bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Mu-Opiate Receptor Gene Polymorphism rs1799971 (A118G) on the Antidepressant and Dissociation Responses in Esketamine Nasal Spray Clinical Trials
Authors: Saad Ziad , Hibar Derrek , Fedgchin Maggie , Popova Vanina , Furey Maura L , Singh Jaskaran B , Kolb Hartmuth , Drevets Wayne C , Chen Guang
Published: April 2020

Background

At ketamine and esketamine doses at which antidepressant doses are achieved, these agents are relatively selective, noncompetitive, N-methyl-D-aspartate receptor antagonists. However, at substantially higher doses, ketamine has shown mu-opioid receptor (MOR–gene symbol: OPRM1) agonist effects. Preliminary clinical studies showed conflicting results on whether naltrexone, a MOR antagonist, blocks the antidepressant action of ketamine. We examined drug-induced or endogenous MOR involvement in the antidepressant and dissociative responses to esketamine by assessing the effects of a functional single nucleotide polymorphism rs1799971 (A118G) of OPRM1, which is known to alter MOR agonist-mediated responses.

Methods

Participants with treatment-resistant depression from 2 phase III, double-blind, controlled trials of esketamine (or placebo) nasal spray plus an oral antidepressant were genotyped for rs1799971. Participants received the experimental agents twice weekly for 4 weeks. Antidepressant responses were rated using the change in Montgomery–Åsberg Depression Rating Scale (MADRS) score on days 2 and 28 post-dose initiation, and dissociative side effects were assessed using the Clinician-Administered Dissociative-States Scale at 40 minutes post-dose on days 1 and 25.

Results

In the esketamine + antidepressant arm, no significant genotype effect of single nucleotide polymorphism rs1799971 (A118G) on MADRS score reductions was detected on either day 2 or 28. By contrast, in the antidepressant + placebo arm, there was a significant genotype effect on MADRS score reductions on day 2 and a nonsignificant trend on day 28 towards an improvement in depression symptoms in G-allele carriers. No significant genotype effects on dissociative responses were detected.

Conclusions

Variation in rs1799971 (A118G) did not affect the antidepressant response to esketamine + antidepressant. Antidepressant response to antidepressant + placebo was increased in G-allele carriers, compatible with previous reports that release of endorphins/enkephalins may play a role in mediating placebo effect.

Trial Registration

NCT02417064 and NCT02418585; www.clinicaltrials.gov
Real Tropicalization and Analytification of Semialgebraic Sets
Authors: Jell Philipp , Scheiderer Claus , Yu Josephine
Published: April 2020

Let $K$ be a real closed field with a nontrivial non-archimedean absolute value. We study a refined version of the tropicalization map, which we call real tropicalization map, that takes into account the signs on $K$. We study images of semialgebraic subsets of $K^n$ under this map from a general point of view. For a semialgebraic set $S \subseteq K^n$ we define a space $S_r^{{\operatorname{an}}}$ called the real analytification, which we show to be homeomorphic to the inverse limit of all real tropicalizations of $S$. We prove a real analogue of the tropical fundamental theorem and show that the tropicalization of any semialgebraic set is described by tropicalization of finitely many inequalities, which are valid on the semialgebraic set. We also study the topological properties of real analytification and tropicalization. If $X$ is an algebraic variety, we show that $X_r^{{\operatorname{an}}}$ can be canonically embedded into the real spectrum $X_r$ of $X$, and we study its relation with the Berkovich analytification of $X$.
Incorporating home healthcare nurses’ admission information needs to inform data standards
Authors: Sockolow Paulina S , Bowles Kathryn H , Wojciechowicz Christine , Bass Ellen J
Published: April 2020

Objective

Patient transitions into home health care (HHC) often occur without the transfer of information needed for critical clinical decisions and the plan of care. Owing to a lack of universally implemented standards, there is wide variation in information transfer. We sought to characterize missing information at HHC admission.

Materials and Methods

We conducted a mixed methods study with 3 diverse HHC agencies. Focus groups with nurses at each agency identified what information supports patient care decisions at admission. Thirty-six in-home admissions with associated documentation review determined the available information. To inform information standards development for the HHC admission process, we compared the types of information desired and available to an international standard for transitions in care information, the Continuity of Care Document (CCD) enhanced with Office of the National Coordinator for Healthcare Information Technology summary terms (CCD/S).

Results

Three-quarters of the items from the focus groups mapped to the CCD/S. Regarding available information at admission, no observation included all CCD/S data items. While medication information was needed and often available for 4 important decisions, concepts related to patient medication self-management appeared in neither the CCD/S nor the admission documentation.

Discussion

The CCD/S mostly met HHC nurses’ information needs and is recommended to begin to fill the current information gap. Electronic health record recommendations include use of a data standard: the CCD or the proposed, more parsimonious U.S. Core Data for Interoperability.

Conclusions

Referral source and HHC agency adoption of data standards is recommended to support structured, consistent data and information sharing.
MINIMAR (MINimum Information for Medical AI Reporting): Developing reporting standards for artificial intelligence in health care
Authors: Hernandez-Boussard Tina , Bozkurt Selen , Ioannidis John P A , Shah Nigam H
Published: April 2020

The rise of digital data and computing power have contributed to significant advancements in artificial intelligence (AI), leading to the use of classification and prediction models in health care to enhance clinical decision-making for diagnosis, treatment and prognosis. However, such advances are limited by the lack of reporting standards for the data used to develop those models, the model architecture, and the model evaluation and validation processes. Here, we present MINIMAR (MINimum Information for Medical AI Reporting), a proposal describing the minimum information necessary to understand intended predictions, target populations, and hidden biases, and the ability to generalize these emerging technologies. We call for a standard to accurately and responsibly report on AI in health care. This will facilitate the design and implementation of these models and promote the development and use of associated clinical decision support tools, as well as manage concerns regarding accuracy and bias.
The Role of Cognitive Bias in Breast Radiology Diagnostic and Judgment Errors
Authors: Loving Vilert A , Valencia Elizabeth M , Patel Bhavika , Johnston Brian S
Published: April 2020

Cognitive bias is an unavoidable aspect of human decision-making. In breast radiology, these biases contribute to missed or erroneous diagnoses and mistaken judgments. This article introduces breast radiologists to eight cognitive biases commonly encountered in breast radiology: anchoring, availability, commission, confirmation, gambler’s fallacy, omission, satisfaction of search, and outcome. In addition to illustrative cases, this article offers suggestions for radiologists to better recognize and counteract these biases at the individual level and at the organizational level.
Aerial and aquatic respiration in littoral Oniscidea (Isopoda) from Southern California, USA
Authors: Wright Jonathan C , Harris Zechariah C
Published: April 2020

The large radiation of terrestrial isopods (suborder Oniscidea) includes several families that are represented primarily in marine-littoral or riparian habitats. Among these are members of Ligiidae and Tylidae as well as several basal families within the section Crinocheta. Structural and physiological evidence supports a marine-littoral ancestry of the Oniscidea. We examined aerial and aquatic respiration (measured as VCO2) in six species of marine-littoral Oniscidea representing five families, as well as one riparian and one endogean species. Complimentary data were collected for immersion tolerance and whole-animal permeability in air, and structural specialization of the respiratory pleopods was examined using SEM. Ligia occidentalis Dana, 1853 (marine, littoral) and Ligidium lapetum Mulaik & Mulaik, 1942 (riparian) showed similar VCO2 in air and water. VCO2 in air for the other species was significantly higher than in water. Compared across species, aerial VCO2 scaled with mass in accordance with Kleiber’s law (β = 0.774) while aquatic VCO2 increased in approximate proportion to mass (β = 0.957). At least some specimens of the six marine-littoral species survived over 24 h immersion. Ligidium lapetum and the endogean trichoniscid Brackenridgia heroldi (Arcangeli, 1932) also tolerated prolonged immersion in freshwater but did not survive beyond 5–6 h, probably due to limited capacity for hyper-regulation. The upper shore sand-burrowers, Tylos punctatus Holmes & Gay, 1909 and Alloniscus perconvexus Dana, 1856 had the lowest permeability among the study species and are the only representatives with elaborated pleopodal respiratory fields (Alloniscus) and lungs (Tylos). The ventral lung spiracles of T. punctatus are surrounded by an extensive cuticle meshwork and we propose that this functions as a plastron field to enhance aquatic gas exchange. Collectively, the results show that littoral species tolerate significant periods of immersion, allowing them to withstand habitat inundation during spring high tides, storm swells and, in riparian species, rainstorms and snowmelt.
Honey Bee Queen Production: Canadian Costing Case Study and Profitability Analysis
Authors: Bixby Miriam , Hoover Shelley E , McCallum Robyn , Ibrahim Abdullah , Ovinge Lynae , Olmstead Sawyer , Pernal Stephen F , Zayed Amro , Foster Leonard J , Guarna M Marta
Published: April 2020

The decline in managed honey bee (Hymenoptera: Apidae) colony health worldwide has had a significant impact on the beekeeping industry. To mitigate colony losses, beekeepers in Canada and around the world introduce queens into replacement colonies; however, Canada’s short queen rearing season has historically limited the production of early season queens. As a result, Canadian beekeepers rely on the importation of foreign bees, particularly queens from warmer climates. Importing a large proportion of (often mal-adapted) queens each year creates a dependency on foreign bee sources, putting beekeeping, and pollination sectors at risk in the event of border closures, transportation issues, and other restrictions as is currently happening due to the 2020 Covid-19 pandemic. Although traditional Canadian queen production is unable to fully meet early season demand, increasing domestic queen production to meet mid- and later season demand would reduce Canada’s dependency. As well, on-going studies exploring the potential for overwintering queens in Canada may offer a strategy to have early season domestic queens available. Increasing the local supply of queens could provide Canadian beekeepers, farmers, and consumers with a greater level of agricultural stability and food security. Our study is the first rigorous analysis of the economic feasibility of queen production. We present the costs of queen production for three Canadian operations over two years. Our results show that it can be profitable for a beekeeping operation in Canada to produce queen cells and mated queens and could be one viable strategy to increase the sustainability of the beekeeping industry.
Trapping White-Tailed Deer (Artiodactyla: Cervidae) in Suburbia for Study of Tick–Host Interaction
Authors: Roden-Reynolds Patrick , Machtinger Erika T , Li Andrew Y , Mullinax Jennifer M
Published: April 2020

Live capture of white-tailed deer (Odocoileus virginianus) (Zimmermann, 1780) is often necessary for research, population control, disease monitoring, and parasite surveillance. We provide our deer trapping protocol used in a tick-host vector ecology research project and recommendations to improve efficiency of deer trapping programs using drop nets in suburban areas. We captured 125 deer across two trapping seasons. Generally, lower daily minimum temperatures were related to increased capture probability, along with the presence of snow. Our most successful trapping sites were less forested, contained more fragmentation, and greater proportion of human development (buildings, roads, recreational fields). To improve future suburban deer trapping success, trapping efforts should include areas dominated by recreational fields and should not emphasize remote, heavily forested, less fragmented parks. Concurrently, our study illustrated the heterogeneous nature of tick distributions, and we collected most ticks from one trapping site with moderate parameter values between the extremes of the most developed and least developed trapping sites. This emphasized the need to distribute trapping sites to not only increase your capture success but to also trap in areas across varying levels of urbanization and fragmentation to increase the probability of parasite collection.
Factors associated with health-related quality of life in patients with glioma: impact of symptoms and implications for rehabilitation
Authors: Umezaki Shigeko , Shinoda Yusuke , Mukasa Akitake , Tanaka Shota , Takayanagi Shunsaku , Oka Hiroyuki , Tagawa Hisato , Haga Nobuhiko , Yoshino Mariko
Published: April 2020

Objective

The factors associated with health-related quality of life in patients with glioma remain unclear; particularly, the impact of symptoms on quality of life has not been studied comprehensively. This study aims to document the quality of life of patients with glioma and clarify the impact of symptoms.

Methods

In this cross-sectional study, participants were recruited from patients at The University of Tokyo Hospital and from patients who were registered at the Japan Brain Tumor Alliance. We included adult patients with World Health Organization grade II–IV glioma and excluded those with disturbances of consciousness or aphasia. We used the European Organization for Research and Treatment of Cancer QLQ-C30 and BN20 to evaluate quality of life and the symptoms. Multiple regression analyses were performed to investigate the impact of symptoms on European Organization for Research and Treatment of Cancer global health status and QLQ-C30 social functioning. In addition, we performed univariate subgroup analyses classified by World Health Organization grade and history of chemotherapy.

Results

This study included 76 patients. Seven symptoms occurred in more than 50% of the patients: fatigue, future uncertainty, drowsiness, communication deficit, financial difficulties, motor dysfunction and weakness of legs. Multiple regression analyses showed that insomnia affected their global health status, and appetite loss, financial difficulties and motor dysfunction were significantly related to their social functioning. In subgroup analysis, the number of symptom subscales that were significantly related to global health status and social functioning was larger in World Health Organization grade II patients compared with grade III/IV patients.

Conclusions

In addition to neurological deficits, symptoms were associated with poor quality of life in patients with glioma. This study provided the basis on further investigation of usefulness of symptom evaluation on quality of life improvement.
Spinocerebellar Ataxia Type 3: A Case Report and Literature Review
Authors: McCord Matthew R , Bigio Eileen H , Kam Kwok Ling , Fischer Victoria , Obeidin Farres , White Charles L , Brat Daniel J , Muller William A , Mao Qinwen
Published: April 2020

Spinocerebellar ataxia type 3 (SCA3), also known by the eponym Machado-Joseph disease, is an autosomal dominant CAG trinucleotide (polyglutamine) repeat disease that presents in young- to middle-aged adults. SCA3 was first described in Azorean individuals and has interesting epidemiological patterns. It is characterized clinically by progressive ataxia and neuropathologically by progressive degenerative changes in the spinal cord and cerebellum, along with degeneration of the cortex and basal ganglia. Here, we describe the clinical and neuropathologic features in a case of SCA3 with unique findings, including involvement of the inferior olivary nucleus and cerebellar Purkinje cell layer, which are classically spared in the disease. We also discuss research into the disease mechanisms of SCA3 and the potential for therapeutic intervention.
50 Studies Every Ophthalmologist Should Know
Authors: Penman Alan , Crowder Kimberley , Watkins William M.
Published: April 2020

50 Studies Every Ophthalmologist Should Know succinctly summarizes the most important and clinically relevant studies published in the mainstream ophthalmology literature in the past forty years. Emphasis has been placed on landmark studies, that changed thinking and practice in the field, rather than studies that are most frequently cited. Most are randomized controlled trials that have helped shape current ophthalmology practice guidelines. However, some important observational (cohort, case-control, and descriptive) studies are also included. The book is divided into seven sections, corresponding to anatomical segment or disease of the eye (cornea, cataract, glaucoma, vitreoretinal, macula, uveal tract, and orbit/eyelids/extraocular muscles/optic nerve). Each chapter finishes with an illustrative clinical case, and includes a reference to the relevant section of the practice guidelines of the American Academy of Ophthalmology.
The book is not aimed solely at ophthalmologists, however. Every practicing physician, no matter his or her specialty, should be familiar with the relation of the eye to the rest of the human body, and with the use and value of the ophthalmoscope. Ophthalmology has a particular relevance to physicians working in primary care, internal medicine, neurology, neurosurgery, pediatrics, and emergency medicine.
Whose Decision Is This?
Authors: Miller Elissa G.
Published: April 2020

Decision-making in palliative and end-of-life care can be difficult to navigate. This is even more so in pediatric palliative and end of life care when parents may disagree with each other or for teenagers who are not yet legally able to make their own medical decisions. Surrogate decision making can also complicate end of life decision making in pediatrics. To navigate these complex situations, the best interest standard, harm principle, and other standards are often applied when concerns arise over surrogate decision-making. This chapter presents a discussion of the ethical principles and a recommended approach to managing clinical situations with uncertain or conflicting surrogate decision-makers.
Is She Dying?
Authors: Miller Elissa G.
Published: April 2020

Patient prognosis at or near end of life may be very important to families who are trying to gauge how much time they have left with their dying child. Answering families’ questions regarding their child’s prognosis honestly while leaving room for uncertainty is important. Physical signs and symptoms of dying may be helpful in determining prognosis at the very end of life. Families may also want to know what signs and symptoms to expect as their child is dying. This chapter discusses care of the actively dying child, including physical changes, medication management, and helping patients be comfortable in the location of the family’s choosing.
My Skin Feels Like It Is on Fire
Authors: Ragsdale Lindsay B.
Published: April 2020

Neuropathic pain can be a source of significant distress and can greatly impact patients’ quality of life. Although neuropathic pain is not well understood and evidence is lacking in pediatrics, there are strategies to improve symptom burden and improve quality of life in patients with neuropathic pain. Diagnosis and assessment of neuropathic pain should follow similar assessments for somatic pain with the addition of specific questions to help further delineate neuropathic pain. Most neuropathic assessment tools explore the patient’s feeling of prickling, tingling, pins and needles, shock or shooting, hot or burning, numbness, and allodynia, but none are currently validated in pediatrics. Treatment strategies can include treating the underlying disease process when possible, systemic medications, topical medications, integrative techniques, and interventional nerve blocks.
My Patient Is Twitching; Could It Be Itching?
Authors: Morvant Alexis , Jones Emma
Published: April 2020

Pediatric patients receiving palliative care may experience itching as a distressing symptom for a wide variety of reasons. Antihistamine medications are widely used for treatment of this symptom and have effectiveness if histamine is the primary mechanism of itch. Pruritus is a known adverse effect of opioid therapy, occurring in 2–10% of patients. Opioid-induced pruritus is not primarily histamine related and therefore better treated by partial opioid antagonists. Chronic health conditions such as renal disease, cholestasis, and malignancy are all associated with pruritus. This chapter presents a broad differential for the symptom as well as a range of pharmacologic and nonpharmacologic therapies.
I Feel My Baby Moving; How Is She Incompatible with Life?
Authors: Ragsdale Lindsay B.
Published: April 2020

The diagnosis of trisomy 13 or 18 can be devastating to expectant parents. Historical data indicate that many infants did not survive past a few days of life. However, recent data indicate a longer survival rate, especially with medical interventions. More centers are offering surgical interventions for congenital heart disease, intestinal dysfunction, apnea, and brain abnormalities. Few studies have shown the long-term implications of more intensive medical care on quality of life for older children with these syndromes. Attention should be given to issues of suffering and quality of life over time for these children. Medical teams should explore family goals and strive to align medical care with these values.
A Moment Becomes a Memory
Authors: Ragsdale Lindsay B.
Published: April 2020

Anencephaly is a lethal neural tube defect that results in the absence of skull and scalp with only remnants of brain and brain stem remaining at birth. Although there is a high risk for intrauterine fetal demise and stillbirth, neonates affected by anencephaly can be born alive and may live for hours to days. There is no cure or treatment for anencephaly; however, symptom management, end-of-life care, and family support should be offered. Some families may find it difficult to see the exposed brain; acknowledging this challenge and using bonnets and coverings can help ease this discomfort. Organ donation for transplant is not currently an option for infants with anencephaly, but tissue donation and research donations are potential options in some areas. There is a wide spectrum of severity and survival in other brain abnormalities; each case should be evaluated individually, and palliative programs should strive to align care with family goals.
Why Is She So Distressed?
Authors: Webb Daniel Waechter , Thorvilson Megan J.
Published: April 2020

Illness often raises many questions related to humanity and life meaning both for children and their families, and many lean on spirituality to sustain them in difficult times. When one’s ability to experience and integrate meaning in life becomes disrupted, patients may experience spiritual distress, which can present in physical, psychological, and social ways. The majority of pediatricians acknowledge a positive role for spirituality in healing, in strengthening the therapeutic relationship, and in providing support for patients/families, yet clinicians often feel ill-equipped to address spirituality with families. However, most parents would prefer to be open about their spiritual beliefs and practices with their medical team. In addition to the clinician, chaplains, child life specialists, social workers, and psychologists can support the evolving spiritual needs of children as they grow and develop.
Person with Epilepsy, Doctor, and Advocate
Authors: Smith Brien
Published: April 2020

The pursuit of medical careers, as well as advocating for epilepsy research, ketogenic therapies, and neuro-rehabilitation are among the efforts in this section on healthcare and research.
One Family at a Time
Authors: Koh Sookyong
Published: April 2020

The pursuit of medical careers, as well as advocating for epilepsy research, ketogenic therapies, and neuro-rehabilitation are among the efforts in this section on healthcare and research.
Making a Difference
Authors: Kelly Laurie
Published: April 2020

Furthering the missions of epilepsy organizations, by either volunteering for, starting, or running an organization that serves people with epilepsy have been the goals of the advocates who have dedicated their lives to organizational advocacy.
My Path to Advocacy
Authors: McGrath Deb
Published: April 2020

Furthering the missions of epilepsy organizations, by either volunteering for, starting, or running an organization that serves people with epilepsy have been the goals of the advocates who have dedicated their lives to organizational advocacy.
Family, Advocacy, and Tracking Seizures
Authors: Moss Rob , Moss Lisa
Published: April 2020

In this section, people’s experiences with rare forms of epilepsy have given rise to many forms of advocacy for people with epilepsy. From forming an organization to tracking seizures, there is no act of advocacy too large or small.
Advocacy Takes Many Forms
Authors: Swoyer Barbara
Published: April 2020

In this section, people’s experiences with rare forms of epilepsy have given rise to many forms of advocacy for people with epilepsy. From forming an organization to tracking seizures, there is no act of advocacy too large or small.
Hope for Many
Authors: Miller Ilene
Published: April 2020

In this section, people’s experiences with rare forms of epilepsy have given rise to many forms of advocacy for people with epilepsy. From forming an organization to tracking seizures, there is no act of advocacy too large or small.
Strength, Epilepsy, and Advocacy
Authors: Gunn Chanda
Published: April 2020

An elite athlete using her platform for epilepsy awareness, a person with epilepsy who climbed his way to a better life, and a man who ran a marathon backwards to raise funds and awareness of epilepsy are part of the journeys of the advocates in this section.
Telling Christopher’s Story
Authors: Donalty Jeanne
Published: April 2020

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in people with uncontrolled seizures. This section details the lives of people who have lost a loved one to SUDEP and found meaning from their tragedies by helping others in similar situations.
Change, Meaning, and Purpose
Authors: Coughlin-Brooks Linda
Published: April 2020

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in people with uncontrolled seizures. This section details the lives of people who have lost a loved one to SUDEP and found meaning from their tragedies by helping others in similar situations.
Chelsea’s Circle
Authors: Hutchison Julie L.
Published: April 2020

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in people with uncontrolled seizures. This section details the lives of people who have lost a loved one to SUDEP and found meaning from their tragedies by helping others in similar situations.
Differences and similarities of stellar populations in LAEs and LBGs at z ∼ 3.4−6.8
Authors: Arrabal Haro P , Rodríguez Espinosa J M , Muñoz-Tuñón C , Sobral D , Lumbreras-Calle A , Boquien M , Hernán-Caballero A , Rodríguez-Muñoz L , Alcalde Pampliega B
Published: April 2020

Lyman alpha emitters (LAEs) and Lyman break galaxies (LBGs) represent the most common groups of star-forming galaxies at high z, and the differences between their inherent stellar populations (SPs) are a key factor in understanding early galaxy formation and evolution. We have run a set of SP burst-like models for a sample of 1558 sources at 3.4 < z < 6.8 from the Survey for High-z Absorption Red and Dead Sources (SHARDS) over the GOODS-N field. This work focuses on the differences between the three different observational subfamilies of our sample: LAE–LBGs, no-Ly α LBGs, and pure LAEs. Single and double SP synthetic spectra were used to model the spectral energy distributions, adopting a Bayesian information criterion to analyze under which situations a second SP is required. We find that the sources are well modelled using a single SP in $\sim 79{{\ \rm per\ cent}}$ of the cases. The best models suggest that pure LAEs are typically young low-mass galaxies ($t\sim 26^{+41}_{-25}$ Myr; $M_{\mathrm{star}}\sim 5.6^{+12.0}_{-5.5}\times 10^{8}\ M_{\odot }$), undergoing one of their first bursts of star formation. On the other hand, no-Ly α LBGs require older SPs (t ∼ 71 ± 12 Myr), and they are substantially more massive (Mstar ∼ 3.5 ± 1.1 × 109 M⊙). LAE–LBGs appear as the subgroup that more frequently needs the addition of a second SP, representing an old and massive galaxy caught in a strong recent star-forming episode. The relative number of sources found from each subfamily at each z supports an evolutionary scenario from pure LAEs and single SP LAE–LBGs to more massive LBGs. Stellar mass functions are also derived, finding an increase of M* with cosmic time and a possible steepening of the low-mass slope from z ∼ 6 to z ∼ 5 with no significant change to z ∼ 4. Additionally, we have derived the SFR–Mstar relation, finding an $\mathrm{SFR}\propto M_{\mathrm{star}}^{\beta }$ behaviour with negligible evolution from z ∼ 4 to z ∼ 6.
The heavier the better: how to constrain mass ratios and spins of high-mass neutron star mergers
Authors: Most Elias R , Weih Lukas R , Rezzolla Luciano
Published: April 2020

The first binary neutron star merger event, GW170817, and its bright electromagnetic counterpart have provided a remarkable amount of information. By contrast, the second event, GW190425, with $M_{\rm tot}=3.4^{+0.3}_{-0.1}\, \mathrm{ M}_{\odot }$ and the lack of an electromagnetic counterpart, has hardly improved our understanding of neutron star physics. While GW190425 is compatible with a scenario in which the merger has led to a prompt collapse to a black hole and little ejected matter to power a counterpart, determining the mass ratio and the effective spin $\tilde{\chi }$ of the binary remains difficult. This is because gravitational waveforms cannot yet well constrain the component spins of the binary. However, since the mass of GW190425 is significantly larger than the maximum mass for non-rotating neutron stars, $M_{_{\rm TOV}}$, the mass ratio q cannot be too small, as the heavier star would not be gravitationally stable. Making use of universal relations and a large number of equations of state, we provide limits in the $(\tilde{\chi },q)$ plane for GW190425, namely qmin ≥ 0.38 and $\tilde{\chi }_{\rm max}\le 0.20$, assuming $M_\mathrm{tot} \simeq 3.4\, \mathrm{ M}_\odot$. Finally, we show how future observations of high-mass binaries can provide a lower bound on $M_{_{\rm TOV}}$.
Histone variant H2A.Z regulates nucleosome unwrapping and CTCF binding in mouse ES cells
Authors: Wen Zengqi , Zhang Liwei , Ruan Haihe , Li Guohong
Published: April 2020

Nucleosome is the basic structural unit of chromatin, and its dynamics plays critical roles in the regulation of genome functions. However, how the nucleosome structure is regulated by histone variants in vivo is still largely uncharacterized. Here, by employing Micrococcal nuclease (MNase) digestion of crosslinked chromatin followed by chromatin immunoprecipitation (ChIP) and paired-end sequencing (MNase-X-ChIP-seq), we mapped unwrapping states of nucleosomes containing histone variant H2A.Z in mouse embryonic stem (ES) cells. We found that H2A.Z nucleosomes are more enriched with unwrapping states compared with canonical nucleosomes. Interestingly, +1 H2A.Z nucleosomes with 30–80 bp DNA is correlated with less active genes compared with +1 H2A.Z nucleosomes with 120–140 bp DNA. We confirmed the unwrapping of H2A.Z nucleosomes under native condition by re-ChIP of H2A.Z and H2A after CTCF CUT&RUN in mouse ES cells. Importantly, we found that depletion of H2A.Z results in decreased unwrapping of H3.3 nucleosomes and increased CTCF binding. Taken together, through MNase-X-ChIP-seq, we showed that histone variant H2A.Z regulates nucleosome unwrapping in vivo and that its function in regulating transcription or CTCF binding is correlated with unwrapping states of H2A.Z nucleosomes.
AnnoLnc2: the one-stop portal to systematically annotate novel lncRNAs for human and mouse
Authors: Ke Lan , Yang De-Chang , Wang Yu , Ding Yang , Gao Ge
Published: April 2020

With the abundant mammalian lncRNAs identified recently, a comprehensive annotation resource for these novel lncRNAs is an urgent need. Since its first release in November 2016, AnnoLnc has been the only online server for comprehensively annotating novel human lncRNAs on-the-fly. Here, with significant updates to multiple annotation modules, backend datasets and the code base, AnnoLnc2 continues the effort to provide the scientific community with a one-stop online portal for systematically annotating novel human and mouse lncRNAs with a comprehensive functional spectrum covering sequences, structure, expression, regulation, genetic association and evolution. In response to numerous requests from multiple users, a standalone package is also provided for large-scale offline analysis. We believe that updated AnnoLnc2 (http://annolnc.gao-lab.org/) will help both computational and bench biologists identify lncRNA functions and investigate underlying mechanisms.
Immunogenicity and Reactogenicity of a Reduced Schedule of a 4-component Capsular Group B Meningococcal Vaccine: A Randomized Controlled Trial in Infants
Authors: Valente Pinto Marta , O’Connor Daniel , Galal Ushma , Clutterbuck Elizabeth A , Robinson Hannah , Plested Emma , Bibi Sagida , Camara Pellisso Susana , Hughes Harri , Kerridge Simon , Mujadidi Yama F , Findlow Helen , Borrow Ray , Snape Matthew D , Pollard Andrew J
Published: April 2020

Background

The 4-component capsular group B meningococcal vaccine (4CMenB) was licensed as a 4-dose infant schedule but introduced into the United Kingdom as 3 doses at 2, 4, and 12 months of age. We describe the immunogenicity and reactogenicity of the 2 + 1 schedule in infants.

Methods

Infants were randomized to receive 4CMenB with routine immunizations (test group) at 2, 4, and 12 months or 4CMenB alone at 6, 8, and 13 months of age (control group). Serum bactericidal antibody (SBA) assay against a serogroup B meningococcal reference strain (44/76-SL), memory B-cell responses to factor H binding protein, Neisseria adhesion protein A, Neisseria heparin binding antigen, Porin A (PorA), and reactogenicity was measured.

Results

One hundred eighty-seven infants were randomized (test group: 94; control group: 93). In the test group, 4CMenB induced SBA titers above the putative protective threshold (1:4) after primary and booster doses in 97% of participants. Postbooster, the SBA GMT (72.1; 95% confidence interval [CI], 51.7–100.4) was numerically higher than the serum bactericidal antibody geometric mean titre (SBA GMT) determined post–primary vaccination (48.6; 95% CI, 37.2–63.4).

After primary immunizations, memory B-cell responses did not change when compared with baseline controls, but frequencies significantly increased after booster. Higher frequency of local and systemic adverse reactions was associated with 4CMenB.

Conclusions

A reduced schedule of 4CMenB was immunogenic and established immunological memory after booster.
Endoscopic Fenestration of Cavum Septum Pellucidum Cysts to the Third Ventricle: Technical Note
Authors: Simonin Alexandre , Bangash Omar , Chandran Arjun S , Uvelius Erik , Lind Christopher
Published: April 2020

BACKGROUND AND IMPORTANCE

Cavum septum pellucidum (CSP) and cavum vergae (CV) cysts are common incidental findings on imaging studies. However, they may rarely present with symptoms related to the obstruction of the foramen of Monro by the cyst leaflets. There is no consensus regarding the management of symptomatic CSP and CV cysts. We present an original transcavum interforniceal endoscopic fenestration technique. The step-by-step surgical procedure and two illustrative cases are presented.

CLINICAL PRESENTATION

A 31-yr-old male and a 24-yr-old woman presented with symptomatic CSP and CV cysts. For both patients, neuronavigation was used to plan the procedure. An endoscope was introduced into the cyst through a right frontal burr-hole. After an examination of the endoscopic anatomy, a communication between the cyst and the third ventricle was performed using an endoscopic forceps. In both cases, directly after the fenestration, cerebrospinal fluid (CSF) passed through the communication, and the collapse of the cyst was appreciated. Symptoms were relieved in both patients, and neuropsychological assessment improved. Postoperative imaging showed a reduction in the cyst bulge, and patent foramen of Monro.

CONCLUSION

Endoscopic fenestration of CSP and CV cysts to the third ventricle through an interforniceal navigated approach is a feasible and efficient surgical procedure. Theoretical advantages include a single tract through noneloquent brain, a perpendicular trajectory to the membrane for fenestration, and a large CSF space beyond the fenestration point.
In vitro evolution of phi29 DNA polymerases through compartmentalized gene expression and rolling-circle replication
Authors: Sakatani Yoshihiro , Mizuuchi Ryo , Ichihashi Norikazu
Published: April 2020

Phi29 DNA polymerase is widely used for DNA amplification through rolling-circle replication or multiple displacement amplification. Here, we performed completely in vitro artificial evolution of phi29 DNA polymerase by combining the in vitro compartmentalization and the gene expression-coupled rolling-circle replication of a circular DNA encoding the polymerase. We conducted the experiments in six different conditions composed of three different levels of inhibitor concentrations with two different DNA labeling methods. One of the experiments was performed in our previous study and the other five experiments were newly conducted in this study. Under all conditions, we found several mutations that enhance the rolling-circle amplification by the polymerase when it was expressed in the reconstituted gene expression system. Especially, a combinatorial mutant polymerase (K555T/D570N) exhibits significantly higher rolling-circle activity than the wild type. These highly active mutant polymerases would be useful for various applications.
Digital phenotyping of negative symptoms: the relationship to clinician ratings
Authors: Cohen Alex S , Schwartz Elana , Le Thanh P , Cowan Tovah , Kirkpatrick Brian , Raugh Ian M , Strauss Gregory P
Published: April 2020

Negative symptoms are a critical, but poorly understood, aspect of schizophrenia. Measurement of negative symptoms primarily relies on clinician ratings, an endeavor with established reliability and validity. There have been increasing attempts to digitally phenotype negative symptoms using objective biobehavioral technologies, eg, using computerized analysis of vocal, speech, facial, hand and other behaviors. Surprisingly, biobehavioral technologies and clinician ratings are only modestly inter-related, and findings from individual studies often do not replicate or are counterintuitive. In this article, we document and evaluate this lack of convergence in 4 case studies, in an archival dataset of 877 audio/video samples, and in the extant literature. We then explain this divergence in terms of “resolution”—a critical psychometric property in biomedical, engineering, and computational sciences defined as precision in distinguishing various aspects of a signal. We demonstrate how convergence between clinical ratings and biobehavioral data can be achieved by scaling data across various resolutions. Clinical ratings reflect an indispensable tool that integrates considerable information into actionable, yet “low resolution” ordinal ratings. This allows viewing of the “forest” of negative symptoms. Unfortunately, their resolution cannot be scaled or decomposed with sufficient precision to isolate the time, setting, and nature of negative symptoms for many purposes (ie, to see the “trees”). Biobehavioral measures afford precision for understanding when, where, and why negative symptoms emerge, though much work is needed to validate them. Digital phenotyping of negative symptoms can provide unprecedented opportunities for tracking, understanding, and treating them, but requires consideration of resolution.
Decolonizing Global Health Education: Rethinking Institutional Partnerships and Approaches
Authors: Eichbaum Quentin G. , Adams Lisa V. , Evert Jessica , Ho Ming-Jung , Semali Innocent A. , van Schalkwyk Susan C.
Published: April 2020

Global health often entails partnerships between institutions in low- and middle-income countries (LMICs) that were previously colonized and high-income countries (HICs) that were colonizers. Little attention has been paid to the legacy of former colonial relationships and the influence they have on global health initiatives. There have been recent calls for the decolonization of global health education and the reexamination of assumptions and practices under pinning global health partnerships.

Medicine’s role in colonialism cannot be ignored and requires critical review. There is a growing awareness of how knowledge generated in HICs defines practices and informs thinking to the detriment of knowledge systems in LMICs. Additionally, research partnerships often benefit the better-resourced partner.

In this article, the authors offer a brief analysis of the intersections between colonialism, medicine, and global health education and explore the lingering impact of colonialist legacies on current global health programs and partnerships. They describe how “decolonized” perspectives have not gained sufficient traction and how inequitable power dynamics and neocolonialist assumptions continue to dominate. They discuss 5 approaches, and highlight resources, that challenge colonial paradigms in the global health arena. Furthermore, they argue for the inclusion of more transfor mative learning approaches to promote change in attitudes and practice. They call for critical reflection and concomitant action to shift colonial paradigms toward more equitable partnerships in global education.
The Transition From Medical Student to Resident: A Qualitative Study of New Residents’ Perspectives
Authors: Chang Lucy Y. , Eliasz Kinga L. , Cacciatore Danielle T. , Winkel Abigail Ford
Published: April 2020

Purpose

To understand the learner’s perspective on the transition from medical school to residency and to develop a conceptual model for how learners experience the transition from student to resident.

Method

This prospective qualitative study explored the experience of first-year residents using semistructured, one-on-one telephone interviews. Ten first-year residents who participated in the Transition to Residency elective as fourth-year students at the New York University Grossman School of Medicine in April 2018 participated from December 2018 to April 2019. Using a 3-phase coding process and grounded theory methodology, the authors identified categories, which they organized into broader themes across interview transcripts and used to develop a conceptual model.

Results

From the perspective of new residents, developing professional identity is the core construct of the transition experience. The residents focused on individual aspects of the experience—professional identity, self-awareness, professional growth, approach to learning, and personal balance—and external aspects—context of learning, professional relationships, and challenges in the context of their new role. Across these 8 categories, 5 broader themes emerged to describe an abrupt change in educational environment, an immersive experience of learning as a resident, ambivalence and tensions around the new role, navigation of professional relationships, and balance and integration of working in medicine with personal lives and goals. A conceptual model illustrates this phenomenon as a cell where professional identity and growth (the nucleus) is surrounded by interactions with patients and other members of the medical team (in the cytoplasm) that create a substrate for learning and development.

Conclusions

This study suggests that being immersed in the residency experience is how medical students transition to resident physicians. Educational interventions that allow learners to acclimate to the experience of being a doctor through gradual exposure to authentic interactions have the potential to bridge the abrupt transition.
Association between Use of Angiotensin-converting Enzyme Inhibitors or Angiotensin Receptor Blockers and Postoperative Delirium
Authors: Farag Ehab , Liang Chen , Mascha Edward J. , Argalious Maged Y. , Ezell Jacob , Maheshwari Kamal , Esa Wael Ali Sakr , Troianos Christopher A. , Sessler Daniel I.
Published: April 2020

Background

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers improve cognitive function. The authors therefore tested the primary hypothesis that preoperative use of angiotensin inhibitors is associated with less delirium in critical care patients. Post hoc, the association between postoperative use of angiotensin system inhibitors and delirium was assessed.

Methods

The authors conducted a single-site cohort study of adults admitted to Cleveland Clinic critical care units after noncardiac procedures between 2013 and 2018 who had at least one Confusion Assessment Method delirium assessment. Patients with preexisting dementia, Alzheimer’s disease or other cognitive decline, and patients who had neurosurgical procedures were excluded. For the primary analysis, the confounder-adjusted association between preoperative angiotensin inhibitor use and the incidence of postoperative delirium was assessed. Post hoc, the confounder-adjusted association between postoperative angiotensin system inhibitor use and the incidence of delirium was assessed.

Results

The incidence of delirium was 39% (551 of 1,396) among patients who were treated preoperatively with angiotensin system inhibitors and 39% (1,344 of 3,468) in patients who were not. The adjusted odds ratio of experiencing delirium during critical care was 0.98 (95% CI, 0.86 to 1.10; P = 0.700) for preoperative use of angiotensin system inhibitors versus control. Delirium was observed in 23% (100 of 440) of patients who used angiotensin system inhibitors postoperatively before intensive care discharge, and in 41% (1,795 of 4,424) of patients who did not (unadjusted P < 0.001). The confounder-adjusted odds ratio for experiencing delirium in patients who used angiotensin system inhibitors postoperatively was 0.55 (95% CI, 0.43 to 0.72; P < 0.001).

Conclusions

Preoperative use of angiotensin system inhibitors is not associated with reduced postoperative delirium. In contrast, treatment during intensive care was associated with lower odds of delirium. Randomized trials of postoperative angiotensin-converting enzymes inhibitors and angiotensin receptor blockers seem justified.

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Early Acute Respiratory Support for Pregnant Patients With Coronavirus Disease 2019 (COVID-19) Infection
Authors: Pacheco Luis D. , Saad Antonio F. , Saade George
Published: April 2020

The present coronavirus disease 2019 (COVID-19) pandemic is affecting pregnant patients worldwide. Although it appears that the severity of disease is reduced in pregnant patients, some are likely to develop severe disease. Our objective is to summarize the basic initial respiratory support interventions recommended for pregnant patients with infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).