arakawa Satoshi , Shiose Satomi , Hisatomi Toshio , Yoshida Shigeo , Kannan Ram , Sonoda Koh-Hei
Published: January 2022

Age-related macular degeneration (AMD) and central serous chorioretinopathy (CSC) are common diseases that can cause vision loss in older and younger populations. These diseases share pathophysiological conditions derived from retinal pigment epithelium (RPE) dysfunction. Tumor necrosis factor receptor superfamily 10A (TNFRSF10A)-LOC389641 with the same lead single-nucleotide polymorphism (SNP) (rs13278062) is the only overlapped susceptibility locus found in both AMD and CSC through genome-wide association studies. This lead SNP has been reported to alter the transcriptional activity of TNFRSF10A. This study aimed to elucidate the function of TNFRSF10A in RPE degeneration using human primary RPE cells and Tnfrsf10 knockout (Tnfrsf10−/−) mice. TNFRSF10A was found to be localized in human RPE. In vitro assays revealed that a T allele of rs13278062, the risk allele for AMD and CSC, downregulated TNFRSF10A transcription in RPE, leading to decreased cell viability and increased apoptosis through protein kinase C-α (PKCA) downregulation. Treatment with phorbol 12-myristate 13-acetate, a PKC activator, rescued the cell viability. Morphological RPE abnormality was found in the retina of Tnfrsf10−/− mice. Our data suggest that downregulation of TNFRSF10A expression inactivates PKCA signaling and causes cellular vulnerability of the RPE, which may contribute to the pathogenesis of AMD and CSC.
On Schrödinger Groups of Fractional Powers of Hermite Operators
Authors: Bui The Anh , Duong Xuan Thinh , Hong Qing , Hu Guorong
Published: January 2022

Let $\mathcal {H}=-\Delta + |x|^2$ be the Hermite operator on $\mathbb R^n$ with $n\ge 2$. In this paper, we prove the boundedness of Schrödinger groups of fractional powers of $\mathcal {H}$ on Lebesgue and Hardy spaces. More precisely, we prove that (a) for $p \in (1,\infty )$, $\gamma>0$ and $\beta /\gamma \geq n|1/p -1/2|$, $$ \begin{align*} \big\|\mathcal{H}^{-\beta /2}e^{it \mathcal{H}^{\gamma /2}}f\big\|_{L^p(\mathbb R^n)} \leq C (1 + |t|)^{n|1/p-1/2|}\|f\|_{L^p(\mathbb R^n)}, \quad \forall t \in \mathbb{R}, \end{align*}$$and (b) for $p \in (0, 1]$, $\gamma>0$ and $\beta /\gamma \geq n(1/p -1/2)$, $$ \begin{align*} \big\|\mathcal{H}^{-\beta /2}e^{it \mathcal{H}^{\gamma /2}}f\big\|_{H^p_{\mathcal{H}}(\mathbb R^n)} \leq C (1 + |t|)^{n(1/p-1/2)}\|f\|_{H^p_{\mathcal{H}}(\mathbb R^n)}, \quad \forall t \in \mathbb{R}, \end{align*}$$where $H^p_{\mathcal {H}}(\mathbb R^n)$ is the Hardy space associated with the operator $\mathcal {H}$. These estimates improve related result of Thangavelu [22] and have some interesting applications.
Generalized Affine Springer Theory and Hilbert Schemes on Planar Curves
Authors: Garner Niklas , Kivinen Oscar
Published: January 2022

We show that Hilbert schemes of planar curve singularities and their parabolic variants can be interpreted as certain generalized affine Springer fibers for $GL_n$, as defined by Goresky–Kottwitz–MacPherson. Using a generalization of affine Springer theory for Braverman–Finkelberg–Nakajima’s Coulomb branch algebras, we construct a rational Cherednik algebra action on the homology of the Hilbert schemes and compute it in examples. Along the way, we generalize to the parahoric setting the recent construction of Hilburn–Kamnitzer–Weekes, which may be of independent interest. In the spherical case, we make our computations explicit through a new general localization formula for Coulomb branches. Via results of Hogancamp–Mellit, we also show the rational Cherednik algebra acts on the HOMFLY-PT homologies of torus knots. This work was inspired in part by a construction in 3D ${\mathcal {N}}=4$ gauge theory.
Lassa Virus Replicon Particle Vaccine Protects Strain 13/N Guinea Pigs Against Challenge With Geographically and Genetically Diverse Viral Strains
Authors: Spengler Jessica R , Kainulainen Markus H , Welch Stephen R , Coleman-McCray JoAnn D , Harmon Jessica R , Condrey Jillian A , Scholte Florine E M , Nichol Stuart T , Montgomery Joel M , Albariño César G , Spiropoulou Christina F
Published: January 2022

Lassa virus (LASV) causes mild to severe hemorrhagic fever disease in humans. Strain 13/N guinea pigs are highly susceptible to infection with LASV strain Josiah (clade IV), providing a critical model system for therapeutics and vaccine development. To develop additional models of disease, we detail the clinical course in guinea pigs infected with 5 geographically and genetically diverse LASV strains. Two of the developed models (LASV clades II and III) were then used to evaluate efficacy of a virus replicon particle vaccine against heterologous LASV challenge, demonstrating complete protection against clinical disease after a single vaccination dose.
Cancer-derived cholesterol sulfate is a key mediator to prevent tumor infiltration by effector T cells
Authors: Tatsuguchi Takaaki , Uruno Takehito , Sugiura Yuki , Sakata Daiji , Izumi Yoshihiro , Sakurai Tetsuya , Hattori Yuko , Oki Eiji , Kubota Naoto , Nishimoto Koshiro , Oyama Masafumi , Kunimura Kazufumi , Ohki Takuto , Bamba Takeshi , Tahara Hideaki , Sakamoto Michiie , Nakamura Masafumi , Suematsu Makoto , Fukui Yoshinori
Published: January 2022

Effective tumor immunotherapy requires physical contact of T cells with cancer cells. However, tumors often constitute a specialized microenvironment that excludes T cells from the vicinity of cancer cells, and its underlying mechanisms are still poorly understood. DOCK2 is a Rac activator critical for migration and activation of lymphocytes. We herein show that cancer-derived cholesterol sulfate (CS), a lipid product of the sulfotransferase SULT2B1b, acts as a DOCK2 inhibitor and prevents tumor infiltration by effector T cells. Using clinical samples, we found that CS was abundantly produced in certain types of human cancers such as colon cancers. Functionally, CS-producing cancer cells exhibited resistance to cancer-specific T-cell transfer and immune checkpoint blockade. Although SULT2B1b is known to sulfate oxysterols and inactivate their tumor-promoting activity, the expression levels of cholesterol hydroxylases, which mediate oxysterol production, are low in SULT2B1b-expressing cancers. Therefore, SULT2B1b inhibition could be a therapeutic strategy to disrupt tumor immune evasion in oxysterol-non-producing cancers. Thus, our findings define a previously unknown mechanism for tumor immune evasion and provide a novel insight into the development of effective immunotherapies.