bluuebunny/crossref_metadata_2025 huggingface dataset:
Oops! I Shrunk the Sample Covariance Matrix Again: Blockbuster Meets Shrinkage
Authors: De Nard Gianluca
Published: June 2020

Existing shrinkage techniques struggle to model the covariance matrix of asset returns in the presence of multiple-asset classes. Therefore, we introduce a Blockbuster shrinkage estimator that clusters the covariance matrix accordingly. Besides the definition and derivation of a new asymptotically optimal linear shrinkage estimator, we propose an adaptive Blockbuster algorithm that clusters the covariance matrix even if the (number of) asset classes are unknown and change over time. It displays superior all-around performance on historical data against a variety of state-of-the-art linear shrinkage competitors. Additionally, we find that for small- and medium-sized investment universes the proposed estimator outperforms even recent nonlinear shrinkage techniques. Hence, this new estimator can be used to deliver more efficient portfolio selection and detection of anomalies in the cross-section of asset returns. Furthermore, due to the general structure of the proposed Blockbuster shrinkage estimator, the application is not restricted to financial problems.
A Survey of Tick Surveillance and Control Practices in the United States
Authors: Mader Emily M , Ganser Claudia , Geiger Annie , Harrington Laura C , Foley Janet , Smith Rebecca L , Mateus-Pinilla Nohra , Teel Pete D , Eisen Rebecca J
Published: June 2020

Tickborne diseases are an increasing public health threat in the United States. Prevention and diagnosis of tickborne diseases are improved by access to current and accurate information on where medically important ticks and their associated human and veterinary pathogens are present, their local abundance or prevalence, and when ticks are actively seeking hosts. The true extent of tick and tickborne pathogen expansion is poorly defined, in part because of a lack of nationally standardized tick surveillance. We surveyed 140 vector-borne disease professionals working in state, county, and local public health and vector control agencies to assess their 1) tick surveillance program objectives, 2) pathogen testing methods, 3) tick control practices, 4) data communication strategies, and 5) barriers to program development and operation. Fewer than half of respondents reported that their jurisdiction was engaged in routine, active tick surveillance, but nearly two-thirds reported engaging in passive tick surveillance. Detection of tick presence was the most commonly stated current surveillance objective (76.2%). Most of the programs currently supporting tick pathogen testing were in the Northeast (70.8%), Upper and Central Midwest (64.3%), and the West (71.4%) regions. The most common pathogens screened for were Rickettsia spp. (Rickettsiales: Rickettsiaceae) and bacterial and viral agents transmitted by Ixodes (Acari: Ixodidae) ticks. Only 12% of respondents indicated their jurisdiction directly conducts or otherwise financially supports tick control. Responses indicated that their ability to expand the capacity of tick surveillance and control programs was impeded by inconsistent funding, limited infrastructure, guidance on best practices, and institutional capacity to perform these functions.
Aerobic Metabolism Alterations as an Evidence of Underlying Deltamethrin Resistance Mechanisms in Triatoma infestans (Hemiptera: Reduviidae)
Authors: Rolandi Carmen , Roca-Acevedo Gonzalo , Schilman Pablo E , Germano Mónica D
Published: June 2020

Triatoma infestans (Klug, 1834), the main vector of Chagas disease in Latin America, is regularly controlled by spraying the pyrethroid deltamethrin, to which some populations have developed resistance. The three main mechanisms of resistance are 1) metabolic resistance by overexpression or increased activity of detoxifying enzymes, 2) target site mutations, and 3) cuticle thickening/modification. We use open-flow respirometry to measure real-time H2O loss rate (V˙H2O) and CO2 production rate (V˙CO2), on nymphs from susceptible and resistant populations before and after exposure to the insecticide to understand the underlying mechanisms of resistance in live insects. Lack of differences in V˙H2O between populations suggested that cuticular thickness/composition is not acting as a relevant resistance mechanism. Similarly, there was no difference in resting V˙CO2, suggesting a trade-off between resistance mechanisms and other physiological processes. The increment in V˙CO2 after application of deltamethrin was similar in both populations, which suggested that while enhanced enzymatic detoxification may play a role in resistance expression in this population, the main mechanism involved should be a passive one such as target site mutations. Open-flow respirometry provided useful evidence for evaluating the mechanisms involved in deltamethrin resistance. Using this technique could improve efficiency of scientific research in the area of insecticide resistance management, leading to a faster decision making and hence improved control results.
Indian Princely States and the 19th-century Transformation of the Law of Nations
Authors: Singh Prabhakar
Published: June 2020

The role of the roughly 600 Indian princely kingdoms in the transformation of the law of nations into international law during the 19th century is an overlooked episode of international legal history. The Indian princely states effected a gradual end of the Mughal and the Maratha confederacies while appropriating international legal language. The Privy Council—before and after 1858—sanctified within common law as the acts of state, both, the seizure of territories from Indian kings and the ossification of encumbrances attached to the annexed territories. After the Crown takeover of the East India Company in 1858, the British India Government carefully rebooted, even mimicked, the native polyandric relationship of the tribal chiefs, petty states and semi-sovereigns with the Mughal–Maratha complex using multi-normative legal texts. Put down in the British stationery as engagements, sunnuds and treaties, these colonial texts projected an imperially layered nature of the native sovereignty. I challenge the metropole's claims of a one-way export to the colonies of the assumed normative surpluses. I argue that the periphery while responding to a ‘jurisdictional imperialism' upended interational law's civilisation-giving thesis by exporting law to the metropole.
Tumor volume shrinkage during stereotactic body radiotherapy is related to better prognoses in patients with stage I non-small-cell lung cancer
Authors: Vu Nam , Onishi Hiroshi , Saito Masahide , Kuriyama Kengo , Komiyama Takafumi , Marino Kan , Araya Masayuki , Aoki Shinichi , Saito Ryo , Nonaka Hotaka , Funayama Satoshi , Watanabe Hiroaki , Sano Naoki
Published: June 2020

The purpose of the study was to investigate the association between tumor volume changes during stereotactic body radiation therapy (SBRT) and prognoses in stage I non-small-cell lung cancer (NSCLC). This retrospective review included stage I NSCLC patients in whom SBRT was performed at a total dose of 48.0–50.5 Gy in four or five fractions. The tumor volumes observed on computed tomography (CT) simulation and on the CT performed at the last treatment session using a CT-on-rails system were measured and compared. Then, the tumor volume changes during the SBRT period were measured and assessed for their association with prognoses (overall survival, local control, lymph node metastases and distant metastases). A total of 98 patients with a mean age of 78.6 years were enrolled in the study. The T-stage was T1a in 42%, T1b in 32% and T2a in 26% of the cases. The gross tumor volume (GTV) shrank and increased ≥10% in 23 (23.5%) and 36 (36.7%) of the cases, respectively. The 5-year local control and overall survival rates in the groups with a tumor shrinkage of ≥10% vs the group with a shrinkage of <10% were 94.7 vs 70.8% and 85.4 vs 47.6%, respectively; these differences were significant, with a P-value < 0.05. During a short SBRT period, the tumor shrank or enlarged in a small number of cases. A decrease of ≥10% in the GTV during SBRT was significantly related to better overall survival and local control.
Role and limitations of the geometric mean method regarding head rotation in salivary gland scintigraphy: a phantom study
Authors: Chen I-Feng , Lin Li-Fan , Lin Chun-Long , Chung Tzu-Jou , Tseng Ta-Wei , Chiu Chuang-Hsin
Published: June 2020

To investigate the possible influence of head rotation on the results of salivary gland scintigraphy, a phantom study was designed to simulate clinical salivary gland scintigraphy. The quantitative accuracy of regional activity counts was compared for two data acquisition methods involving head rotation: (i) an anterior planar projection-only (ANT) method and (ii) a geometric mean (GM) method using both the anterior and posterior planar projections. The roles and limitations of the GM and ANT methods when used at different head rotation angles were examined. Parallel planar projections of a head phantom with four salivary gland simulators, containing 3.7 MBq 99mTc-sodium pertechnetate, at various rotational settings were acquired using a dual-head gamma camera. The difference between the standard activity counts (no phantom rotation) and the activity counts affected by the phantom rotation was calculated and defined as the rotational bias that decreased the accuracy of activity quantification. For small-angle rotation (≤10°), use of the GM method decreased the bias for all salivary gland simulators. In contrast, the bias of large-angle rotation (>10°) between four salivary gland simulators became conspicuous and complex in both methods. This bias may reflect different attenuation effects caused by displacement of the structures. Our data suggest that the GM method can be used when the head rotation angle is small (≤10°); however, when the head rotation angle is >10°, the non-negligible influence of head rotation should be considered during image acquisition.
Epidemiology of bloodstream Candida species in a Spanish tertiary care hospital as a guide for implementation of T2MR (T2CANDIDA®) for rapid diagnosis of candidemia
Authors: Falces-Romero Iker , Romero-Gómez María Pilar , Moreno-Ramos Francisco , Mingorance Jesús , García-Rodríguez Julio , Cendejas-Bueno Emilio
Published: June 2020

The aim of this work was to study the epidemiology of candidemia in our hospital in order to determine whether the T2MR system might be a useful tool for early diagnosis of candidemia in selected units. We perform a retrospective review of all candidemia episodes registered in the last 12 years in selected units of our hospital in adult and pediatric patients. Candida species and antifungal susceptibility patterns were registered. A total of 686 isolates were registered, of which 625 were infections due to the five most common species of Candida. C. albicans (45.6%) and C. parapsilosis (33.1%) were the predominant species found in our institution. In adults these species were closely followed by C. glabrata (12–21%) in all units. While in pediatric medical and intensive care units (PICU), these species were followed by other uncommon yeasts. Resistance rates to triazoles were low in C. albicans and C. parapsilosis. In C. glabrata and C. tropicalis the resistance rates to fluconazole ranged from 10.86 to 6.67%. Resistance rates for echinocandins were very low and all strains were susceptible to amphotericin B. T2Candida® might be useful to guide antifungal targeted treatment and discontinuation of antifungal empirical treatment in those units where the five most common Candida species represent more than the ninety percent of the isolates. The selection of medical and surgical units should be based on local epidemiology and antifungal susceptibility patterns. Incidence should be taken into account in order to make clinical decisions based on negative results.

Lay Abstract

T2Candida® might be useful selectively in clinical units according to their local epidemiology, antifungal resistance patterns, and incidence of candidemia. It optimizes the clinical value of positive results supporting decisions about targeted therapies or discontinuations based on negative results.
A systematic investigation of the association between network dynamics in the human brain and the state of consciousness
Authors: Crone Julia S , Lutkenhoff Evan S , Vespa Paul M , Monti Martin M
Published: June 2020

An increasing amount of studies suggest that brain dynamics measured with resting-state functional magnetic resonance imaging (fMRI) are related to the state of consciousness. However, the challenge of investigating neuronal correlates of consciousness is the confounding interference between (recovery of) consciousness and behavioral responsiveness. To address this issue, and validate the interpretation of prior work linking brain dynamics and consciousness, we performed a longitudinal fMRI study in patients recovering from coma. Patients were assessed twice, 6 months apart, and assigned to one of two groups. One group included patients who were unconscious at the first assessment but regained consciousness and improved behavioral responsiveness by the second assessment. The other group included patients who were already conscious and improved only behavioral responsiveness. While the two groups were matched in terms of the average increase in behavioral responsiveness, only one group experienced a categorical change in their state of consciousness allowing us to partially dissociate consciousness and behavioral responsiveness. We find the variance in network metrics to be systematically different across states of consciousness, both within and across groups. Specifically, at the first assessment, conscious patients exhibited significantly greater variance in network metrics than unconscious patients, a difference that disappeared once all patients had recovered consciousness. Furthermore, we find a significant increase in dynamics for patients who regained consciousness over time, but not for patients who only improved responsiveness. These findings suggest that changes in brain dynamics are indeed linked to the state of consciousness and not just to a general level of behavioral responsiveness.
Measuring change in health-related quality of life: the impact of different analytical methods on the interpretation of treatment effects in glioma patients
Authors: Coomans Marijke B , Taphoorn Martin J B , Aaronson Neil K , Baumert Brigitta G , van den Bent Martin , Bottomley Andrew , Brandes Alba A , Chinot Olivier , Coens Corneel , Gorlia Thierry , Herrlinger Ulrich , Keime-Guibert Florence , Malmström Annika , Martinelli Francesca , Stupp Roger , Talacchi Andrea , Weller Michael , Wick Wolfgang , Reijneveld Jaap C , Dirven Linda
Published: June 2020

Background

Different analytical methods may lead to different conclusions about the impact of treatment on health-related quality of life (HRQoL). This study aimed to examine 3 different methods to evaluate change in HRQoL and to study whether these methods result in different conclusions.

Methods

HRQoL data from 15 randomized clinical trials were combined (CODAGLIO project). Change in HRQoL scores, measured with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and BN20 questionnaires, was analyzed in 3 ways: (1) at the group level, comparing mean changes in scale/item scores between treatment arms, (2) at the patient level per scale/item, calculating the percentage of patients that deteriorated, improved, or remained stable per scale/item, and (3) at the individual patient level, combining all scales/items.

Results

Baseline and first follow-up HRQoL data were available for 3727 patients. At the group scale/item level, only the item “hair loss” showed a significant and clinically relevant change (ie, ≥10 points) over time, whereas change scores on the other scales/items were statistically significant only (all P < .001; range in change score, 0.1-6.2). Although a large proportion of patients had stable HRQoL over time (range, 27%-84%) on the patient level per scale/item, many patients deteriorated (range, 6%-43%) or improved (range, 8%-32%) on a specific scale/item. At the individual patient level, the majority of patients (86%) showed both deterioration and improvement, whereas only 1% remained stable on all scales.

Conclusions

Different analytical methods of changes in HRQoL result in distinct conclusions of treatment effects, all of which may be relevant for informing clinical decision making.
Improving immunization uptake rates among Gypsies, Roma and Travellers: a qualitative study of the views of service providers
Authors: Mytton Julie , Bedford Helen , Condon Louise , Jackson Cath ,   UNITING team
Published: June 2020

Background

Gypsies, Roma and Travellers are at risk of low uptake of routine immunizations. Interventions to improve uptake in these communities are seldom evaluated. As part of a qualitative study exploring barriers and facilitators to immunization uptake in Travellers, we report service provider (SP) perspectives.

Methods

We interviewed immunization SPs working with six Traveller communities across four UK cities. Participants included frontline staff and those with strategic or commissioning roles. Semi-structured interviews explored perceived attitudes of Travellers to vaccinations, local service delivery, and opportunities and challenges to improving uptake. Audio-recordings were transcribed, analyzed thematically and mapped to a socio-ecological model of health.

Results

39 SPs participated. Four overarching themes were identified: building trusting relationships between SPs and Travellers; facilitating attendance at appointments; improving record keeping and monitoring and responding to local and national policy change. Travellers were perceived as largely supportive of immunizations, though system and organizational processes were recognized barriers to accessing services.

Conclusions

Findings were broadly consistent across Traveller groups and settings. The barriers identified could often be addressed within existing infrastructure, though require system or policy change. Development of a culturally competent system appears important to enable equity in access to immunizations for Travellers.
Perceptions of public on the COVID-19 outbreak in Singapore: a qualitative content analysis
Authors: Shorey Shefaly , Ang Emily , Yamina Amira , Tam Clarence
Published: June 2020

Background

Singapore is among the several countries affected by the COVID-19 outbreak. The outbreak has elicited panic and unease among Singapore’s public. This study aimed to analyze the comments left on local media news outlets to find common concerns and discuss potential new measures that can be developed to reduce panic and support for Singapore’s public during and beyond COVID-19.

Methods

A qualitative content analysis on the comments on relevant news articles from the Facebook pages of six online local news publications dated from 23 January 2020 to the 3 April 2020 was carried out.

Results

Five common themes were derived 1: fear and concern (35.42%), 2 panic buying and hoarding (21.21%), 3 reality and expectations about the situation (20.24%), 4 staying positive amid the ‘storm’ (10.07%) and 5 worries about the future (5.01%). The analysis revealed that fear and concern were the main reasons behind the public’s responses.

Conclusion

Clear communication between the government and the public is one of the best ways to maintain calm among the public and to contribute to greater social cooperation. Timely updates and support measures from the government further help to maintain social peace and cohesion.
Enhancement of BMP-2 and VEGF carried by mineralized collagen for mandibular bone regeneration
Authors: Liu Kun , Meng Chun-Xiu , Lv Zhao-Yong , Zhang Yu-Jue , Li Jun , Li Ke-Yi , Liu Feng-Zhen , Zhang Bin , Cui Fu-Zhai
Published: June 2020

Repairing damage in the craniofacial skeleton is challenging. Craniofacial bones require intramembranous ossification to generate tissue-engineered bone grafts via angiogenesis and osteogenesis. Here, we designed a mineralized collagen delivery system for BMP-2 and vascular endothelial growth factor (VEGF) for implantation into animal models of mandibular defects. BMP-2/VEGF were mixed with mineralized collagen which was implanted into the rabbit mandibular. Animals were divided into (i) controls with no growth factors; (ii) BMP-2 alone; or (iii) BMP-2 and VEGF combined. CT and hisomputed tomography and histological staining were performed to assess bone repair. New bone formation was higher in BMP-2 and BMP-2-VEGF groups in which angiogenesis and osteogenesis were enhanced. This highlights the use of mineralized collagen with BMP-2/VEGF as an effective alternative for bone regeneration.
Trauma-informed exercise for women survivors of sexual violence
Authors: Pebole Michelle , Gobin Robyn L , Hall Katherine S
Published: June 2020

Compared to their male counterparts, women experience alarmingly high rates of sexual violence (SV). Nearly 20% of women in the USA have been victims of SV, and prevalence of sexual assault among female service members is reported to be even higher, up to 50%. SV results in negative health outcomes like posttraumatic stress disorder, depression, obesity, poor body image, and pain-related disability. Exercise has been shown to positively impact both mental and physical health outcomes in populations experiencing posttraumatic symptoms, yet women survivors of SV are often excluded from exercise trials in trauma-affected populations. The purpose of this paper is to comment on the importance of incorporating women-specific trauma-informed principles in the content and delivery of exercise interventions in trauma-affected populations, particularly as it relates to SV. Researchers discuss the implications of female-specific and trauma-informed exercise considerations for SV survivors. This commentary highlights the need for trauma-informed implementation efforts and outcome measurements in exercise interventions involving women affected by SV. Researchers call for (a) increased qualitative work on trauma-specific implementation efforts across exercise intervention domains and (b) increased assessment of trauma-specific outcomes in exercise trials.
More students doing more maths? Student attitudes to mathematics and perceptions of its teaching in a new post-compulsory course
Authors: Homer Matt , Mathieson Rachel , Tasara Innocent , Banner Indira
Published: June 2020

In England, a relatively new set of post-16 qualifications has been developed under the umbrella term ‘Core Maths’, with a focus on the application of mathematics in context, including the kinds of mathematics needed to support other subjects, to provide a sound basis for the mathematical demands of higher education and employment and to develop problem-solving skills for use in life. The UK government has an ambition that all post-16 students should be studying some mathematics, and Core Maths was designed in part with this aspiration in mind. In this paper, longitudinal questionnaire data from over 100 Core Maths students in 13 case study institutions are analysed to measure students’ views of teaching as transmissionist, their mathematical dispositions and self-identification and how these change over a year of studying Core Maths. We find some evidence that pedagogy in lessons is perceived as being less transmissionist than it was in school mathematics pre-16. There is also some evidence of a negative change in students’ mathematical dispositions over a year of Core Maths. We conclude that supporting teachers in embedding new pedagogical approaches remains a challenge and that this issue could inhibit the growth of new qualifications like Core Maths.
Guillain–Barré Syndrome Associated with SARS-CoV-2 Infection in a Pediatric Patient
Authors: Frank Carlos Henrique Michiles , Almeida Taynná Vernalha Rocha , Marques Elyana Almeida , de Sousa Monteiro Quezia , Feitoza Pablo Vinícius Silveira , Borba Mayla Gabriela Silva , Vasconcelos Heline Lira , de Souza Bastos Michele , Lacerda Marcus Vinicius Guimarães
Published: June 2020

We report the case of a 15-year-old male patient presenting frontal headaches with retro-orbital pain accompanied by fever evolving to weakness and pain of the lower limbs, which ascended to upper limbs. A COVID-19 rapid test (IgG and IgM) and nasopharyngeal swab polymerase chain reaction (PCR) was positive for SARS-CoV-2. The blood tests, cerebral spinal fluid (CSF) analysis and CSF aerobic culture revealed no abnormalities. PCR testing of the CSF was negative for the most prevalent etiologies as well as for SARS-CoV-2. Electroneurography study was compatible with the acute motor axonal neuropathy variant of Guillain–Barré syndrome. No cases involving young patients have been presented to date. Therefore, this is the first reported pediatric case of SARS-CoV-2 infection associated with GBS. Evidence reveals that SARS-CoV-2 infection is not limited to the respiratory tract. Neurotropism could explain this important neurologic manifestation of COVID-19 in children.
Identification of a Novel Isolate of Alfalfa virus S from China Suggests a Possible Role of Seed Contamination in the Distribution of the Virus
Authors: Nemchinov Lev G. , Grinstead Samuel
Published: June 2020

Recently, alfalfa virus S (AVS), a new species in the family Alphaflexiviridae, was identified in alfalfa samples originating from Sudan, northern Africa. Here, we report on the identification and complete genomic sequence of an AVS isolate found in 7-day-old seedlings grown from alfalfa seeds acquired from China. The Chinese isolate of AVS differed in its nucleotide sequence from the Sudanese isolate by 8.6%. The detection of AVS in alfalfa seedlings developed from the germinated seeds may indicate a potential role of seed transmission in the distribution of this virus. The results obtained suggest that AVS may be far more widespread than previously thought.
Effect of NSAID Use on Bone Healing in Pediatric Fractures: A Preliminary, Prospective, Randomized, Blinded Study
Authors: Nuelle Julia A.V. , Coe Kelsie M. , Oliver Harvey A. , Cook James L. , Hoernschemeyer Daniel G. , Gupta Sumit K.
Published: June 2020

Background:

This study aimed to investigate if nonsteroidal anti-inflammatory drugs (NSAIDs) used in the acute phase of bone healing in children with fractures result in delayed union or nonunion as compared with patients who do not take NSAIDs for pain control during this same time period.

Methods:

In this prospective, randomized, parallel, single-blinded study, skeletally immature patients with long bone fractures were randomized to 1 of 2 groups for their postfracture pain management. The NSAID group was prescribed weight-based ibuprofen, whereas the control group was not allowed any NSAID medication and instead prescribed weight-based acetaminophen. Both groups were allowed to use oxycodone for breakthrough pain. The primary outcome was fracture healing assessed at 2, 6, and 10 weeks.

Results:

One-hundred-two patients were enrolled between February 6, 2014 and September 23, 2016. Ninety-five patients (with 97 fractures) completed a 6-month follow-up (46 patients with 47 fractures in the control group and 49 patients 50 fractures in the NSAID group). None achieved healing at 1 to 2 weeks. By 6 weeks, 37 of 45 patients (82%) of control group and 46 out of 50 patients (92%) of ibuprofen group had healed fractures (P=0.22). At 10 to 12 week follow-up, 46 (98%) of the control group fractures were healed and 50 (100%) of the ibuprofen group fractures were healed. All were healed by 6 months. Healing was documented at a mean of 40 days in the control group and 31 days in the ibuprofen group (P=0.76). The mean number of days breakthrough oxycodone was used was 2.4 days in the control group and 1.9 days in the NSAID group (P=0.48).

Conclusion:

Ibuprofen is an effective medication for fracture pain in children and its use does not impair clinical or radiographic long bone fracture healing in skeletally immature patients.

Level of Evidence:

Level I—therapeutic.
The Evaluation of Retinal Nerve Fiber Layer and Ganglion Cell Complex Thickness in Adult Offspring of Primary Open-angle Glaucoma Patients
Authors: Bilgin Sinan
Published: June 2020

Precis:

In the adult offspring of glaucoma patients, retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness, especially in the inferior quadrant, were significantly decreased. This finding in the adult offspring of glaucoma patients may be important in evaluating the course of glaucoma disease.

Purpose:

The aim of this study was to investigate RNFL and GCC thickness in adult offspring of primary open-angle glaucoma (POAG) patients and to compare the results with individuals without a family history for glaucoma disease.

Materials and Methods:

This was a cross-sectional observational study. Forty eyes of 40 individuals with self-reported family history for proven POAG and 40 eyes of 40 healthy individuals without a family history for glaucoma disease were included in the study. RNFL and macular GCC thickness were measured by spectral-domain optical coherence tomography, and the results were compared between the 2 groups.

Results:

In adult offspring of patients with POAG, RNFL and GCC thickness were thinner in all quadrants. Average RNFL and GCC decreased significantly in adult offspring of patients with POAG (P=0.039 and 0.015, respectively). Thinning in RNFL and GCC thickness was especially significant in the inferior quadrant (P=0.024 and 0.039, respectively). There was no significant difference between the groups in terms of mean deviation and pattern standard deviation values (P=0.064 and 0.091, respectively).

Conclusions:

In adult offspring of POAG patients, especially in the inferior quadrant, the RNFL and GCC thickness are significantly lower than in subjects without a family history. Prospective, controlled clinical trials with longer follow-up are needed to better understand whether these changes are an early indicator of glaucoma, and the progression of glaucoma disease.
Diurnal Measurements of Macular Thickness and Vessel Density on OCT Angiography in Healthy Eyes and Those With Ocular Hypertension and Glaucoma
Authors: Milani Paolo , Bochicchio Sara , Urbini Lara E. , Bulone Ennio , Callegarin Stefania , Pisano Luca , Scotti Lorenza , Zambon Antonella , Bergamini Fulvio
Published: June 2020

Precis:

Macular superficial capillary plexus (SCP) and thickness are reduced in eyes with glaucoma and ocular hypertension, but do not change significantly during the day. No relationships with age, intraocular pressure, systemic hypertension, or axial length were found.

Purpose:

The purpose of this study was to evaluate diurnal differences in retinal thickness and vessel density (VD) of the macular SCP and deep capillary plexus (DCP) using optical coherence tomography angiography among 3 groups: eyes with glaucoma, eyes with ocular hypertension, and healthy eyes.

Methods:

A consecutive series of individuals was recruited prospectively. Optical coherence tomography angiography was performed in the morning and in the evening.

Results:

Forty eyes from 23 individuals with glaucoma (58.35±6 y), 52 eyes from 32 individuals with ocular hypertension (58.84±7 y), and 73 eyes from 44 controls (57.84±6 y) were enrolled. Morning and evening measurements of all SCP-VD and retinal thickness parameters were statistically significantly different (P<0.04) among the 3 groups of eyes. None of the DCP-VD parameters were significantly different. Daily changes in SCP-VD, DCP-VD, and retinal thickness among the groups of eyes were not statistically significant. Systemic hypertension, age, axial length, and diurnal changes in intraocular pressure were not significantly associated with diurnal fluctuations of SCP-VD, DCP-VD, or retinal thickness (P>0.19). A positive linear correlation in diurnal changes was found between SCP-VD and DCP-VD in the fovea and in the parafovea (r=0.5567 and 0.5892, respectively) and between SCP-VD and retinal thickness in the fovea and in the parafovea (r=−0.2288 and 0.2418, respectively).

Conclusions:

Macular SCP-VD and thickness are reduced in eyes with glaucoma and ocular hypertension. Although diurnal changes in SCP-VD, DCP-VD and macular thickness were not significant among the groups, some linear correlations in increasing or decreasing values of the investigated parameters were found.
Associations of Abdominal Pain and Psychosocial Distress Measures With Health-Related Quality-of-Life in Pediatric Healthy Controls and Irritable Bowel Syndrome
Authors: Hollier John M. , Czyzewski Danita I. , Self Mariella M. , Liu Yan , Weidler Erica M. , van Tilburg Miranda A.L. , Varni James W. , Shulman Robert J.
Published: June 2020

Background:

Children with irritable bowel syndrome (IBS) have lower health-related quality-of-life (HRQOL) than healthy controls (HC). Abdominal pain and psychosocial distress are negatively associated with HRQOL, although their relative effect is unclear.

Aim:

The aim of this study was to compare the relative associations of abdominal pain and psychosocial distress with HRQOL in HC and IBS.

Study:

Baseline abdominal pain, psychosocial distress, and HRQOL measures were obtained from HC and IBS pediatric clinical trial participants. Regression assessed which measures were most strongly associated with Physical and Psychosocial HRQOL separately by group. Interaction analyses examined group differences in the associations of abdominal pain and psychosocial distress with HRQOL.

Results:

Eight-five HC and 213 children with IBS participated. Somatization was most strongly associated with Physical HRQOL in HC, and functional disability was most strongly related in IBS. With respect to Psychosocial HRQOL, somatization was most strongly associated for both HC and IBS; depression was also significantly associated in HC. The strength of association between somatization and Physical HRQOL differed between groups; the negative association was less pronounced for IBS than HC. The association between functional disability and both Physical and Psychosocial HRQOL differed significantly between groups; the negative associations were more pronounced for IBS than HC.

Conclusions:

Multiple psychosocial distress measures, including somatization, were associated with HRQOL in children with IBS; HRQOL in HC was driven consistently by somatization, to the exclusion of other psychosocial concerns. The associations of somatization and functional disability with HRQOL are distinctly different between HC and IBS. This knowledge supports utilization of psychosocial interventions to improve overall well-being for children with IBS.
Safety of Rapid Infliximab Infusions in Children
Authors: van Wassenaer Elsa A. , van Oosterhout Janneke P.M. , Daams Joost G. , van den Berg Merlijn J.M. , van der Lee Hanneke , D’Haens Geert R. , de Meij Tim G.J. , Benninga Marc A. , Koot Bart G.P.
Published: June 2020

Objectives:

The aim of the study was to assess whether the incidence of infusion reactions (IR) increases after rapid (≤1 hour) infliximab (IFX) infusions, compared with standard (2–3 hour) infusions in children.

Methods:

Systematic review including studies describing the number of IR after rapid IFX infusion in children ages 0 to 18 years.

Results:

Four records were included (3 retrospective, n = 498, 347 standard infusions, 3703 rapid infusions). Reported incidences of IR ranged from 0% to 2% of infusions in standard groups (reported 95% confidence intervals [CIs] ranged from 0% to 7%) and from 0% to 2% of infusions in rapid groups (reported 95% CIs ranged from 0% to 12%). None of the studies included reported a significant difference in incidence of IR between the 2 groups.

Conclusions:

There is insufficient evidence to conclude whether the rate of IR after rapid IFX increases. The consistent finding of no increase in IR in all studies and the low rate of observed IR suggests there is no significant difference in rate of IR.
Association Between Physician Burnout and Self-reported Errors: Meta-analysis
Authors: Owoc Jakub , Mańczak Małgorzata , Jabłońska Magdalena , Tombarkiewicz Marek , Olszewski Robert
Published: June 2020

Objectives

Burnout among physicians is an increasingly recognized phenomenon affecting different aspects of patient care and safety. This meta-analysis quantifies association of burnout and its subscales with self-reported medical errors among physicians.

Methods

This meta-analysis followed the principles formulated in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analyses of Observational Studies. The MEDLINE, PubMed, Web of Science, PsycInfo, and Eric databases were searched until February 5, 2019, using various combinations of key terms without any language restrictions: burnout, physicians, error, safety, and quality. Reference lists of selected studies were hand searched. Data were extracted from published reports. All quantitative studies reporting prevalence of burnout and its association with self-reported errors among physicians were considered. The analyses of heterogeneity (Cochran Q, I
2), publication bias (Begg-Mazumdar and Egger), three subgroups, and sensitivity were performed. The effect of overall burnout and Maslach Burnout Inventory subscales on self-reported errors was calculated as odds ratios with 95% confidence interval.

Results

Thirteen studies on 20,643 physicians and residents were included. The overall burnout among participants was associated with a significantly increased risk of self-reported errors (odds ratio = 2.72, 95% confidence interval = 2.19–3.37). Emotional exhaustion, depersonalization, and personal accomplishment were all independently predicting factors of self-reported errors. Cochran Q test and inconsistency index I
2 were as follows: Q = 27.2; P = 0.0013, I
2 = 67% (36%–83%).

Conclusions

The results provide evidence that not only overall burnout but also its subscales independently are to be associated with a significantly increased risk of self-reported errors among physicians. As self-reported errors may translate into different types of adverse events, this strong and unequivocal association should be of major concern to healthcare organizations.
A Machine Learning Approach to Reclassifying Miscellaneous Patient Safety Event Reports
Authors: Fong Allan , Behzad Shabnam , Pruitt Zoe , Ratwani Raj M.
Published: June 2020

Background and Objectives

Medical errors are a leading cause of death in the United States. Despite widespread adoption of patient safety reporting systems to address medical errors, making sense of the reports collected in these systems is challenging in practice. Event classification taxonomies used in many reporting systems can be complex and difficult to understand by frontline reporters, leading reporters to classify reports as “miscellaneous” as opposed to assigning a specific event-type category, which may facilitate analysis.

Methods

To assist patient safety analysts in their analysis of “miscellaneous” reports, we developed an ensemble machine learning natural language processing model to reclassify these reports. We integrated the model into a clinical workflow dashboard, evaluated user feedback, and compared differences in user thresholds for model performance.

Results and Conclusions

Integrating an ensemble model to classify “miscellaneous” event reports with an interactive visualization was helpful to patient safety analysts review “miscellaneous” reports. However, patient safety analysts have different thresholds for model reclassification depending on their role and experience with “miscellaneous” event reports.
A Novel Machine Learning-derived Radiomic Signature of the Whole Lung Differentiates Stable From Progressive COVID-19 Infection
Authors: Fu Liping , Li Yongchou , Cheng Aiping , Pang PeiPei , Shu Zhenyu
Published: June 2020

Objective:

This study aimed to use the radiomics signatures of a machine learning-based tool to evaluate the prognosis of patients with coronavirus disease 2019 (COVID-19) infection.

Methods:

The clinical and imaging data of 64 patients with confirmed diagnoses of COVID-19 were retrospectively selected and divided into a stable group and a progressive group according to the data obtained from the ongoing treatment process. Imaging features from whole-lung images from baseline computed tomography (CT) scans were extracted and dimensionality reduction was performed. Support vector machines were used to construct radiomics signatures and to compare differences between the 2 groups. We also compared the differences of signature scores in the clinical, laboratory, and CT image feature subgroups and finally analyzed the correlation between the radiomics features of the constructed signature and the other features including clinical, laboratory, and CT imaging features.

Results:

The signature has a good classification effect for the stable group and the progressive group, with area under curve, sensitivity, and specificity of 0.833, 80.95%, and 74.42%, respectively. Signature score differences in laboratory and CT imaging features between subgroups were not statistically significant (P>0.05); cough was negatively correlated with GLCM Entropy_angle 90_offset4 (r=−0.578), but was positively correlated with ShortRunEmphhasis_AllDirect_offset4_SD (r=0.454); C-reactive protein was positively correlated with Cluster Prominence_ AllDirect_offset 4_ SD (r=0.47).

Conclusion:

The radiomics signature of the whole lung based on machine learning may reveal the changes of lung microstructure in the early stage and help to indicate the progression of the disease.
Dose and duration of interferon γ pre-licensing interact with donor characteristics to influence the expression and function of indoleamine-2,3-dioxygenase in mesenchymal stromal cells
Authors: Boyt Devlin T. , Boland Lauren K. , Burand Anthony J. , Brown Alex J. , Ankrum James A.
Published: June 2020

Human mesenchymal stromal cells (MSCs) are a leading cell therapy candidate for the treatment of immune and inflammatory diseases due to their potent regulation of immune cells. MSC expression of indoleamine-2,3-dioxygenase (IDO) upon interferon γ (IFNγ) exposure has been proposed as both a sentinel marker and key mediator of MSC immunomodulatory potency. Rather than wait for
in vivo
exposure to cytokines, MSCs can be pre-licensed during manufacturing to enhance IDO expression. In this study, we systematically examine the relative role that the dose of IFNγ, the duration of pre-licensing and the donor of origin play in dictating MSC production of functional IDO. We find that across three human MSC donors, MSCs increase their expression of IDO in response to both increased dose of IFNγ and duration of pre-licensing. However, with extended pre-licensing, the expression of IDO no longer predicts MSCs ability to suppress activated peripheral blood mononuclear cells. In addition, pre-licensing dose and duration are revealed to be minor modifiers of MSCs inherent potency, and thus cannot be manipulated to boost poor donors to the levels of high-performing donors. Thus, the dose and duration of pre-licensing should be tailored to optimize performance of specific donors and an emphasis on donor selection is needed to realize significant benefits of pre-licensing.
Microglia: sculptors of neuropathic pain?
Authors: Ward Harry , West Steven J.
Published: June 2020

Neuropathic pain presents a huge societal and individual burden. The limited efficacy of current analgesics, diagnostic markers and clinical trial outcome measures arises from an incomplete understanding of the underlying mechanisms. A large and growing body of evidence has established the important role of microglia in the onset and possible maintenance of neuropathic pain, and these cells may represent an important target for future therapy. Microglial research has further revealed their important role in structural remodelling of the nervous system. In this review, we aim to explore the evidence for microglia in sculpting nervous system structure and function, as well as their important role in neuropathic pain, and finally integrate these studies to synthesize a new model for microglia in somatosensory circuit remodelling, composed of six key and inter-related mechanisms. Summarizing the mechanisms through which microglia modulate nervous system structure and function helps to frame a better understanding of neuropathic pain, and provide a clear roadmap for future research.
Stable isotopes of fatty acids: current and future perspectives for advancing trophic ecology
Authors: Twining Cornelia W. , Taipale Sami J. , Ruess Liliane , Bec Alexandre , Martin-Creuzburg Dominik , Kainz Martin J.
Published: June 2020

To understand consumer dietary requirements and resource use across ecosystems, researchers have employed a variety of methods, including bulk stable isotope and fatty acid composition analyses. Compound-specific stable isotope analysis (CSIA) of fatty acids combines both of these tools into an even more powerful method with the capacity to broaden our understanding of food web ecology and nutritional dynamics. Here, we provide an overview of the potential that CSIA studies hold and their constraints. We first review the use of fatty acid CSIA in ecology at the natural abundance level as well as enriched physiological tracers, and highlight the unique insights that CSIA of fatty acids can provide. Next, we evaluate methodological best practices when generating and interpreting CSIA data. We then introduce three cutting-edge methods: hydrogen CSIA of fatty acids, and fatty acid isotopomer and isotopologue analyses, which are not yet widely used in ecological studies, but hold the potential to address some of the limitations of current techniques. Finally, we address future priorities in the field of CSIA including: generating more data across a wider range of taxa; lowering costs and increasing laboratory availability; working across disciplinary and methodological boundaries; and combining approaches to answer macroevolutionary questions.

This article is part of the theme issue ‘The next horizons for lipids as ‘trophic biomarkers’: evidence and significance of consumer modification of dietary fatty acids’.
Inter- and intraspecific differences in rotifer fatty acid composition during acclimation to low-quality food
Authors: Schälicke Svenja , Heim Silvia , Martin-Creuzburg Dominik , Wacker Alexander
Published: June 2020

Biochemical food quality constraints affect the performance of consumers and mediate trait variation among and within consumer species. To assess inter- and intraspecific differences in fatty acid retention and conversion in freshwater rotifers, we provided four strains of two closely related rotifer species,

Brachionus calyciflorus
sensu

stricto and
Brachionus fernandoi
, with food algae differing in their fatty acid composition. The rotifers grazed for 5 days on either
Nannochloropsis limnetica
or
Monoraphidium minutum
, two food algae with distinct polyunsaturated fatty acid (PUFA) profiles, before the diets were switched to PUFA-free
Synechococcus elongatus
, which was provided for three more days. We found between- and within-species differences in rotifer fatty acid compositions on the respective food sources and, in particular, highly specific acclimation reactions to the PUFA-free diet. The different reactions indicate inter- but also intraspecific differences in physiological traits, such as PUFA retention, allocation and bioconversion capacities, within the genus
Brachionus
that are most likely accompanied by differences in their nutritional demands. Our data suggest that biochemical food quality constraints act differently on traits of closely related species and of strains of a particular species and thus might be involved in shaping ecological interactions and evolutionary processes.

This article is part of the theme issue ‘The next horizons for lipids as ‘trophic biomarkers': evidence and significance of consumer modification of dietary fatty acids'.