bluuebunny/crossref_metadata_2025 huggingface dataset:
A Boolean OR gate implemented with an optoelectronic switching memristor
Authors: Zhao Jianhui , Zhou Zhenyu , Wang Hong , Wang Jingjuan , Hao Weichang , Ren Deliang , Guo Rui , Chen Jingsheng , Liu Baoting , Yan Xiaobing
Published: October 2019

Nonvolatile stateful logic computing in memristors has tremendous potential to realize the aggregation combined with information storage and processing in the same physical location for breaking the von Neumann bottleneck of traditional computing architecture. Here, we fabricate a monoclinic BiVO4 film with a bandgap of Eg ≈ 2.4 eV and a nanoporous morphology as the memristor storage medium. The device, consisting of a TiN/BiVO4/fluorine-doped tin oxide structure, demonstrated excellent electric- and light-control of resistive switching performance. A Boolean “OR” gate is shown to be operable with an electrical signal and light signal as inputs and the resistance as output. According to the I–V fitting results, the conduction mechanism of the memristor is inferred to be trapped-assisted tunneling model. The large photocurrent is due to trapped electrons in the defects which will be released to the conduction band. The nanoporous structure and suitable bandgap are also beneficial to light absorption and electron detrapping for enlarging photocurrent. This work lays the device foundation for electrical–optical controlling logic functions in memristor devices.
Six-dimensional potential energy surfaces for the dissociative chemisorption of HCl on rigid Ag(100) and Ag(110) surfaces
Authors: Liu Tianhui , Fu Bina , Zhang Dong H.
Published: October 2019

The dependence of reactivity on different facets of a surface is an interesting subject in dynamics at gas-surface interfaces. Here, we constructed new six-dimensional (6D) potential energy surfaces (PESs) for the dissociative chemisorption of HCl on rigid Ag(100) and Ag(110) surfaces, using the neural network method based on extensive density functional theory (DFT) calculations with the Perdew-Burke-Ernzerhof (PBE) functional, and compared the two PESs with the previously fitted PES of HCl/Ag(111). Time-dependent wave packet calculations show that the new PESs are very well converged with respect to the fitting procedure as well as to the number of DFT data points. The 6D dissociation probabilities for HCl initially in the ground rovibrational state decrease gradually for HCl/Ag(110), HCl/Ag(100), and HCl/Ag(111), consistent with the increasing barrier heights for the three reactions. The validity of the site-averaging approximation for HCl/Ag(110) does not hold well as compared with HCl/Ag(100) and HCl/Ag(111), in particular, at low kinetic energies, due to the strong steering effect this reaction exhibits if it is modeled with the semilocal PBE functional, which results in a low reaction barrier and a deep physisorption well.
Identity for Kullback-Leibler divergence in density functional reactivity theory
Authors: Liu Shubin
Published: October 2019

Density functional reactivity theory (DFRT) makes use of simple electron density functionals to appreciate chemical reactivity. The Kullback-Leibler divergence, also called information gain or relative Shannon entropy, as a key component of the DFRT framework has entertained a few fascinating applications in the recent literature. For instance, it was employed to rationalize the Hirshfeld stockholder partition of atoms in molecules. It has also been applied to both determine regioselectivity and simultaneously quantify molecular electrophilicity and nucleophilicity, the capability of atoms in molecules to accept and donate electrons. In this work, we examine the local behavior of the Kullback-Leibler divergence and present a novel identity for it. The validity of the identity is subsequently verified by the numerical results of neutral atoms from He to Kr with different choices of the reference density. Analytical properties and local behaviors of the three new functions introduced in the identity are discussed. These new local functions, together with the identity unveiled in this work, should provide new perspectives for us to further develop the DFRT framework with added insights about the local behavior of molecular physiochemical properties.
Effects of larval diet quality on the growth and development of immature stages of Telostylinus angusticollis (Diptera : Neriidae)
Authors: Hooper Amy K. , Bonduriansky Russell
Published: October 2019

Nutrient abundance during development has profound effects on adult morphology, life history and behaviour in many insects, but effects of nutrition on juvenile development are less well known. We investigated how larval diet quality affects patterns of growth, development and survival of larvae and pupae in the neriid fly Telostylinus angusticollis (Enderlein). We reared flies on two larval diets varying in nutrient concentration (‘rich’ versus ‘poor’) that have been shown previously to affect a wide range of adult traits in this species. We found that nutrient concentration affected larval growth trajectories, with individuals reared on the rich diet exhibiting greatly accelerated growth and reaching a larger body size. By contrast, we found no evidence that diet affected timing of development at the pupal stage, suggesting that developmental constraints may prevent variation in pupal development rate. Although overall mortality during the immature stages was not affected by larval diet, we found some evidence that individuals reared on a poor diet might experience higher larval mortality, whereas individuals reared on a rich diet might experience higher mortality during emergence from the puparium. Our results enhance understanding of the effects of nutrition on growth, development, and life history.
A 2-dimensional ratchet model describes assembly initiation of a specialized bacterial cell surface
Authors: Peluso Emily A. , Updegrove Taylor B. , Chen Jiji , Shroff Hari , Ramamurthi Kumaran S.
Published: October 2019

Significance

The assembly of localized static structures is a culminating feature of developmental programs. Construction of the spore coat, a shell that surrounds bacterial spores, is a model for understanding how proteins localize and assemble at the correct place and time during morphogenesis. Using data derived from in vivo and in vitro single-molecule imaging, we propose a computational model in which coat assembly initiates via an interplay between 2 proteins: a protein that localizes preferentially to micron-scale convex membranes (the surface of the developing spore) and a recruited structural protein that polymerizes to hold the first protein in place. This ratchet model therefore describes how a static structure can be built specifically atop the 2-dimensional surface of a developing organelle.
Effect of rare earth elements on plasma electrolytic carbonitriding of Ti–6Al–4V alloy
Authors: Chen Feifei , Yu Shouxin , Lu Wenzhuang , Pang Jing , Tian Wanshan , Sun Yuli , Zuo Dunwen
Published: October 2019

The paper aims to research the effect of rare earth elements on the carbonitriding layer of titanium alloy by establishing a theoretical model between rare earth concentration and atomic diffusion efficiency. It shows that adding rare earth can not only refine the discharge holes, but also reduce surface cracks, which significantly improve the surface quality of the strengthening layer. It is also found that an appropriate amount of rare earth can greatly increase the growth rate of the carbonitriding layer and carbon content near the surface. Furthermore, compared with the conventional plasma electrolytic carbonitriding treatment, adding 2 g L−1 cerium oxide can effectively reduce the activation energy of carbon, so as to improve its diffusion ability.
Progressive recruitment of distal MEC-4 channels determines touch response strength in C. elegans
Authors: Katta Samata , Sanzeni Alessandro , Das Alakananda , Vergassola Massimo , Goodman Miriam B.
Published: October 2019

Touch deforms, or strains, the skin beyond the immediate point of contact. The spatiotemporal nature of the touch-induced strain fields depend on the mechanical properties of the skin and the tissues below. Somatosensory neurons that sense touch branch out within the skin and rely on a set of mechano-electrical transduction channels distributed within their dendrites to detect mechanical stimuli. Here, we sought to understand how tissue mechanics shape touch-induced mechanical strain across the skin over time and how individual channels located in different regions of the strain field contribute to the overall touch response. We leveraged Caenorhabditis elegans’ touch receptor neurons as a simple model amenable to in vivo whole-cell patch-clamp recording and an integrated experimental-computational approach to dissect the mechanisms underlying the spatial and temporal dynamics we observed. Consistent with the idea that strain is produced at a distance, we show that delivering strong stimuli outside the anatomical extent of the neuron is sufficient to evoke MRCs. The amplitude and kinetics of the MRCs depended on both stimulus displacement and speed. Finally, we found that the main factor responsible for touch sensitivity is the recruitment of progressively more distant channels by stronger stimuli, rather than modulation of channel open probability. This principle may generalize to somatosensory neurons with more complex morphologies.
Traversable Lorentzian wormholes in higher dimensional theories of gravity
Authors: Baruah Anshuman , Deshamukhya Atri
Published: October 2019

Wormhole solutions in classical general relativity are unstable and hence non traversable. Morris and Thorne discovered a traversable wormhole solution that required the energy momentum tensor of matter sources to violate various energy conditions and are out of the purview of the standard model of particle physics. The search for traversable wormhole solutions in modified theories of gravity has been of significant interest in the decades after Morris and Thorne first published their results as such violations may be avoided in such theories. This work comprehensively reviews traversable wormhole solutions in higher dimensional extensions of general relativity that satisfy the various energy conditions with an in depth look at the matter sources and the various constraints on the parameters of the theories to make the energy momentum of the matter sources respect the energy conditions.
“The Myth Is Dead! Give Us Our History!” Reassessing Black Labor in African HistoryThe Moon Is Dead! Give Us Our Money! The Cultural Origins of an African Work Ethic, Natal, South Africa, 1843–1900, by Keletso E. Atkins
Authors: Tallie T.J.
Published: October 2019

Keletso Atkins’s 1993 book The Moon Is Dead! Give Us Our Money! The Cultural Origins of an African Work Ethic, Natal, South Africa, 1843–1900, remains as prescient now as it was a quarter-century ago. Atkins’s insistence on a methodology that foregrounded African labor regimes as logically consistent, rational, and deserving of full consideration within a proto-capitalist colonial market has had a significant impact in Southern African historical scholarship, and these calls have been taken up with earnest by subsequent scholars. Perhaps most important, however, has been her self-aware approach as a black scholar writing to and for members of the diaspora, an academic achievement rarely repeated in her subfield.
Differences in PD-L1–Expressing Macrophages and Immune Microenvironment in Testicular Germ Cell Tumors
Authors: Sadigh Sam , Farahani Sahar J , Shah Abhishek , Vaughn David , Lal Priti
Published: October 2019

Objectives

To characterize the tumor microenvironment of testicular germ cell tumors (GCTs) using immunohistochemical markers.

Methods

Seventy-seven orchiectomies, including 36 nonmetastatic (NM) seminomas, 15 metastatic (M) seminomas, 13 nonmetastatic nonseminomatous germ cell tumors (NSGCTs), and 13 metastatic NSGCTs, were studied with PD-1, PD-L1, FOXP3, CD68, CD163, and mismatch repair (MMR) immunohistochemistry. FOXP3+ and PD-1+ tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) expressing CD68 and CD163 were enumerated. PDL-1 expression was evaluated on tumor cells and macrophages.

Results

GCTs primarily express PD-L1 on TAMs, except choriocarcinoma, where true tumor cell positivity was noted. Seminomas reveal increased intratumoral PD-L1+ TAMs compared with NSGCTs (P < .05). Activated TILs are increased in NM-seminomas compared with M-seminomas (P < .05). All GCTs retained MMR expression.

Conclusions

Robust PD-L1+ TAMs are significantly expanded in seminomas compared with NSGCTs. Among all GCTs, only choriocarcinoma cells reveal true positivity for PD-L1. These findings expand the realm of potentially targeted treatments for GCTs.
YouTube for Cosmetic Plastic Surgery: An Effective Patient Resource?
Authors: Ward Brittany , Ayyala Haripriya S , Zhang Kathy , Manuskhani Priya A , Paskhover Boris , Lee Edward S
Published: October 2019

Background

YouTube is increasingly being utilized as a major educational resource by patients. It is important for plastic surgeons to understand the quality and characteristics of videos that patients are likely to view about procedures of interest.

Objectives

The aim of this study was to evaluate the quality of the videos that patients are most likely to encounter when searching YouTube for the most common cosmetic plastic surgery procedures.

Methods

Based on Google Trends data, the most searched medical and colloquial terms were identified for common cosmetic surgery procedures: “abdominoplasty,” “tummy tuck,” “breast augmentation,” “boob job,” “liposuction,” “lipo,” “mastopexy,” “breast lift,” “reduction mammoplasty,” and “breast reduction.” On YouTube, videos were searched by relevance (default) and view count; the top 10 results were collected in each group and rated according to the DISCERN criteria. Each video was assigned an overall and bias DISCERN score (DS). A score of 1 indicates high bias and low overall quality and a score of 5 indicates the opposite.

Results

In total, 143 unique videos were identified, which resulted in a mean bias DS of 2.29 and mean overall DS of 2.44. Seventy-two videos included US board-certified plastic surgeons and 58 were classified as patient experience. Videos had 667,373,209 total views and were an average of 4.27 years old. Videos including US board-certified plastic surgeons were of significantly higher quality and showed lower bias than videos without these practitioners (P < 0.05).

Conclusions

Overall, YouTube videos showed high bias and low quality. Plastic surgeons should be aware of this popular resource and counsel patients about the bias that is often present. Plastic surgeons and academic plastic surgery organizations should strive to upload high-quality, unbiased videos to provide patients with a more appropriate resource.
Emotional Interference in Early Adolescence: Positive Reinforcement Modulates the Behavioral and Neural Effects of Negative Emotional Distracters
Authors: Jones Neil P , Schlund Michael , Kerestes Rebecca , Ladouceur Cecile D
Published: October 2019

Limited research has examined functioning within fronto-limbic systems subserving the resistance to emotional interference in adolescence despite evidence indicating that alterations in these systems are implicated in the developmental trajectories of affective disorders. This study examined the functioning of fronto-limbic systems subserving emotional interference in early adolescence and whether positive reinforcement could modulate these systems to promote resistance to emotional distraction. Fifty healthy early adolescents (10–13 years old) completed an emotional delayed working memory (WM) paradigm in which no distractors (fixation crosshair) and emotional distracters (neutral and negative images) were presented with and without positive reinforcement for correct responses. WM accuracy decreased with negative distracters relative to neutral distracters and no distracters, and activation increased in amygdala and prefrontal cortical (PFC) regions (ventrolateral, dorsomedial, ventromedial, and subgenual anterior cingulate) with negative distracters compared with those with no distracters. Reinforcement improved performance and reduced activation in the amygdala, dorsomedial PFC, and ventrolateral PFC. Decreases in amygdala activation to negative distracters due to reinforcement mediated observed decreases in reaction times. These findings demonstrate that healthy adolescents recruit similar fronto-limbic systems subserving emotional interference as adults and that positive reinforcement can modulate fronto-limbic systems to promote resistance to emotional distraction.
Behavioral Pharmacology of Novel Kappa Opioid Receptor Antagonists in Rats
Authors: Page Sarah , Mavrikaki Maria M , Lintz Tania , Puttick Daniel , Roberts Edward , Rosen Hugh , Carroll F Ivy , Carlezon William A , Chartoff Elena H
Published: October 2019

Background

New treatments for stress-related disorders including depression, anxiety, and substance use disorder are greatly needed. Kappa opioid receptors are expressed in the central nervous system, including areas implicated in analgesia and affective state. Although kappa opioid receptor agonists share the antinociceptive effects of mu opioid receptor agonists, they also tend to produce negative affective states. In contrast, selective kappa opioid receptor antagonists have antidepressant- and anxiolytic-like effects, stimulating interest in their therapeutic potential. The prototypical kappa opioid receptor antagonists (e.g., norBNI, JDTic) have an exceptionally long duration of action that complicates their use in humans, particularly in tests to establish safety. This study was designed to test dose- and time-course effects of novel kappa opioid receptor antagonists with the goal of identifying short-acting lead compounds for future medication development.

Methods

We screened 2 novel, highly selective kappa opioid receptor antagonists (CYM-52220 and CYM-52288) with oral efficacy in the warm water tail flick assay in rats to determine initial dose and time course effects. For comparison, we tested existing kappa opioid receptor antagonists JDTic and LY-2456302 (also known as CERC-501 or JNJ-67953964).

Results

In the tail flick assay, the rank order of duration of action for the antagonists was LY-2456302 < CYM-52288 < CYM-52220 << JDTic. Furthermore, LY-2456302 blocked the depressive (anhedonia-producing) effects of the kappa opioid receptor agonist U50,488 in the intracranial self-stimulation paradigm, albeit at a higher dose than that needed for analgesic blockade in the tail flick assay.

Conclusions

These results suggest that structurally diverse kappa opioid receptor antagonists can have short-acting effects and that LY-2456302 reduces anhedonia as measured in the intracranial self-stimulation test.
Quantum study of inelastic processes in low-energy calcium–hydrogen collisions
Authors: Belyaev A K , Vlasov D V , Mitrushchenkov A , Feautrier N
Published: October 2019

Cross-sections and rate coefficients for the partial inelastic processes in calcium–hydrogen collisions are calculated by means of the quantum reprojection method for nuclear dynamics based on the accurate ab initio electronic structure data. That is, the atomic data for the 110 inelastic processes of excitation, de-excitation, ion-pair formation, and mutual neutralization in Ca  + H and Ca+  + H− collisions are computed for all transitions between the 11 low-lying CaH(2Σ+) molecular states including ionic one. The quantum chemical data are used in a hybrid diabatic representation, which is derived from the adiabatic representation. It is found that the largest rate coefficients correspond to the mutual neutralization processes. At the temperature 6000 K, the maximal rate is equal to $4.37 \times 10^{-8}\, \mathrm{cm}^{3}\,\mathrm{s}^{-1}$. It is shown that the large-valued rates are determined by long-range ionic–covalent interactions with final binding energies from the optimal window, while moderate- and low-valued rates by both long- and short-range non-adiabatic regions with final energies outside of the optimal window.
Pathogen-Negative Sepsis—An Opportunity for Antimicrobial Stewardship
Authors: Lockhart Gabriel C , Hanin Jacob , Micek Scott T , Kollef Marin H
Published: October 2019

Sepsis is a common reason for empiric antibiotics among hospitalized patients. We found that the median duration of empiric antibiotics (interquartile range) was 6 (4–9) days among 1047 survivivors with pathogen-negative sepsis. These findings suggest that patients with pathogen-negative sepsis could represent an important opportunity for antimicrobial stewardship.
Health Information Exchange: A Novel Re-linkage Intervention in an Urban Health System
Authors: Sharp Joseph , Angert Christine D , Mcconnell Tyania , Wortley Pascale , Pennisi Eugene , Roland Lisa , Mehta C Christina , Armstrong Wendy S , Shah Bijal , Colasanti Jonathan A
Published: October 2019

Background

Public health information exchanges (HIEs) link real-time surveillance and clinical data and can help to re-engage out-of-care people with HIV (PWH).

Methods

We conducted a retrospective cohort study of out-of-care PWH who generated an HIE alert in the Grady Health System (GHS) Emergency Department (ED) between January 2017 and February 2018. Alerts were generated for PWH who registered in the GHS ED without Georgia Department of Public Health (GDPH) CD4 or HIV-1 RNA in the prior 14 months. The alert triggered a social work (SW)–led re-linkage effort. Multivariate logistic regression analyses used HIE-informed SW re-linkage efforts as the independent variable, and linkage to care and 3- and 6-month viral suppression (HIV-1 RNA < 200 c/mL) as primary outcomes. Patients admitted to the hospital were excluded from primary analysis.

Results

One hundred forty-seven out-of-care patients generated an alert. Ninety-eight were included in the primary analysis (mean age [SD], 41 ± 12 years; 70% male; 93% African American), and 20 received the HIE-informed SW intervention. Sixty percent of patients receiving the intervention linked to care in 6 months, compared with 35% who did not. Patients receiving the intervention were more likely to link to care (adjusted risk ratio [aRR], 1.63; 95% confidence interval [CI], 0.99–2.68) and no more likely to achieve viral suppression (aRR, 1.49; 95% CI, 0.50–4.46) than those who did not receive the intervention.

Conclusions

An HIE-informed, SW-led intervention systematically identified out-of-care PWH and may increase linkage to care for this important population. HIEs create an opportunity to intervene with linkage and retention strategies.
Patient-reported outcomes in RA care improve patient communication, decision-making, satisfaction and confidence: qualitative results
Authors: Bartlett Susan J , De Leon Elaine , Orbai Ana-Maria , Haque Uzma J , Manno Rebecca L , Ruffing Victoria , Butanis Alessandra , Duncan Trisha , Jones Michelle R , Leong Amye , Perin Jamie , Smith Katherine Clegg , Bingham Clifton O
Published: October 2019

Objective

To evaluate the impact of integrating patient-reported outcomes (PROs) into routine clinics, from the perspective of patients with RA, clinicians and other staff.

Methods

We conducted a prospective cohort study using a mixed methods sequential explanatory design at an academic arthritis clinic. RA patients completed selected Patient-Reported Outcomes Measurement Information System measures on tablets in the waiting room. Results were immediately available to discuss during the visit. Post-visit surveys with patients and physicians evaluated topics discussed and their impact on decision making; patients rated confidence in treatment. Focus groups or interviews with patients, treating rheumatologists and clinic staff were conducted to understand perspectives and experiences.

Results

Some 196 patients and 20 rheumatologists completed post-visit surveys at 816 and 806 visits, respectively. Focus groups were conducted with 24 patients, 10 rheumatologists and 4 research/clinic staff. PROs influenced medical decision-making and RA treatment changes (38 and 18% of visits, respectively). Patients reported very high satisfaction and treatment confidence. Impact on clinical workflow was minimal after a period of initial adjustment. PROs were valued by patients and physicians, and provided new insight into how patients felt and functioned over time. Reviewing results together improved communication, and facilitated patient-centred care, shared decision making, and the identification of new symptoms and contributing psychosocial/behavioural factors.

Conclusion

PRO use at RA visits was feasible, increased understanding of how disease affects how patients feel and function, facilitated shared decision-making, and was associated with high patient satisfaction and treatment confidence.
OPTIMIZATION OF THE RADIOACTIVE AEROSOL SAMPLING AND MEASURING PROCEDURE WITH RESPECT TO RADON CONCENTRATION IN THE AIR
Authors: Hýža Miroslav , Rulík Petr , Bednář Vojtěch
Published: October 2019

High-volume aerosol samplers combined with laboratory analysis using high-resolution gamma ray spectrometry allow determining artificial radionuclides in the atmosphere at sub μBq/m3 levels. A major drawback of this procedure is a significant delay of the analysis result after any potential radioactive contamination deposition on the aerosol filter. Within the scope of the HAMRAD project, an autonomous device was developed in order to increase the sampling and measuring frequency. This approach yields higher detection limits (minimum detectable activity concentration [MDAC]) due to the deposited activity of radon decay products on the filter. In order to quantify the radon effect, a simple mathematical model was developed to predict MDAC for the particular radionuclide of interest for the given background conditions. It was found that MDAC can vary by a factor of ~2 for typical ‘radon’ conditions (~10 Bq/m3) at SÚRO Prague and by a factor up to 5 for high radon concentration (100 Bq/m3).
ASSOCIATION OF 210Po CONTENT IN URINE WITH CONCENTRATION OF 222Rn IN DWELLINGS
Authors: Valdezová Petra , Hölgye Zoltán , Fojtíková Ivana , Kotík Lukáš
Published: October 2019

Effect of indoor radon concentrations higher than 500 Bq m−3 in dwellings on excretion of 210Po was studied in 28 volunteers. The study was further augmented by following eight individuals from the group for 5 months at 1-month intervals. Association between 222Rn concentration in homes and 210Po excretion was found when the dataset containing values of the studied 27 subjects was combined with data on 40 Prague inhabitants from the previous study. Sources of uncertainties involved in the analysis are discussed.
Parental Proxy PROMIS Pain Interference Scores are Only Modestly Concordant With Their Child’s Scores
Authors: Scott Eric L. , Foxen-Craft Emily , Caird Michelle , Philliben Riley , deSebour Trevor , Currier Emily , Voepel-Lewis Terri
Published: October 2019

Objectives:

Pediatric patients with chronic musculoskeletal conditions such as idiopathic scoliosis awaiting surgical correction can experience pain that interferes with their daily functioning. Reports of this interference are commonly gathered from patients through the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference Scale and through parent-proxy scores. However, the child and parent/caregiver reports vary. To provide appropriate treatment for young patients with pain, the nature of the discrepancies and under which circumstances the reports differ needs to be understood. This report offers new information on the level of concordance among parent and child report of pain interference within this patient population, and which parent and child characteristics may influence concordance rates.

Methods:

Youth (age=10 to 17 y) with a history of musculoskeletal disorders, including idiopathic scoliosis, under consideration for surgical correction of that scoliosis and parent/caregiver dyads (n=103) completed the PROMIS Pain Interference Scale during an orthopedic presurgical visit. The current data was taken from a larger study examining postsurgical pain among patients undergoing orthopedic surgical procedures to correct scoliosis. The purpose of the current study was to measure the degree of agreement between parent and child reports of pain interference and discovery of relationships among predictors of pain interference score correspondence among dyads.

Results:

Correspondence between parent/caregiver and child reports of pain interference was modest (intraclass correlation coefficient=0.530). In total, 46% of dyads had similar pain interference scores, whereas 24% of parents reported higher pain interference in comparison to their child, the remaining 30% reported lower pain interference in relation to their child’s report. Among children where discrepancies appeared, using logistic regression models, only child catastrophizing scores were associated with differences in parent and child estimation of child’s pain interference scores. No parental characteristics predicted discrepancies between dyad pain interference reports.

Discussion:

Parent-proxy and child reports generally correspond, but when discrepant, 24% of parents reported higher pain interference in relationship to the child report of pain interference and 31% noted less intense pain interference than their child’s pain interference. Given these results, care should be taken when interpreting parent reports of child pain interference, especially when a child reports higher degrees of pain interference.
Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder
Authors: Kingsberg Sheryl A. , Clayton Anita H. , Portman David , Williams Laura A. , Krop Julie , Jordan Robert , Lucas Johna , Simon James A.
Published: October 2019

OBJECTIVE:

To evaluate the safety and efficacy of bremelanotide for the treatment of premenopausal women with hypoactive sexual desire disorder.

METHODS:

Two identical phase 3, randomized, double-blind, placebo-controlled, multicenter clinical trials (RECONNECT) evaluated the safety and efficacy of bremelanotide 1.75 mg administered subcutaneously as needed in premenopausal women with hypoactive sexual desire disorder. Patients were randomized 1:1 to 24 weeks of treatment with bremelanotide or placebo. Sample size was estimated based on simulations from key endpoints in patients with hypoactive sexual desire disorder from a prior trial. Coprimary efficacy endpoints were change from baseline to end-of-study in the Female Sexual Function Index–desire domain score and Female Sexual Distress Scale–Desire/Arousal/Orgasm item 13.

RESULTS:

Study 301 began on January 7, 2015, and concluded on July 26, 2016. Study 302 began on January 28, 2015, and concluded on August 4, 2016. Of the 1,267 women randomized, 1,247 and 1,202 were in the safety and efficacy (modified intent-to-treat) populations, respectively. Most participants were white (85.6%), from U.S. sites (96.6%), and had a mean age of 39 years. From baseline to end-of-study, women taking bremelanotide had statistically significant increases in sexual desire (study 301: 0.30, P<.001; study 302: 0.42, P<.001; integrated studies 0.35, P<.001) and statistically significant reductions in distress related to low sexual desire (study 301: −0.37, P<.001; study 302: −0.29, P=.005; integrated studies −0.33, P<.001) compared with placebo. Patients taking bremelanotide experienced more nausea, flushing, and headache (10% or more in both studies) compared with placebo.

CONCLUSIONS:

Both studies demonstrated that bremelanotide significantly improved sexual desire and related distress in premenopausal women with hypoactive sexual desire disorder. The safety profile was favorable. Most treatment-emergent adverse events were related to tolerability and the majority were mild or moderate in intensity.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02333071 (study 301) and NCT02338960 (study 302).

FUNDING SOURCE:

Palatin Technologies, Inc., and AMAG Pharmaceuticals, Inc.
Methadone, Buprenorphine, or Detoxification for Management of Perinatal Opioid Use Disorder
Authors: Premkumar Ashish , Grobman William A. , Terplan Mishka , Miller Emily S.
Published: October 2019

OBJECTIVE:

To estimate whether methadone, buprenorphine, or detoxification treatment is the most cost-effective approach to the management of opioid use disorder (OUD) during pregnancy.

METHODS:

We created a decision analytic model that compared the cost effectiveness (eg, the marginal cost of the strategy in U.S. dollars divided by the marginal effectiveness of the strategy, measured in quality-adjusted life-years [QALYs]) of initiation of methadone, buprenorphine, or detoxification in treatment of OUD during pregnancy. Probabilities, costs, and utilities were estimated from the existing literature. Incremental cost-effective ratios for each strategy were calculated, and a ratio of $100,000 per QALY was used to define cost effectiveness. One-way sensitivity analyses and a Monte Carlo probabilistic sensitivity analysis were performed.

RESULTS:

Under base assumptions, initiation of buprenorphine was more effective at a lower cost than either methadone or detoxification and thus was the dominant strategy. Buprenorphine was no longer cost effective if the cost of methadone was 8% less than the base-case estimate ($1,646/month) or if the overall costs of detoxification were 121% less than the base-case estimate for the detoxification cost multiplier, which was used to increase the values of both inpatient and outpatient management of detoxification by a factor of 2. Monte Carlo analyses revealed that buprenorphine was the cost-effective strategy in 70.5% of the simulations. Direct comparison of buprenorphine with methadone demonstrated that buprenorphine was below the incremental cost-effective ratio in 95.1% of simulations; direct comparison between buprenorphine and detoxification demonstrated that buprenorphine was below the incremental cost-effective ratio in 45% of simulations.

CONCLUSION:

Under most circumstances, we estimate that buprenorphine is the cost-effective strategy when compared with either methadone or detoxification as treatment for OUD during pregnancy. Nonetheless, the fact that buprenorphine was not the cost-effective strategy in almost one out of three of simulations suggests that the robustness of our model may be limited and that further evaluation of the cost-effective approach to the management of OUD during pregnancy is needed.
Extracorporeal Therapies for Amniotic Fluid Embolism
Authors: Viau-Lapointe Julien , Filewod Niall
Published: October 2019

BACKGROUND:

Amniotic fluid embolism (AFE) is a catastrophic disease with significant mortality. Because the cardiopulmonary dysfunction associated with AFE is self-limited, the disease could be well suited to the use of extracorporeal therapies.

CASE:

A woman progressed into cardiac arrest immediately after an elective cesarean delivery. Owing to severe hypoxemia and hypotension, AFE was suspected and peripheral venoarterial extracorporeal membrane oxygenation was quickly initiated. Subsequent evolution was complicated by intrabdominal bleeding, which required massive transfusion and multiple surgeries. The patient recovered well, with a healthy newborn. We have identified 19 similar cases in the literature and present their outcomes as a series.

CONCLUSION:

Extracorporeal therapies can support severely ill women affected by AFE and could be considered even in the presence of disseminated intravascular coagulation and bleeding.
Peripartum Outcomes Before and After Hurricane Harvey
Authors: Mendez-Figueroa Hector , Chauhan Suneet P. , Tolcher Mary C. , Shamshirsaz Alireza A. , Sangi-Haghpeykar Haleh , Pace Ryan M. , Chu Derrick M. , Aagaard Kjersti
Published: October 2019

OBJECTIVE:

To evaluate the association between Hurricane Harvey landfall with maternal and neonatal morbidity.

METHODS:

Using an institutional perinatal database from two hospitals in Houston, Texas, women with nonanomalous singletons delivering after 24 weeks of gestation between August 2011 and June 2018 were included. To evaluate the possible association of hurricane landfall with pregnancy outcomes, gravid women delivering within 280 days (40 weeks of gestation) on or after August 25, 2017 (the day of hurricane landfall) were categorized as exposed, and women who delivered before August 25, 2017, were the reference group. Composite maternal morbidity included any of the following: hypertensive disorders of pregnancy, chorioamnionitis, endometritis, blood transfusion, peripartum hysterectomy, maternal critical care admission, pulmonary edema, or maternal death. Composite neonatal morbidity included any of the following: 5-minute Apgar score 3 or less, respiratory distress syndrome, use of ventilator or continuous positive airway pressure, suspected newborn sepsis, seizure, stillbirth, or neonatal death. Adjusted odds ratios (aORs) were calculated after correcting for possible confounders identified on univariate analysis. Disruption in outcome trends were measured in time series analyses.

RESULTS:

Of 40,502 deliveries in our database, 29,179 (72%) met the inclusion criteria, with 3,842 (13.2%) delivering within 280 days of Hurricane Harvey landfall. Women delivering after Hurricane Harvey were on average less likely to be obese and more likely to be older, Caucasian, married, have a household income higher than $75,000, a high school education, and private insurance. However, compared with the cohort of gravid patients who delivered before Hurricane Harvey, composite maternal morbidity increased by 27% (11.5% vs 14.7%, aOR 1.27, 95% CI 1.14–1.42) after the storm. Composite neonatal morbidity increased by 50% (7.8% vs 11.9%, aOR 1.52, 95% CI 1.34–1.71). In time series analyses, we observed a significant shift in composite maternal morbidity specific to women of low socioeconomic status (estimate 2.87, P=.028).

CONCLUSION:

Despite having fewer at-risk baseline characteristics, gravid patients delivering after landfall by Hurricane Harvey had a significantly higher likelihood of adverse outcomes as did their neonates.
A Comparison of Two Methods of Catheter Management After Pelvic Reconstructive Surgery
Authors: Boyd Sarah S. , O'Sullivan David M. , Tunitsky-Bitton Elena
Published: October 2019

OBJECTIVE:

To compare effects on activity between two catheter management systems after failed voiding trial after pelvic reconstructive surgery.

METHODS:

Women with a failed postoperative voiding trial after reconstructive pelvic surgeries were randomized to plug–unplug or continuous drainage catheters. The primary outcome was a mean activity assessment scale score. Secondary outcomes included urinary tract infection (UTI), time to passing outpatient voiding trial, and patient satisfaction. Enrollees who passed the voiding trial were assigned to a “Reference” arm. Ninety participants (30 per arm) provided more than 80% power to detect an effect size of 0.33 in the primary outcome, using a two-sided alpha of 0.05.

RESULTS:

Sixty-three patients were randomized (32 plug–unplug, 31 continuous drainage). The first 30 participants discharged without a catheter comprised the reference arm. There was no difference in postoperative activity assessment scale scores (total: plug–unplug 70.3, continuous drainage 67.7, reference arm 79.4; P=.090) between arms. Women in the continuous drainage arm noted more difficulty compared with the plug–unplug arm when managing the catheter “during the day” (P=.043) and “all the time” (P=.049) and felt the catheter impeded activities (P=.012) and wearing clothes (P=.005). The catheter arms had significantly higher rates of culture-positive UTI compared with the reference arm (58.7% vs 6.7%, P<.001). However, rate of UTI did not differ between catheter arms (plug–unplug, 68.8% vs continuous drainage, 48.4%, P=.625). The majority of patients passed their outpatient voiding trials at the initial postoperative visit (plug–unplug 71.9%, continuous drainage 58.1%, P=.250). There was no difference in patient satisfaction, with the majority reporting they were “very satisfied” (plug–unplug 78.1%, continuous drainage 80.0%, reference 66.7%, P=.202).

CONCLUSION:

Postoperative activity does not differ in patients discharged with plug–unplug or continuous drainage catheters, but those with plug–unplug perceive easier management and ability to complete activities of daily living. The plug–unplug method is an acceptable alternative to traditional catheterization after pelvic reconstructive surgery.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT03071211.
Long-term Risk of Reoperation After Synthetic Mesh Midurethral Sling Surgery for Stress Urinary Incontinence
Authors: Berger Alexander A. , Tan-Kim Jasmine , Menefee Shawn A.
Published: October 2019

OBJECTIVE:

To measure the long-term reoperation risk after synthetic mesh midurethral sling surgery.

METHODS:

This retrospective cohort study evaluated all patients who underwent a midurethral sling surgery for stress urinary incontinence (SUI) (2005–2016) within a large managed care organization of 4.5 million members. We queried the system-wide medical record for Current Procedural Terminology and International Classification of Diseases, 9th or 10th Revision codes for patient data, and implant registry coding to assess the sling type. The primary outcome was the overall reoperation rate after midurethral sling, with secondary outcomes being reoperation for mesh revision, or removal and recurrent SUI. We used cumulative incidence to calculate reoperation risk as a function of time at least 1 year, least 5 years, and at least 9 years. We compared demographics, characteristics, and reoperation of patients using χ2 and Wilcoxon rank sum, and we used a Cox proportional hazards model to calculate adjusted hazard ratios.

RESULTS:

In this cohort of 17,030 patients treated with primary midurethral slings, the overall reoperation rate was 2.1% (95% CI 1.9–2.4%) at 1 year, 4.5% (95% CI 4.1–4.8%) at 5 years, and 6.0% (95% CI 5.5–6.5%) at 9 years. Risk of reoperation was affected by race (P=.04), with Asian or Pacific Islander patients having a lower reoperation rate when compared with white patients. Reoperation rate for mesh revision or removal was 0.7% (95% CI 0.6–0.8%) at 1 year, 1.0% (95% CI 0.8–1.1%) at 5 years, and 1.1% (95% CI 0.9–1.3%) at 9 years. Reoperation for recurrent SUI was 1.6% (95% CI 1.4–1.8%) at 1 year, 3.9% (95% CI 3.5–4.2%) at 5 years, and 5.2% (95% CI 4.7–5.7%) at 9 years. Risk of reoperation for recurrent SUI was affected by the type of sling, with reoperation more common after single-incision compared with retropubic sling (adjusted hazard ratio 1.5 [95% CI 1.06–2.11] P=.03).

CONCLUSION:

Midurethral slings have a low long-term risk of reoperation for mesh revision or removal, and recurrent SUI, adding to the evidence of their safety and efficacy for the treatment of women with SUI.
A monogenic autoinflammatory disease with fatal vasculitis: deficiency of adenosine deaminase 2
Authors: Sahin Sezgin , Adrovic Amra , Kasapcopur Ozgur
Published: October 2019

Purpose of review

To recap the expanding clinical spectrum, genotype–phenotype associations and treatment options in the light of recently published articles regarding the deficiency of adenosine deaminase 2 (DADA2).

Recent findings

Whole-exome sequencing enabled novel clinical phenotypes associated withADA2mutations. Since its discovery, the phenotypic spectrum of DADA2 has substantially expanded to cover Diamond–Blackfan anaemia, cytopenia and immunodeficiency syndromes. In addition to elevated TNF alpha levels, increased levels of interferon-stimulated genes were also detected in patients with DADA2. Given the absence of clinical trials until now, no standard treatment strategy exists for DADA2. Currently, anti-TNF alpha agents are the mainstay of treatment, based on the data both from the initial two reports and from subsequent studies. However, it is still unclear how to manage asymptomatic patients withADA2mutation and/or with absent ADA2 activity and what is the optimal duration of anti-TNF therapy.

Among a total of 206 DADA2 patients described so far, the overall mortality was found as 8.3%. Biallelic homozygous G47R mutations were mostly associated with a vascular phenotype, whereas patients with homozygous R169Q mutations seem to display a mixed clinical phenotype including vascular, haematological and immunological manifestations. HSCT should be reserved as a curative treatment option for DADA2 patients unresponsive to the anti-TNF therapy, as it carries a significant morbidity.
Novel therapeutic options for radioiodine-refractory thyroid cancer: redifferentiation and beyond
Authors: Bulotta Stefania , Celano Marilena , Costante Giuseppe , Russo Diego
Published: October 2019

Purpose of review

Radioiodine-refractory thyroid cancers represent the main cause of thyroid cancer-related death. At present, targeted therapies with multikinase inhibitors represent a unique therapeutic tool, though they have limited benefit on patient survival and severe drug-associated adverse events. This review summarizes current treatment strategies for radioiodine-refractory thyroid cancer and focuses on novel approaches to redifferentiate thyroid cancer cells to restore responsiveness to radioiodine administration.

Recent findings

We summarize and discuss recent clinical trial findings and early data from real-life experiences with multikinase-inhibiting drugs. Possible alternative strategies to traditional redifferentiation are also discussed.

The current review focuses primarily on the major advancements in the knowledge of the pathophysiology of iodine transport and metabolism and the genetic and epigenetic alterations occurring in thyroid neoplasia as described using preclinical models. Results of clinical studies employing new compounds to induce thyroid cancer cell redifferentiation by acting against specific molecular targets are also discussed. Finally, we describe the current scenario emerging from such findings as well as future perspectives.
Is It the Surgery or the Block? Incidence, Risk Factors, and Outcome of Nerve Injury following Upper Extremity Surgery
Authors: Droog Wouter , Lin D-Yin , van Wijk Jan J. , Ho-Asjoe Raissah C. H. , Coert J. Henk , Stolker Robert Jan , Galvin Eilish M.
Published: October 2019

Background:

Although numerous studies have addressed the topic of postoperative nerve injury, debate continues to exist on its exact incidence, risk factors, etiology, and functional outcome. The aim of this study is to investigate the incidence of nerve injury and to identify patient, anesthetic, and surgical factors pertaining to perioperative nerve injury. Also, long-term nerve injury outcomes were assessed in terms of functionality.

Methods:

A total of 297 patients, scheduled for elective distal upper extremity surgery, were prospectively included. At various time points, patients were screened for new onset nerve injury by means of clinical examination and questionnaires (including the Quick Disabilities of the Arm, Shoulder and Hand functionality measure).

Results:

New nerve injury was diagnosed in 14 patients [4.7% (95% CI, 2.8–7.8)], but no causative risk factors were identified. The exact origin of nerve injury is suspected to be surgical in 11 cases. At 4 years postoperatively, 5 of the 14 patients with nerve injury (36%) were still symptomatic and had reduced functionality relative to preoperative status.

Conclusions:

This study demonstrates an incidence of all cause nerve injury of 4.7%. No specific patient, anesthetic, or surgical risk factors are identified and, importantly, patients who received regional anesthesia are not at more risk of nerve injury than those who received general anesthesia. The exact origin of nerve injury is very difficult to determine, but is suspected to be caused by direct surgical trauma in most cases. Four years following the nerve injury, approximately 40% of the patients with new onset nerve injury have reduced functionality.