bluuebunny/crossref_metadata_2025 huggingface dataset:
Agglomeration
Authors: Mori Tomoya
Published: October 2020

Agglomeration of economic activities is the phenomenon that has been observed since humans shifted from migratory life to sedentary life after the spread of farming. Urban agglomerations continue today, and the economy of developed countries is typically dominated by cities. Naturally, agglomeration has been one of the major research topics in urban and regional economics. The formal modeling of agglomeration started in 1970s and grew rapidly thereafter. It first focused on the endogenous city formation; in particular, the formation of the central business district within a city, the presence of which has been treated as exogenous in the classical urban economics. The formation of multiple cities and the agglomeration of more general economic activities as well as their spatial coordination were studied in more recent years. Given the economic integration that took place in different parts of the world in the 1990s and thereafter, today agglomeration has become a common keyword in characterizing not only urban and regional economy, but also international economy.
Balancing Rights and Interests: Reconstructing the Asymmetry Thesis
Authors: Klatt Matthias
Published: October 2020

Dworkin, Schauer and others have argued that the last step of the proportionality test, ie balancing, is subject to a significant asymmetry. While we could balance interests against each other, we could not do so with rights, lest we destroy the unique normative status of rights. If this asymmetry exists, the applicability of balancing would be considerably limited. I analyse the asymmetry thesis and discuss its merits and weaknesses. I then demonstrate how we can accommodate the rationale behind the asymmetry thesis within the principles theory’s account of balancing. My article confirms that proportionality adjudication includes the balancing of rights and interests.
Possession and Damages for Tortious Interferences with Chattels
Authors: Rostill Luke
Published: October 2020

The common law has long maintained that, where a defendant has tortiously interfered with a chattel that was in the claimant’s possession at the time of the wrong, the claimant is, in general, to be presumed to be the ‘absolute and complete owner’ of the chattel. It is argued in this article that the rule lacks a satisfactory justificatory basis: the justification that has been endorsed by the courts is fatally flawed, and the main alternative justifications that have been advanced in the academic literature are also unsatisfactory. If an adequate foundation cannot be found, the rule should be abolished and, if it were to be abolished, there are, it is suggested, good reasons to introduce a similar, but importantly different, rule of presumption.
Labor in the Boardroom
Authors: Jäger Simon , Schoefer Benjamin , Heining Jörg
Published: October 2020

We estimate the wage effects of shared governance, or codetermination, in the form of a mandate of one-third of corporate board seats going to worker representatives. We study a reform in Germany that abruptly abolished this mandate for stock corporations incorporated after August 1994, while it locked the mandate for the slightly older cohorts. Our research design compares firm cohorts incorporated before the reform and after; in a robustness check we draw on the analogous difference in unaffected firm types (LLCs). We find no effects of board-level codetermination on wages and the wage structure, even in firms with particularly flexible wages. The degree of rent sharing and the labor share are also unaffected. We reject that disinvestment could have offset wage effects through the canonical hold-up channel, as shared governance, if anything, increases capital formation.
Deep phenotyping of synovial molecular signatures by integrative systems analysis in rheumatoid arthritis
Authors: Jung Seung Min , Park Kyung-Su , Kim Ki-Jo
Published: October 2020

Objective

RA encompasses a complex, heterogeneous and dynamic group of diseases arising from molecular and cellular perturbations of synovial tissues. The aim of this study was to decipher this complexity using an integrative systems approach and provide novel insights for designing stratified treatments.

Methods

An RNA sequencing dataset of synovial tissues from 152 RA patients and 28 normal controls was imported and subjected to filtration of differentially expressed genes, functional enrichment and network analysis, non-negative matrix factorization, and key driver analysis. A naïve Bayes classifier was applied to the independent datasets to investigate the factors associated with treatment outcome.

Results

A matrix of 1241 upregulated differentially expressed genes from RA samples was classified into three subtypes (C1–C3) with distinct molecular and cellular signatures. C3 with prominent immune cells and proinflammatory signatures had a stronger association with the presence of ACPA and showed a better therapeutic response than C1 and C2, which were enriched with neutrophil and fibroblast signatures, respectively. C2 was more occupied by synovial fibroblasts of destructive phenotype and carried highly expressed key effector molecules of invasion and osteoclastogenesis. CXCR2, JAK3, FYN and LYN were identified as key driver genes in C1 and C3. HDAC, JUN, NFKB1, TNF and TP53 were key regulators modulating fibroblast aggressiveness in C2.

Conclusions

Deep phenotyping of synovial heterogeneity captured comprehensive and discrete pathophysiological attributes of RA regarding clinical features and treatment response. This result could serve as a template for future studies to design stratified approaches for RA patients.
Evaluation of performance and carcass traits for a five-cohort All Heifer, No Cow beef production system demonstration herd
Authors: Harrison Meredith A , Arce-Cordero Jose A , Seidel George E , Archibeque Shawn L , Whittier Jack C , Rhoades Ryan D , Ahola Jason K
Published: October 2020

The All Heifer, No Cow (AHNC) beef production system is an alternative to conventional cow/calf production that involves insemination of nulliparous heifers with sexed semen to produce female calves that are early weaned at 3 mo of age. Dams are finished on a high-concentrate diet and harvested before reaching 30 mo of age. Objectives of this research were to document reproductive, feedyard, calf, and carcass performance of an AHNC herd; evaluate effects of carcass maturity on carcass quality; and determine if performance of initial cohorts (i.e., cohorts 1 and 2) differed from sustaining cohorts (i.e., cohorts 3–5). A total of 272 heifers were enrolled in the AHNC system via five annual cohorts. The system was initiated with 51 yearling, Angus-based heifers, and a replicate set (n = 56) was started 12 mo after. Heifers in cohorts 3 (n = 53), 4 (n = 56), and 5 (n = 56) were primarily offspring of prior cohorts (i.e., cohort 3 heifers born to cohort 1 females), but some were purchased to maintain inventory. Angus replacement heifers were purchased in cohorts 3 (n = 26), 4 (n = 26), and 5 (n = 28). Mean (±standard deviation) pregnancy rate at 30 d after fixed-time artificial insemination (AI) with sexed semen was 50.8% ± 9.4%, and 140-d pregnancy rate was 93.0% ± 1.5%. With AHNC, 61.0% ± 6.5% of females replaced themselves with a heifer. During finishing, average daily gain (ADG) was 1.9 ± 0.4 kg • d−1 and dry matter intake (DMI) was 14.9 ± 1.9 kg • d−1. Hot carcass weight (HCW) was 367 ± 35 kg. The USDA grading system classified 20.5% of all carcasses (n = 220) as C maturity (A00 = 100, B00 = 200, etc.), 62.4% ± 29.1% of carcasses as USDA Choice. USDA yield grade (YG) was 2.6 ± 0.7. Based on cohorts 1 and 2, there were no differences (P = 0.96) in Warner–Bratzler shear force values between A and B maturity vs. C maturity carcasses. Across all cohorts, there were no differences in USDA YG, marbling score (MA), and lean maturity between A and B maturity vs. C maturity carcasses; there were differences in age (P < 0.001), bone maturity (P < 0.001), and overall maturity (P <0.001). A comparison of initial vs. sustaining cohorts showed that initial cohorts had lower (P < 0.001) DMI, heavier (P < 0.001) HCW, and more advanced (P < 0.05) bone maturity. However, there were no differences for 30- and 140-d pregnancy rates, ADG, USDA YG, and MA between initial and sustaining cohorts. The AHNC beef production system can effectively produce female calves and quality carcasses for harvest.
Incidence and impact of hospital-acquired complications in an internal medicine unit of a reference hospital in Cameroon: a prospective cohort study
Authors: Sih Colette , Mbatchou-Ngahane Bertrand Hugo , Mboue-Djieka Yannick , Ngueng-Eke Marie C , Mbarga Nicole T , Verla Vincent S , Choukem Simeon-Pierre
Published: October 2020

Background

Hospital-acquired complications (HACs) contribute to increased morbidity, mortality and hospital costs. However, their burden is often overlooked in resource-limited settings. We sought to determine the incidence, risk factors and effects of HACs on direct medical costs.

Methods

This was a prospective cohort study conducted in the Internal Medicine inpatient ward of Douala General Hospital over 3 mo. Patients were examined daily from admission to discharge, transfer or death. Incidence of HACs was calculated and risk factors of HACs were determined using univariate and multivariate regression models.

Results

The cumulative incidence rate of HACs in 230 participants was 29.2/1000 patient-days. The incidence rate of infectious and non-infectious complications was 8.4/1000 and 20.9/1000 patient-days, respectively. The most common HAC was constipation (8.3/1000 patient-days). The most common infection was urinary tract infection (3.7/1000 patient-days). HIV infection and length of stay >8 d were significantly associated with the occurrence of HACs. Deep vein thrombosis was associated with the highest direct medical cost.

Conclusion

The incidence of HACs is high in our setting and leads to increased length of hospital stays as well as greater direct medical costs. Thus, there is a need for effective preventive strategies.
Molecular Mapping of Quantitative Trait Loci for Fusarium Head Blight Resistance in a Doubled Haploid Population of Chinese Bread Wheat
Authors: Zhu Zhanwang , Xu Xiaoting , Fu Luping , Wang Fengju , Dong Yachao , Fang Zhengwu , Wang Wenxue , Chen Yanping , Gao Chunbao , He Zhonghu , Xia Xianchun , Hao Yuanfeng
Published: October 2020

Fusarium head blight (FHB) is a destructive disease of wheat worldwide, particularly in China. To map genetic loci underlying FHB resistance, a doubled haploid (DH) population consisting of 174 lines was developed from a cross between widely grown Chinese cultivars Yangmai 16 and Zhongmai 895. The DH population and parents were evaluated in field nurseries at Wuhan in 2016 to 2017 and 2017 to 2018 crop seasons with both spray inoculation and natural infection, and at Jingzhou in 2017 to 2018 crop season with grain-spawn inoculation. The DH lines were genotyped with a wheat 660K SNP array. The FHB index, plant height, anther extrusion, and days to anthesis were recorded and used for quantitative trait loci (QTL) analysis. Seven QTL for FHB resistance were mapped to chromosome arms 3BL, 4AS, 4BS, 4DS, 5AL, 6AL, and 6BS in at least two environments. QFhb.caas-4BS and QFhb.caas-4DS co-located with semi-dwarfing alleles Rht-B1b and Rht-D1b, respectively, and were associated with anther extrusion. The other five QTL were genetically independent of the agronomic traits, indicating their potential value when breeding for FHB resistance. Based on correlations between FHB indices and agronomic traits in this population, we concluded that increasing plant height to some extent would enhance FHB resistance, that anther extrusion had a more important role in environments with less severe FHB, and that days to anthesis were independent of the FHB response when viewed across years. PCR-based markers were developed for the 3BL and 5AL QTL, which were detected in more than three environments. The InDel marker InDel_AX-89588684 for QFhb.caas-5AL was also validated on a wheat panel, confirming its effectiveness for marker-assisted breeding for improvements in FHB resistance.
Bacterial Canker of Tomato: Revisiting a Global and Economically Damaging Seedborne Pathogen
Authors: Peritore-Galve F. Christopher , Tancos Matthew A. , Smart Christine D.
Published: October 2020

The gram-positive actinobacterium Clavibacter michiganensis is the causal agent of bacterial canker of tomato, an economically impactful disease with a worldwide distribution. This seedborne pathogen systemically colonizes tomato xylem leading to unilateral leaflet wilt, marginal leaf necrosis, stem and petiole cankers, and plant death. Additionally, splash dispersal of the bacterium onto fruit exteriors causes bird’s-eye lesions, which are characterized as necrotic centers surrounded by white halos. The pathogen can colonize developing seeds systemically through xylem and through penetration of fruit tissues from the exterior. There are currently no commercially available resistant cultivars, and bactericidal sprays have limited efficacy for managing the disease once the pathogen is in the vascular system. In this review, we summarize research on epidemiology, host colonization, the bacterial genetics underlying virulence, and management of bacterial canker. Finally, we highlight important areas of research into this pathosystem that have the potential to generate new strategies for prevention and mitigation of bacterial canker.
Premix Fungicides That Reduce Development of Fruiting Bodies But Not Leaf Lesions by Stagonosporopsis citrulli on Watermelon Leaves in the Field
Authors: Keinath Anthony P.
Published: October 2020

Fungicide applications are the main method to manage gummy stem blight on watermelon (Citrullus lanatus) and other cucurbits, but it is unknown whether fungicides affect development of leaf lesions or fruiting bodies by Stagonosporopsis citrulli. Cyprodinil plus fludioxonil (Switch), cyprodinil plus difenoconazole (Inspire Super), cyprodinil (Vangard), fludioxonil (Cannonball), and difenoconazole (Inspire) were applied to watermelon in rotation with chlorothalonil (Bravo) in fall 2017, 2018, and 2019. Water and chlorothalonil applied weekly served as control treatments. All fungicides reduced disease severity (percentage of leaf area diseased) and area under the disease progress curve (AUDPC) in field plots compared with water. Cyprodinil plus fludioxonil and cyprodinil plus difenoconazole reduced disease severity and AUDPC more than chlorothalonil. Fungicides did not affect the number, diameter, expansion, or area of lesions. All fungicides reduced the number of lesions with fruiting bodies of S. citrulli compared with water (P < 0.05). Cyprodinil plus fludioxonil and cyprodinil plus difenoconazole reduced the percentage of leaf lesions with fruiting bodies, and the diameter and area of the portions of leaf lesions covered with fruiting bodies, compared with water and chlorothalonil. Premix fungicides containing cyprodinil reduced fruiting body formation by S. citrulli, which may partially explain their efficacy in managing gummy stem blight.
The elephant in the room
Authors: Roberts Deborah C.
Published: October 2020

Nurses of color refrain from speaking up when facing racism in their nursing practice from patients, White peers, coworkers, and higher-ups. Racism is the elephant in the room that no one wants to talk about. This article examines the barriers that may prevent nurses of color from speaking openly about racism and encourages all nurses to speak up and out against racism in nursing.
Anesthesiologist Age and Sex Influence Patient Perceptions of Physician Competence
Authors: Forkin Katherine T. , Dunn Lauren K. , Kotha Naveen C. , Bechtel Allison J. , Kleiman Amanda M. , Huffmyer Julie L. , Collins Stephen R. , Lyons Genevieve R. , Ma Jennie Z. , Nemergut Edward C.
Published: October 2020

Background

Uncovering patients’ biases toward characteristics of anesthesiologists may inform ways to improve the patient–anesthesiologist relationship. The authors previously demonstrated that patients prefer anesthesiologists displaying confident body language, but did not detect a sex bias. The effect of anesthesiologists’ age on patient perceptions has not been studied. In this follow-up study, it was hypothesized that patients would prefer older-appearing anesthesiologists over younger-appearing anesthesiologists and male over female anesthesiologists.

Methods

Three hundred adult, English-speaking patients were recruited in the Preanesthesia Evaluation and Testing Center. Patients were randomized (150 per group) to view a set of four videos in random order. Each 90-s video featured an older female, older male, younger female, or younger male anesthesiologist reciting the same script describing general anesthesia. Patients ranked each anesthesiologist on confidence, intelligence, and likelihood of choosing the anesthesiologist to care for their family member. Patients also chose the one anesthesiologist who seemed most like a leader.

Results

Three hundred patients watched the videos and completed the questionnaire. Among patients younger than age 65 yr, the older anesthesiologists had greater odds of being ranked more confident (odds ratio, 1.92; 95% CI, 1.41 to 2.64; P < 0.001) and more intelligent (odds ratio, 2.24; 95% CI, 1.62 to 3.11; P < 0.001), and had greater odds of being considered a leader (odds ratio, 2.62; 95% CI, 1.72 to 4.00; P < 0.001) when compared with younger anesthesiologists. The preference for older anesthesiologists was not observed in patients age 65 and older. Female anesthesiologists had greater odds of being ranked more confident (odds ratio, 1.46; 95% CI, 1.13 to 1.87; P = 0.003) and more likely to be chosen to care for one’s family member (odds ratio, 1.80; 95% CI, 1.40 to 2.31; P < 0.001) compared with male anesthesiologists. The ranking preference for female anesthesiologists on these two measures was observed among white patients and not among nonwhite patients.

Conclusions

Patients preferred older anesthesiologists on the measures of confidence, intelligence, and leadership. Patients also preferred female anesthesiologists on the measures of confidence and likelihood of choosing the anesthesiologist to care for one’s family member.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Medroxyprogesterone opposes estradiol-induced renal damage in midlife ovariectomized Long Evans rats
Authors: Zimmerman Margaret A. , Ogola Benard O. , Wilkinson Mary M. , Visniauskas Bruna , De Miguel Carmen , Daniel Jill M. , Lindsey Sarah H.
Published: October 2020

Objective:

Our laboratory previously published that long-term administration of estradiol (E2) was detrimental to the kidneys of midlife ovariectomized Long Evans rats, contrasting clinical studies in showing that menopausal hormone therapy is associated with decreased albuminuria. However, it is unknown whether this renal benefit was due to estrogen and/or the combination with progestogen. Therefore, the objective of the current study was to determine the impact of medroxyprogesterone (MPA) on E2-mediated renal damage using a rodent model.

Methods:

Female Long Evans retired breeders underwent ovariectomy at 11 months of age and were treated for 40 days with subcutaneous E2, E2+MPA or vehicle at doses mimicking that of menopausal hormone therapy (N = 5-7 per group). Systolic blood pressure was measured along with indices of renal damage and function to investigate the impact of MPA on E2-mediated renal outcomes. Renal estrogen receptor alpha and G protein-coupled estrogen receptor transcript copy numbers were measured in all treatment groups through droplet digital PCR.

Results:

Middle-aged female Long Evans rats displayed spontaneous hypertension with similar systolic blood pressures and heart weights between groups. Even though blood pressure was comparable, E2 reduced glomerular filtration rate and increased proteinuria indicating pressure-independent renal damage. Coadministration with MPA prevented E2-induced glomerular filtration rate impairment and proteinuria by promoting renal hypertrophy and preventing renal interstitial fibrosis. Both E2 and E2+MPA reduced renal estrogen receptor alpha (ERα) and increased renal G protein-coupled estrogen receptor mRNA, but neither ERα nor ERß protein was different between groups.

Conclusion:

MPA was protective against E2-induced renal damage and dysfunction in middle-aged female Long Evans rats. Assessing the impact of hormone therapy on renal outcomes may be an important clinical factor when considering treatment options for postmenopausal women.
Efficacy of progestin-only treatment for the management of menopausal symptoms: a systematic review
Authors: Dolitsky Shelley N. , Cordeiro Mitchell Christina N. , Stadler Sarah Sheehan , Segars James H.
Published: October 2020

Importance:

Menopause is associated with bothersome symptoms for many women, including mood changes, hot flushes, sleep problems, and fatigue. Progesterone is commonly prescribed in combination with estrogen therapy. Although monotherapy with progestins has been used as treatment of menopausal symptoms in women with contraindications to estrogens, the optimal route, and dosage of progestin monotherapy has not been established.

Objective:

To assess whether progestin as a standalone treatment is effective for treating vasomotor and mood symptoms associated with menopause.

Evidence review:

We conducted a systematic review using PubMed and Embase databases from January 1980 to January 2020. We included randomized controlled trials (RCTs) that investigated different forms of progestin for the treatment of vasomotor or mood symptoms associated with menopause.

Findings:

A systematic search of 892 studies identified seven RCTs involving a total of 601 patients. The available literature was heterogeneous in terms of formulation and dose of progesterone; administration ranged from 5 to 60 mg of transdermal progesterone, 10 to 20 mg oral medroxyprogesterone acetate, and 300 mg of oral micronized progesterone. Duration of treatment also differed between studies, ranging from 21 days to 12 months (median: 12 wks). Three of seven RCTs reported that progestin therapy led to an improvement of vasomotor symptoms (VMS) in postmenopausal women. The largest study administering oral progestin using 300 mg micronized progesterone reported a 58.9% improvement in VMS (vs 23.5% in placebo group, n = 133), whereas the largest study using transdermal progesterone reported no improvement (n = 230). No study reported an improvement of mood symptoms. Side effects, such as headaches and vaginal bleeding, were significant in five of seven RCTs and led to discontinuation of treatment in 6% to 21% of patients.

Conclusions and relevance:

A beneficial effect was reported in some trials with the transdermal route at longer duration and with oral treatment at higher doses for VMS for progesterone-only therapy. This report may help to inform future studies of progestin-only therapy for the treatment of menopausal symptoms.

Video Summary:

http://links.lww.com/MENO/A671.
Age, menstruation history, and the brain
Authors: Ambikairajah Ananthan , Tabatabaei-Jafari Hossein , Hornberger Michael , Cherbuin Nicolas
Published: October 2020

Objectives:

To investigate the cross-sectional association between measures of menstruation history (including menopausal status, age of menopause, age of menarche, and duration of reproductive stage) and brain volume.

Methods:

Women (aged 45 to 79 years) from the UK Biobank were included (n = 5,072) after excluding those who had (1) hysterectomy or bilateral oophorectomy, (2) ever used menopausal hormone therapy, (3) ever had a stroke, or (4) were perimenopausal. Multiple linear hierarchical regression models were computed to quantify the cross-sectional association between measures of menstruation history and brain volume. Sensitivity analysis based on propensity matching for age (and other demographic/health covariates) were applied to estimate differences in brain volumes between matched premenopausal and postmenopausal women.

Results:

Postmenopausal women had 1.06% (95% confidence interval [CI]; 1.05-1.06) and 2.17% (95% CI, 2.12-2.22) larger total brain volume (TBV) and hippocampal volumes (HV), respectively, than premenopausal women. Sensitivity analysis with age matched samples produced consistent results (TBV: 0.82%, 95% CI, 0.25-1.38; HV: 1.33%, 95% CI, 0.01-2.63). For every year increase in age above 45 years, postmenopausal women experienced 0.23% greater reduction in TBV than premenopausal women (95% CI, −0.60 to −0.14), which was not observed for HV. Moreover, every 1 year delayed onset of menopause after 45 was associated with 0.32% (95% CI, −0.35 to −0.28) and 0.31% (95% CI, −0.40 to −0.22) smaller TBV and HV, respectively. Every additional year in age of menarche was associated with 0.10% (95% CI, 0.04-0.16) larger TBV, which was not detected for HV. Similarly, every 1 year increase in duration of reproductive stage was associated with 0.09% smaller TBV (95% CI, −0.15 to −0.03), which was not detected for HV.

Conclusions:

Menopause may contribute to brain volume beyond typical aging effects. Furthermore, early age of menarche, delayed age of menopause and increasing duration of reproductive stage were negatively associated with brain volume. Further research is required to determine whether the negative association between age of menopause and HV is potentially an indicator of future vulnerability for dementia.
Ubiquitin-mediated receptor degradation contributes to development of tolerance to MrgC agonist–induced pain inhibition in neuropathic rats
Authors: Huang Qian , Ford Neil C. , Gao Xinyan , Chen Zhiyong , Guo Ruijuan , Raja Srinivasa N. , Guan Yun , He Shaoqiu
Published: October 2020

Agonists to subtype C of the Mas-related G-protein-coupled receptors (MrgC) induce pain inhibition after intrathecal (i.t.) administration in rodent models of nerve injury. Here, we investigated whether tolerance develops after repeated MrgC agonist treatments and examined the underlying mechanisms. In animal behavior studies conducted in male rats at 4 to 5 weeks after an L5 spinal nerve ligation (SNL), the ability of dipeptide MrgC agonist JHU58 (0.1 mM, 10 μL, i.t.) to inhibit mechanical and heat hypersensitivity decreased after 3 days of treatment with a tolerance-inducing dose (0.5 mM, 10 μL, i.t., twice/day). In HEK293T cells, acute treatment with JHU58 or BAM8-22 (a large peptide MrgC agonist) led to MrgC endocytosis from the cell membrane and later sorting to the membrane for reinsertion. However, chronic exposure to JHU58 increased the coupling of MrgC to β-arrestin-2 and led to the ubiquitination and degradation of MrgC. Importantly, pretreatment with TAK-243 (0.2 mM, 5 μL, i.t.), a small-molecule inhibitor of the ubiquitin-activating enzyme, during tolerance induction attenuated the development of tolerance to JHU58-induced inhibition of mechanical and heat hypersensitivity in SNL rats. Interestingly, morphine analgesia was also decreased in SNL rats that had become tolerant to JHU58, suggesting a cross-tolerance. Furthermore, i.t. pretreatment with TAK-243, which reduced JHU58 tolerance, also attenuated the cross-tolerance to morphine analgesia. These findings suggest that tolerance can develop to MrgC agonist–induced pain inhibition after repeated i.t. administrations. This tolerance development to JHU58 may involve increased coupling of MrgC to β-arrestin-2 and ubiquitin-mediated receptor degradation.
Verifying Death Reports in the Platelet Inhibition and Patient Outcomes (PLATO) Trial
Authors: Serebruany Victor , Tanguay Jean-Francois , Benavides Mario Alberto , Cabrera-Fuentes Hector , Eisert Wolfgang , Kim Moo Hyun , Yoon Junghan , Lee Cheol-Whan , Jang Kiyuk , Swan James , Marciniak Thomas ,   For the Clinical Trials Outcomes Verification Task Force
Published: October 2020

Background:

Excess vascular deaths in the PLATO trial comparing ticagrelor to clopidogrel have been repeatedly challenged by the Food and Drug Administration (FDA) reviewers and academia. Based on the Freedom of Information Act, BuzzFeed won a court order and shared with us the complete list of reported deaths for the ticagrelor FDA New Drug Application (NDA) 22–433. This dataset was matched against local patient-level records from PLATO sites monitored by the sponsor.

Study Question:

Whether FDA death data in the PLATO trial matched the local site records.

Study Design:

The NDA spreadsheet contains 938 precisely detailed PLATO deaths. We obtained and validated local evidence for 52 deaths among 861 PLATO patients from 14 enrolling sites in 8 countries and matched those with the official NDA dataset submitted to the FDA.

Measures and Outcomes:

Existence, precise time, and primary cause of deaths in PLATO.

Results:

Discrepant to the NDA document, sites confirmed 2 extra unreported deaths (Poland and Korea) and failed to confirm 4 deaths (Malaysia). Of the remaining 46 deaths, dates were reported correctly for 42 patients, earlier (2 clopidogrel), or later (2 ticagrelor) than the actual occurrence of death. In 12 clopidogrel patients, cause of death was changed to “vascular,” whereas 6 NDA ticagrelor “nonvascular” or “unknown” deaths were site-reported as of “vascular” origin. Sudden death was incorrectly reported in 4 clopidogrel patients, but omitted in 4 ticagrelor patients directly affecting the primary efficacy PLATO endpoint.

Conclusions:

Many deaths were inaccurately reported in PLATO favoring ticagrelor. The full extent of mortality misreporting is currently unclear, while especially worrisome is a mismatch in identifying primary death cause. Because all PLATO events are kept in the cloud electronic Medidata Rave capture system, securing the database content, examining the dataset changes or/and repeated entries, identifying potential interference origin, and assessing full magnitude of the problem are warranted.
Organizational Readiness of a Health System for Nurse Residency Program Accreditation
Authors: Brennen Holly
Published: October 2020

The project aim was to assess the readiness of a healthcare organization to successfully achieve national accreditation of its nurse residency program and to determine the program’s capacity to meet the accreditation standards. The only other discoverable article published related to this topic was conducted by Franquiz and Seckman (2016). This project further expands on their study and adds to the body of knowledge regarding organizational readiness to undergo nurse residency program accreditation.
Phlegmonous Psoas Muscle Infection Causing Sepsis and Death With Missing Postmortem Computed Tomography Scan Correlation
Authors: Garland Jack , O’Connor Kate , Hu Mindy , Ondruschka Benjamin , Tse Rexson
Published: October 2020

Infection of the psoas muscle is a rare pathology, which carries a high risk of sepsis and is a potential cause of death. Classic symptoms include back pain and fever and it may be diagnosed premortem on computed tomography or magnetic resonance imaging, where abscess formation may be identified as a discrete rim enhancing and low-attenuation lesion. Infections without abscess formation, such as phlegmonous infection, may be more difficult to identify however, particularly if there is absence of other nonspecific findings, such as gas bubbles. We report a case of Staphylococcus aureus phlegmonous psoas muscle causing sepsis and death with no postmortem computed tomography scan correlation, where clinical history of back pain and an unknown source of sepsis was the only prompt for psoas dissection. This case highlights a potential postmortem computed tomography blind spot in abdominal pathology and we recommend dissecting the psoas muscle if sepsis is suspected but a definitive septic focus is unable to be identified.
Framework for Multisector Alignment Research
Authors: Riley William J. , Love Kailey , Runger George , Shafer Michael S. , Pine Kathleen , Mays Glen
Published: October 2020

Context:

Public health collaboratives are effective platforms to develop interventions for improving population health. Most collaboratives are limited to the public health and health care delivery sectors; however, multisector collaboratives are becoming more recognized as a strategy for combining efforts from medical, public health, social services, and other sectors.

Program:

Based on a 4-year multisector collaborative project, we identify concepts for widening the lens to conduct multisector alignment research. The goal of the collaborative was to address the serious care fragmentation and conflicting financing systems for persons with behavioral health disorders. Our work with these 7 sectors provides insight for creating a framework to conduct multisector alignment research for investigating how alignment problems can be identified, investigated, and applied to achieve systems alignment.

Implementation:

The multisector collaborative was undertaken in Maricopa County, encompassing Phoenix, Arizona, and consisted of more than 50 organizations representing 7 sectors.

Evaluation:

We develop a framework for systems alignment consisting of 4 dimensions (alignment problems, alignment mechanisms, alignment solutions, and goal attainment) and a vocabulary for implementing multisector alignment research. We then describe the interplay and reciprocity between the 4 dimensions.

Discussion:

This framework can be used by multisector collaboratives to help identify strategies, implement programs, and develop metrics to assess impact on population health and equity.
Genital Hiatus Size and the Development of Prolapse Among Parous Women
Authors: Handa Victoria L. , Blomquist Joan L. , Carroll Megan K. , Muñoz Alvaro
Published: October 2020

Objective

In cross-sectional studies, pelvic organ prolapse is strongly associated with genital hiatus (GH) size. The objective of this study was to estimate prolapse incidence by the size of the GH among parous women followed prospectively.

Methods

Data were derived from a longitudinal study of pelvic floor disorders. Participants were followed annually for 2–9 years. Genital hiatus size and prolapse beyond the hymen were assessed with annual pelvic organ prolapse quantification examinations. Kaplan-Meier methods described prolapse-free survival as a function of GH size. Accounting for changes over time in GH size, lognormal models were used to estimate prolapse-free survival by GH size. This analysis was repeated separately for women who gave birth exclusively by cesarean versus those with at least one vaginal birth.

Results

Among 1,492 participants, median age at enrollment was 38 years; 153 (10.3%) developed prolapse over 2–9 years. The cumulative probability of prolapse increased substantially as the size of the GH increased. Lognormal models predicted that the estimated median time to develop prolapse would be 33.4 years for women with a persistent GH of 3 cm; in contrast, the estimated median time to develop prolapse would be 5.8 years for a GH of 4.5 cm or greater. Considering separately women who gave birth by cesarean versus those with at least 1 vaginal birth, GH size drastically modified prolapse risk in both birth groups.

Conclusions

Prolapse incidence is strongly associated with GH size, regardless of delivery mode. These findings suggest that a wider GH is an important predictor of future prolapse risk.
Bilateral Morning Glory Anomaly With Optic Nerve Multiple Cysts
Authors: Zhu Xuemei , Wang Yi , Liang Jianhong
Published: October 2020

We herein describe a pediatric case of bilateral morning glory anomaly whose retrobulbar cysts and renal disease were underdiagnosed, and finally, he was diagnosed with renal coloboma syndrome. We recommend patients with colobomatous optic nerve malformations undergo a complete workup to avoid missed diagnosis, which includes (i) general physical examination looking for heart defects, genitourinary, auricular, and midline facial defects among other abnormalities; (ii) simple nephrologic investigations such as routine urine test and/or renal ultrasound to check for renal hypoplasia; and (iii) neuroimaging check for cerebrovascular anomalies and midline cranial defects. Genetic testing can be a useful tool to guide the workup.
Socio-educational Impact and Psychological Distress of Medical Students amid the COVID-19 Pandemic: A Japanese Cross-Sectional Survey
Authors: Nishimura Yoshito , Ochi Kanako , Tokumasu Kazuki , Obika Mikako , Hagiya Hideharu , Kataoka Hitomi , Otsuka Fumio
Published: October 2020

The COVID-19 pandemic has negatively affected medical education. However, few data are available about medical students’ distress during the pandemic. This study aimed to provide details on how medical students had been affected by the pandemic. In this cross-sectional study, 717 medical students participated in the web-based survey. The questions included how their mental status had changed before and after the Japanese nationwide state of emergency (SOE). 65.9% (473/717) participated in the study. 29.8% (141/473) reported concerns about the shift toward online education, mostly because they thought online education could have been ineffective compared with in-person learning. Participants’ subjective mental health status significantly worsened after the SOE was lifted (p <.001). Those who had concerns about a shift toward online education had higher odds of having generalized anxiety and being depressed (OR 1.97, 95% CI 1.19 – 3.28), as did those who requested food aid and mental health care resources (OR 1.99, 95% CI 1.16 – 3.44; OR 3.56, 95% CI 2.07 – 6.15, respectively). Given our findings, the sudden shift to online education might have overwhelmed medical students. Thus, we recommend educators to inform learners that online learning is non-inferior to in-person learning, which could attenuate potential depression and anxiety.
Identification of Blood-based Biomarkers for Early Stage Parkinson’s Disease
Authors: Gao Andrew
Published: October 2020

Parkinson’s disease (PD) affects millions of people worldwide and causes symptoms such as bradykinesia and disrupted speech. Parkinson’s disease is known to be characterized by the mass death of dopaminergic neurons in the substantia nigra region. In the status quo, PD is often diagnosed at late stages because obvious motor symptoms appear after the disease has progressed far. It is advantageous to diagnose PD before the onset of motor symptoms because treatments are often more effective at early stages. While motor symptoms usually manifest when over 50% of dopaminergic neurons in the substantia nigra are already lost, molecular signatures of PD may be present at early stages in patient blood. This study aimed to analyze several gene expression studies’ data for commonly differentially expressed genes (DEGs) in the blood of early stage PD patients. 147 DEGs were identified in at least two out of three datasets and passed cut-off criteria. A protein interaction network for the DEGs was constructed and various tools were used to identify network characteristics and hub genes. PANTHER analysis revealed that the biological process “cellular response to glucagon stimulus” was overrepresented by almost 21 times among the DEGs and “lymphocyte differentiation” by 5.98 times. Protein catabolic processes and protein kinase functions were also overrepresented. ESR1, CD19, SMAD3, FOS, CXCR5, and PRKACA may be potential biomarkers and warrant further study. Overall, the findings of the present study provide insights on molecular mechanisms of PD and provide greater confidence on which genes are differentially expressed in PD. The results also are additional evidence for the role of the immune system in PD, a topic that is gaining interest in the PD research community.
Association of Serum Vitamin D Levels with Depression in Adults: A Nationwide Population-based Study in Korea
Authors: Jung Young-Eun , Dores Ashley K. , Patten Scott B. , Yatham Lakshmi N. , Lam Raymond W.
Published: October 2020

Background

Vitamin D status may be associated with depression, but there have been inconsistencies in the reported estimates. This study aimed to examine the association of vitamin D status with depression in a large general population sample.

Methods

Cross-sectional data for a representative Korean sample of 1,825 people aged 19 years or older were obtained from the nationally representative Korean National Health and Nutrition Examination Survey (2014). Depression was defined by Patient Health Questionnaire-9 (PHQ-9) scores ≥10 (moderate/severe). Logistic regression was used to estimate the associations between depression and serum 25-hydroxyvitamin D [25(OH)D] levels. Continuous serum 25(OH)D level was categorized into quartiles. Continuous PHQ-9 scores were assessed using quantile regression. Adjustments for age, sex, marital status, level of education, lowest income quartile, body mass index, level of physical activity, chronic conditions, serum creatinine level, glomerular filtration rate, and history of depression were used in the statistical analyses. Estimates of prevalence and odds ratios (OR) with 95% confidence intervals (CI) were made. Sampling weights were utilized to account for survey design effects.

Results

Individuals in the lowest serum 25(OH)D quartile level had significantly higher prevalence of depression than in the upper three quartiles (8.3% vs. 5.1%; p=0.024). No association was observed between serum 25(OH)D level and depression after adjusting for potential covariates (OR 1.48, 95%CI 0.93, 2.35; p=0.097]. However, a stronger association was observed among male respondents, with an estimated OR of 2.54 (95% CI 1.17, 5.50; p=0.018). Additionally, in the quantile regression analysis, estimates from adjusted models remained significant (β = −0.056, p=0.002).

Conclusion

While our findings support the association between lower vitamin D status and depression in Korean adults, additional studies are needed to clarify this relationship.
Does food-related cultural capital contribute to diet inequality in rural Australia? A pilot cross-sectional study
Authors: Zhang Xiaozhou , Slimings Claudia
Published: October 2020

Objective

Regional Australians have a poorer quality of diet compared to people living in metropolitan areas. Food-related cultural capital is one potential mechanism linking social determinants and nutrition. Relationships between food-related cultural capital and diet were investigated as an explanation for nutritional inequalities in regional New South Wales (NSW).

Design

A cross-sectional survey of rural NSW adults was conducted from 12th October 2019 to 31st March 2020 focusing on diet, socio-economic factors and cultural capital. Three dietary outcomes were assessed: fruit consumption, vegetable consumption, and a healthy diet score. Food-related cultural capital was analysed as objectivised and total incorporated cultural capital separately. The survey was distributed online with social media promotion.

Setting

Regional south-eastern and western NSW

Participants

448 adults (median age 57 years) of whom 93% were female.

Results

In unadjusted analysis, both total incorporated and objectivised cultural capital had strong correlations with all three diet outcomes, with low cultural capital associated with poorer nutrition. After adjusting for sociodemographic confounders, low total incorporated cultural capital showed modest associations with low fruit consumption (OR = 1.69, 95%CI = 1.00 – 2.87), low vegetable consumption (OR = 2.94, 95%CI = 1.69 – 5.11) and low diet score (OR = 3.35, 95% CI = 1.59 – 4.71).

Conclusions

Food-related cultural capital, particularly incorporated cultural capital, was independently associated with healthy food consumption in regional NSW. This new finding presents potential avenues to improve the diet of rural Australians through diet-related education, promoting food participation and reducing barriers to healthy food access.
Challenges for non-technical implementation of digital proximity tracing: early experiences from Switzerland
Authors: von Wyl Viktor
Published: October 2020

Background

Several countries have released digital proximity tracing (DPT) apps in addition to manual contact tracing (MCT) to combat the Sars-CoV-2 pandemic. The goal of DPT is to notify app users about proximity exposures to persons infected with Sars-CoV-2 so that they can self-quarantine. However, early press reports from Switzerland suggest multiple challenges for non-technical DPT implementation.

Objective

Using media articles published during the first three months after the DPT app launch to describe non-technical implementation challenges reported by different stakeholders and to map these reports to the four constructs of normalization process theory (NPT), a framework to develop and evaluate complex digital health interventions.

Methods

A Swiss media database was searched for articles on the Swiss DPT app (SwissCovid) published in German or French between 04.07.2020 and 03.10.2020. Topics were extracted manually from articles that were deemed pertinent in a structured process. Extracted topics were mapped to NPT constructs.

Results

Out of 94 articles deemed pertinent and selected for closer inspection, 38 provided unique information on implementation challenges. These challenges included unclear DPT benefits, which affected commitment and raised fears among different health system actors regarding resource competition with established pandemic mitigation measures. Moreover, media reports indicated process interface challenges such as delays or unclear responsibilities in the notification cascade, as well as misunderstandings and unmet communication needs from certain health system actors. Finally, some reports suggested misaligned incentives, not only for app usage by the public but also for process engagement by other actors in the app notification cascade. These challenges mapped well to the four constructs of NPT.

Conclusions

Early experiences from one of the earliest adopters of DPT indicate that non-technical implementation challenges warrant attention. The detected implementation challenges fit well into the framework of NPT, which seems well suited to guide the development and evaluation of complex DPT interventions.
Systematic assessment of outcomes following a genetic diagnosis identified through a large-scale research study into developmental disorders
Authors: Copeland H. , Kivuva E. , Firth H.V. , Wright C.F.
Published: October 2020

Purpose

The clinical and psychosocial outcomes associated with receiving a genetic diagnosis for developmental disorders are wide-ranging but under-studied. We sought to investigate outcomes from a subset of families who received a diagnosis through the Deciphering Developmental Disorders (DDD) study.

Method

Individuals recruited through the Peninsula Clinical Genetics Service who received a confirmed genetic diagnosis through the DDD study before August 2019 (n=112) were included in a clinical audit. Families with no identified clinical outcomes (n=16) were invited to participate in semi-structured telephone interviews.

Results

Disease-specific treatment was identified for seven probands (6%), while 48 probands (43%) were referred for further investigations or screening and 60 probands (54%) were recruited to further research. Just five families (4%) opted for prenatal testing in a subsequent pregnancy, reflecting the relatively advanced maternal age in our cohort, and 42 families (38%) were given disease-specific information or signposting to patient-specific resources such as support groups. Six interviews were performed (response rate=47%) and thematic analysis identified four major themes: reaching a diagnosis, emotional impact, family implications and practical issues.

Conclusions

Our data demonstrate that receiving a genetic diagnosis has substantial positive medical and psychosocial outcomes for the majority of patients and their families.