bluuebunny/crossref_metadata_2025 huggingface dataset:
History of the Military Nurse Corps and the 1918 Influenza Pandemic: Lessons for the 2019 Coronavirus Pandemic
Authors: Talbot Laura A , Metter E Jeffrey , King Heather
Published: December 2020

During World War I, the 1918 influenza pandemic struck the fatigued combat troops serving on the Western Front. Medical treatment options were limited; thus, skilled military nursing care was the primary therapy and the best indicator of patient outcomes. This article examines the military nursing’s role in the care of the soldiers during the 1918 flu pandemic and compares this to the 2019 coronavirus pandemic.
Path Semantics for Indicative Conditionals
Authors: Santorio Paolo
Published: December 2020

The literature on indicative conditionals contains two appealing views. The first is the selectional view: on this view, conditionals operate by selecting a single possibility, which is used to evaluate the consequent. The second is the informational view: on this view, conditionals don’t express propositions, but rather impose constraints on information states of speakers. Both views are supported by strong arguments, but they are incompatible on their standard formulations. Hence it appears that we have to choose between mutually exclusive options. But the options are not exclusive. This paper develops a theory of the semantics and assertability of conditionals that is both selectional and informational. The theory vindicates the signature inferences of both selectional and informational theories, including so-called Conditionals Excluded Middle and principles about the interplay between conditionals and ‘might’. It also predicts some interesting and puzzling facts about the assertion of conditionals.
The non-monotonic, strong metallicity dependence of the wide-binary fraction
Authors: Hwang Hsiang-Chih , Ting Yuan-Sen , Schlaufman Kevin C , Zakamska Nadia L , Wyse Rosemary F G
Published: December 2020

The metallicity dependence of the wide-binary fraction (WBF) IN stellar populations plays a critical role in resolving the open question of wide-binary formation. In this paper, we investigate the metallicity ([Fe/H]) and age dependence of the WBF (binary separations between 103 and 104 au) for field F and G dwarfs within 500 pc by combining their metallicity and radial velocity measurements from LAMOST Data Release 5 (DR5) with the astrometric information from Gaia DR2. We show that the WBF strongly depends on the metallicity: as metallicity increases, the WBF first increases, peaks at [Fe/H] ≃ 0, and then decreases at the high-metallicity end. The WBF at [Fe/H] = 0 is about two times larger than that at [Fe/H] = −1 and +0.5. This metallicity dependence is dominated by the thin-disc stars. Using stellar kinematics as a proxy of stellar age, we show that younger stars have a higher WBF at fixed metallicity close to solar. We propose that multiple formation channels are responsible for the metallicity and age dependence. In particular, the positive metallicity correlation at [Fe/H] < 0 and the age dependence may be due to the denser formation environments and higher mass clusters at earlier times. The negative metallicity correlation at [Fe/H] > 0 can be inherited from the similar metallicity dependence of close binaries, and radial migration may play a role in enhancing the WBF around the solar metallicity.
H i intensity mapping with MeerKAT: 1/f noise analysis
Authors: Li Yichao , Santos Mario G , Grainge Keith , Harper Stuart , Wang Jingying
Published: December 2020

The nature of the time correlated noise component (the 1/f noise) of single dish radio telescopes is critical to the detectability of the H i signal in intensity mapping experiments. In this paper, we present the 1/f noise properties of the MeerKAT receiver system using South Celestial Pole tracking data. We estimate both the temporal power spectrum density and the 2D power spectrum density for each of the antennas and polarizations. We apply singular value decomposition to the data set and show that, by removing the strongest components, the 1/f noise can be drastically reduced, indicating that it is highly correlated in frequency. With two-mode subtraction, the knee frequency over a $20\,$ MHz averaging is about $3\times 10^{-3}\, {\rm Hz}$, indicating that the system induced 1/f-type variations are well under the thermal noise fluctuations over a few hundred seconds time-scales. We also show that such cleaning on the time ordered data has very little impact on the 21-cm signal itself. The 2D power spectrum shows that the 1/f-type variations are restricted to a small region in the time–frequency space, either with long-wavelength correlations in frequency or in time. This gives a wide range of cosmological scales where the H i signal can be measured without further need to calibrate the gain time fluctuations. Finally, we demonstrate that a simple power spectrum parameterization is sufficient to describe the data and provide fitting parameters for both the 1D and 2D power spectrum.
Spectral and polarization properties of black hole accretion disc emission: including absorption effects
Authors: Taverna R , Marra L , Bianchi S , Dovčiak M , Goosmann R , Marin F , Matt G , Zhang W
Published: December 2020

The study of radiation emitted from black hole accretion discs represents a crucial way to understand the main physical properties of these sources, and in particular the black hole spin. Beside spectral analysis, polarimetry is becoming more and more important, motivated by the development of new techniques which will soon allow to perform measurements also in the X- and γ-rays. Photons emitted from black hole accretion discs in the soft state are indeed expected to be polarized, with an energy dependence which can provide an estimate of the black hole spin. Calculations performed so far, however, considered scattering as the only process to determine the polarization state of the emitted radiation, implicitly assuming that the temperatures involved are such that material in the disc is entirely ionized. In this work we generalize the problem by calculating the ionization structure of a surface layer of the disc with the public code cloudy, and then by determining the polarization properties of the emerging radiation using the Monte Carlo code stokes. This allows us to account for absorption effects alongside scattering ones. We show that including absorption can deeply modify the polarization properties of the emerging radiation with respect to what is obtained in the pure-scattering limit. As a general rule, we find that the polarization degree is larger when absorption is more important, which occurs e.g. for low accretion rates and/or spins when the ionization of the matter in the innermost accretion disc regions is far from complete.
Dwarf galaxies and the black hole scaling relations
Authors: King Andrew , Nealon Rebecca
Published: December 2020

The sample of dwarf galaxies with measured central black hole masses M and velocity dispersions σ has recently doubled, and gives a close fit to the extrapolation of the M  - σ relation for more massive galaxies. We argue that this is difficult to reconcile with suggestions that the scaling relations between galaxies and their central black holes are simply a statistical consequence of assembly through repeated mergers. This predicts black hole masses significantly larger than those observed in dwarf galaxies unless the initial distribution of uncorrelated seed black hole and stellar masses is confined to much smaller masses than earlier assumed. It also predicts a noticeable flattening of the M  - σ relation for dwarfs, to M ∝ σ2 compared with the observed M ∝ σ4. In contrast black hole feedback predicts that black hole masses tend towards a universal M ∝ σ4 relation in all galaxies, and correctly gives the properties of powerful outflows recently observed in dwarf galaxies. These considerations emphasize once again that the fundamental physical black hole – galaxy scaling relation is between M and σ. The relation of M to the bulge mass Mb is acausal, and depends on the quite independent connection between Mb and σ set by stellar feedback.
The environment of FRB 121102 and possible relation to SGR/PSR J1745−2900
Authors: Katz J I
Published: December 2020

Variations of the dispersion measures (DM) and rotation measures (RM) of fast radio bursts (FRBs) 121102 indicate magnetic fields ∼3–17 mG in the dispersing plasma. The electron density may be ${\sim}10^4\,$ cm−3. The observed time scales ∼1 yr constrain the size of the plasma cloud. Increasing DM excludes simple models involving an expanding supernova remnant, and the non-zero RM excludes spherical symmetry. The varying DM and RM may be attributable to the motion of plasma into or out of the line of sight to or changing electron density within slower moving plasma. The extraordinarily large RM of FRB 121102 implies an environment, and possibly also a formation process and source, qualitatively different from those of other FRB. The comparable and comparably varying RM of SGR/PSR J1745−2900 suggests it as a FRB candidate. Appendix A discusses the age of FRB 121102 in the context of a ‘Copernican Principle’.
Neural network models for DMT-induced visual hallucinations
Authors: Schartner Michael M , Timmermann Christopher
Published: December 2020

The regulatory role of the serotonergic system on conscious perception can be investigated perturbatorily with psychedelic drugs such as N,N-Dimethyltryptamine. There is increasing evidence that the serotonergic system gates prior (endogenous) and sensory (exogenous) information in the construction of a conscious experience. Using two generative deep neural networks as examples, we discuss how such models have the potential to be, firstly, an important medium to illustrate phenomenological visual effects of psychedelics—besides paintings, verbal reports and psychometric testing—and, secondly, their utility to conceptualize biological mechanisms of gating the influence of exogenous and endogenous information on visual perception.
Medawar and the immunological paradox of pregnancy: in context
Authors: Male Victoria
Published: December 2020

In 1953, Peter Medawar defined ‘the immunological paradox of pregnancy’, whereby the semi-allogeneic foetus can survive for 9 months in its mother, while a semi-allogeneic graft would be rejected. Here, I revisit the immunological paradox of pregnancy, setting it in the context of the time in which it was proposed. I go on to examine the extent to which Medawar’s ideas on the subject have stood the test of time and how they have shaped reproductive immunology.
Individualized Aerobic Exercise in Neuromuscular Diseases: A Pilot Study on the Feasibility and Preliminary Effectiveness to Improve Physical Fitness
Authors: Voorn Eric L , Koopman Fieke S , Nollet Frans , Brehm Merel-Anne
Published: December 2020

Objective

Clear guidelines to prescribe aerobic exercise in neuromuscular diseases (NMD) are lacking, which hampers effective application in neuromuscular rehabilitation. This pilot study evaluated the feasibility and preliminary effectiveness of an individualized aerobic exercise program according to a recently developed training guide (B-FIT) to improve physical fitness in individuals with NMD.

Methods

Thirty-one individuals who were ambulatory and had 15 different slowly progressive NMD participated in a 4-month, polarized, home-based, aerobic exercise program. The program included 2 low-intensity sessions and 1 high-intensity session per week. Feasibility outcomes were the following: completion rate, proportion of followed sessions, adverse events, and participant and therapist satisfaction based on a self-designed questionnaire. Submaximal incremental exercise tests were used to assess the effects on physical fitness.

Results

Twenty-six participants (84%) completed the B-FIT program, and the proportion of followed sessions was >75%. Three adverse events were reported and resolved. Regarding satisfaction, participants (based on n = 9) reported feeling fitter, but training was considered insufficiently challenging. Physical therapists (n = 5) reported that B-FIT provides a clear, well-grounded guidance. They perceived the time investment for initiating the program and the carry-over to primary care as the main barriers. The mean (SD) submaximal heart rate (based on n = 20) reduced significantly by −6.5 beats per minute (95% CI = −11.8 to −1.2), from 121.7 (16.5) at baseline to 115.2 (14.3) after intervention. Submaximal ratings of perceived exertion, anaerobic threshold, and peak workload also improved significantly (P < .05).

Conclusion

The outcomes of this pilot study suggest that individualized aerobic exercise according to B-FIT is feasible and has potential to improve physical fitness in a wide variety of slowly progressive NMD. However, some barriers must be addressed before investigating the efficacy in a randomized controlled trial.

Impact

The outcomes of this study demonstrate the feasibility of individualized aerobic exercise according to the B-FIT training guide and the potential to improve physical fitness in NMD. Physical therapists indicated that the use of B-FIT provides a clear, well-grounded guidance. The training guide can support health care professionals in the application of aerobic exercise in adult neuromuscular rehabilitation.

Lay Summary

Individualized exercise according to the B-FIT training guide is feasible in a wide variety of slowly progressive NMD and might help improve physical fitness.
Reorganization or Liquidation: Bankruptcy Choice and Firm Dynamics
Authors: Corbae Dean , D’Erasmo Pablo
Published: December 2020

In this article, we ask how bankruptcy law affects the financial decisions of corporations and its implications for firm dynamics. According to current U.S. law, firms have two bankruptcy options: Chapter 7 liquidation and Chapter 11 reorganization. Using Compustat data, we first document capital structure and investment decisions of non-bankrupt, Chapter 11, and Chapter 7 firms. Using those data moments, we then estimate parameters of a general equilibrium firm dynamics model with endogenous entry and exit to include both bankruptcy options. Finally, we evaluate a bankruptcy policy change similar to one recommended by the American Bankruptcy Institute that amounts to a “fresh start” for bankrupt firms. We find that changes to the law can have sizable consequences for borrowing costs and capital structure which via selection affects productivity, as well as long run welfare.
Risk Factors for Surgical Site Infection after Minor Dermatologic Surgery
Authors: Delpachitra Meth , Heal Clare , Banks Jennifer , Charles Daniel , Sriharan Shampavi , Buttner Petra
Published: December 2020

BACKGROUND

Surgical site infection (SSI) after dermatologic surgery is associated with poor outcomes including increased recovery time, poor cosmesis, and repeat visits to doctors. Prophylactic antibiotics are prescribed to reduce these adverse outcomes. Identifying risk factors for SSI will facilitate judicious antibiotic prophylaxis.

OBJECTIVE

To identify risk factors for SSI after minor dermatologic surgery.

METHODS

Individual patient data from four large randomized controlled trials were combined to increase statistical power. A total of 3,819 adult patients requiring minor skin procedures at a single facility were recruited over a 10-year period. The main outcome measure was SSI.

MAIN RESULTS

A total of 298 infections occurred, resulting in an overall incidence of 7.8% (95% confidence interval [CI], 5.8–9.6), although the incidence varied across the four studies (P = .042). Significant risk factors identified were age (relative risk [RR], 1.01; 95% CI, 1.001–1.020; P = .008), excisions from the upper limbs (RR, 3.03; 95% CI, 1.76–5.22; P = .007) or lower limbs (RR, 3.99; 95% CI, 1.93–8.23; P = .009), and flap/two-layer procedures (RR, 3.23; 95% CI, 1.79–5.85; P = .008). Histology of the excised lesion was not a significant independent risk factor for infection.

CONCLUSIONS

This study demonstrated that patients who were older, underwent complex excisions, or had excisions on an extremity were at higher risk of developing an SSI. An awareness of such risk factors will guide evidence-based and targeted antibiotic prophylaxis.
Evaluating the Effectiveness of a Novel Skin Barrier Protectant in a Patient with Acute Radiodermatitis of the Vulva: A Case Report
Authors: Van Bever Leen , Claes Stefan , Robijns Jolien , Censabella Sandrine , Pannekoeke Luc , Van de Werf Evelyn , Bulens Paul
Published: December 2020

OBJECTIVE

To evaluate the use of a novel skin barrier protectant in a patient treated with radiotherapy for vulvar cancer.

METHODS

This case report was conducted in a radiotherapy department with two women undergoing radiotherapy for vulvar carcinoma. A novel skin barrier protectant was evaluated in one patient; the other underwent the institutional standard skin care protocol. Skin reactions and pain were evaluated using the Radiotherapy Oncology Group Criteria.

MAIN RESULTS

The patient who was treated with the skin protectant showed accelerated healing toward the end of radiotherapy, and this was accompanied with a decrease in pain (maximum pain score 6/10). In comparison, the patient treated with the standard skin care protocol had an extended healing process, experienced a higher pain level (maximum pain score 9/10), and required more nursing care.

CONCLUSIONS

This case report is the first to suggest that this novel skin barrier protectant could effectively manage acute radiodermatitis in patients with cancer. This case report hopes to lay the foundation for future randomized controlled trials with a larger and broader patient population.
Minimizing postoperative pulmonary complications in thoracic surgery patients
Authors: Kaufmann Kai , Heinrich Sebastian
Published: December 2020

Purpose of review

Quantification and optimization of perioperative risk factors focusing on anesthesia-related strategies to reduce postoperative pulmonary complications (PPCs) after lung and esophageal surgery.

Recent findings

There is an increasing amount of multimorbid patients undergoing thoracic surgery due to the demographic development and medical progress in perioperative medicine. Nevertheless, the rate of PPCs after thoracic surgery is still up to 30–50% with a significant influence on patients’ outcome. PPCs are ranked first among the leading causes of early mortality after thoracic surgery. Although patients’ risk factors are usually barely modifiable, current research focuses on procedural risk factors. From the surgical position, the minimal-invasive approach using video-assisted thoracoscopy and laparoscopy leads to a decreased rate of PPCs. The anesthesiological strategy to reduce the incidence of PPCs after thoracic surgery includes neuroaxial anesthesia, lung-protective ventilation, and goal-directed hemodynamic therapy.

The main anesthesiological strategies to reduce PPCs after thoracic surgery include the use of epidural anesthesia, lung-protective ventilation: PEEP (positive end-expiratory pressure) of 5–8 mbar, tidal volume of 5 ml/kg BW (body weight) and goal-directed hemodynamics: CI (cardiac index) ≥ 2.5 l/min per m2, MAD (Mean arterial pressure) ≥ 70 mmHg, SVV (stroke volume variation) < 10% with a total amount of perioperative crystalloid fluids ≤ 6 ml/kg BW (body weight) per hour.
Acetabular retroversion after triple pelvic osteotomy for Legg–Calvé–Perthes disease and its impact on the femoroacetabular impingement: a case/control study at 15 years of follow-up
Authors: Jeandel Clément , Cottalorda Jérôme , Chammas Pierre Emmanuel , Delpont Marion , Louahem’m’sabah Djamel
Published: December 2020

The objective of this study was to compare the effect of triple pelvic osteotomy (TPO) in Legg–Calvé–Perthes disease (LCPD) on acetabular version in a group of patients who developed a femoroacetabular impingement (FAI) and a control group without FAI. Patients who received a TPO for unilateral LCPD were retrospectively included. Patients with bilateral LCPDs, requiring TPO with femoral procedures, or with incomplete imaging were excluded. Seven patients with FAI (FAI+) and eight patients without FAI (FAI−) were evaluated at a mean follow-up of 14.8 years. The two groups were comparable in demographic data, age at diagnosis, Herring score, and BMI. We measured anatomical acetabular version on computed tomography scans, the difference (delta) of acetabular version between the operated hip and the healthy hip, the McKibbin (femoral version + acetabular version), Stulberg, and Tönnis scoring system. The two groups were not statistically different on the Stulberg and Tönnis scores. All operated hip acetabula were retroverted, FAI+: −8.41° (range, −44 to 10.5), FAI−: −3.38° (range, −37.3 to 11.5) (P = 0.61). The average delta was FAI+: 23.79° (range, 1.5–59.5), FAI−: 20.14° (range, 5–45.3) (P = 0.68). All seven patients of the FAI+ group have pathologic McKibbin index (<30°) versus only four of the FAI− group (P = 0.03). TPO induces acetabular retroversion in patients with LCPD. This retroversion, assessed in a static benchmark (anterior pelvic plane), does not in itself explain the FAI.
Alcohol Abuse and Alcohol Withdrawal Are Associated with Adverse Perioperative Outcomes Following Elective Spine Fusion Surgery
Authors: Han Lin , Han Hedong , Liu Hu , Wang Chenfeng , Wei Xin , He Jia , Lu Xuhua
Published: December 2020

Study Design.

Cross-sectional study.

Objective.

Alcohol abuse (AA) and alcohol withdrawal (AW), both belonging to alcohol use disorders, bring about vast health consequences, social issues, and financial burden in United States. This study aims to explore the relationship of AA and AW with perioperative outcomes following elective spine fusion surgery.

Summary of Background Data.

Large studies evaluating the outcomes of spine surgery in patients with AA or AW are lacking.

Methods.

We used the National Inpatient Sample (NIS) from 2006 to 2014 to extract records with a primary procedure of spinal fusion surgery. Multivariable regression analysis was used to assess the association of AA and AW with in-hospital mortality, perioperative complications, cost and length of stay (LOS).

Results.

Among 3,132,192 patients undergoing elective spinal fusion surgery, the prevalence of AA and AW was 1.14% (35,833) and 0.15% (4623), respectively. Among the AA admissions, 12.90% of patients developed AW. The incidence of overall complications was 6.14%, 10.15%, and 33.73% in patients without AA, with AA and with AW, respectively. After multivariable adjustment, AW was associated with elevated risk of overall complications (odds ratio [OR]: 4.51; 95% confidence interval [CI]: 3.86–5.27), neurologic (OR: 2.58; 95% CI: 1.62–4.12), respiratory (OR: 8.04; 95% CI: 6.62–9.77), cardiac (OR: 3.58; 95% CI: 2.60–4.93), gastrointestinal (OR: 2.31; 95%CI: 1.68–3.17), urinary and renal (OR: 2.68; 95% CI: 2.11–3.39), venous thromboembolism (OR: 3.06; 95% CI: 1.94–4.82), wound-related complications (OR: 3.84; 95% CI: 2.96–4.98) and in-hospital mortality (OR: 5.95; 95% CI: 3.25–10.90). AW was also linked to 40% higher cost and 85% longer LOS.

Conclusion.

Both AA and AW are associated with adverse outcomes in patients undergoing spinal fusion surgery with more pronounced risks for AW. Aggressive management in perioperative period is required to improve outcomes in these patients.

Level of Evidence: 3
Validation of the Yoruba Version of the Pain Self-Efficacy Questionnaire in Patients with Chronic Low Back Pain
Authors: Fatoye Francis , Mbada Chidozie Emmanuel , Oladayo Timothy Oluwaseun , Idowu Opeyemi Ayodiipo , Oyewole Olufemi O. , Fatoye Clara , Oke Kayode Israel
Published: December 2020

Study Design.

Cultural adaptation and psychometric analysis.

Objective.

This study determined the test–retest reliability, acceptability, internal consistency, divergent validity of the Yoruba pain self-efficacy questionnaire (PSEQ-Y). It also examined the ceiling and floor effects and the small detectable change (SDC) of the PSEQ-Y among patients with chronic low back pain (LBP).

Summary of Background Data.

There are various indigenous language translations of the PSEQ and none adapted to African language. However, translations of the PSEQ into Nigerian languages are not readily available.

Methods.

The validity testing phase of the study involved 131 patients with LBP, while 83 patients with LBP took part in the reliability phase. Following the Beaton recommendation for cultural adaptation of instruments, the PSEQ was adapted into the Yoruba language. The psychometric properties of the PSEQ-Y determined comprised: internal consistency, divergent validity, test–retest reliability, and SDC.

Results.

The mean age of the participants was 52.96 ± 17.3 years. The PSEQ-Y did not correlate with the Yoruba version of Visual Analogue Scale (VAS-Y) scores (r = –0.05; P = 0.59). The values for the internal consistency and the test–retest reliability of the PSEQ-Y were 0.79 and 0.86, with the 95% confidence interval of the test–retest reliability ranging between 0.82 and 0.90. The standard error of measurement (SEM) and the SDC of the PSEQ-Y were 1.2 and 3.3, respectively. The PSEQ-Y had no floor or ceiling effect, as none of the respondents scored either the minimal or maximal scores.

Conclusion.

This is the first study in Nigeria to culturally adapt PSEQ. The PSEQ-Y showed adequate psychometric properties similar to existing versions. Therefore, the tool can be used to assess pain self-efficacy in clinical and research settings and help to improve the health outcomes of patients chronic LBP.

Level of Evidence: 3
Less is More: Five-item Neck Disability Index to Assess Chronic Neck Pain Patients in Brazil
Authors: Barreto Felipe Souza , Avila Mariana Arias , Pinheiro Jocassia Silva , Almeida Mariana Quixabeira Guimarães , Ferreira Cheila de Sousa Bacelar , Fidelis-de-Paula-Gomes Cid André , Dibai-Filho Almir Vieira
Published: December 2020

Study Design.

Cross-sectional study.

Objective.

The aim of this study was to assess the structural validity of the Brazilian version of the Neck Disability Index (NDI) in patients with chronic neck pain.

Summary of Background Data.

NDI is widely used in clinical and scientific contexts, although its structure has not been evaluated in the Brazilian version.

Methods.

Native Brazilian Portuguese speakers, aged ≥18 years, with neck pain complaint of at least 3 months, and minimal pain rating of 3 points at rest or during neck movements were included. Exploratory factorial analysis (EFA) and confirmatory factorial analysis (CFA) were used. In EFA, the adequacy of the model was assessed using Bartlett test of sphericity and Kaiser-Meyer-Olkin test. In CFA, the goodness-of-fit was assessed by the indices: root mean square error of approximation with 90% of confidence interval, comparative fit index, Tucker-Lewis Index, standardized root mean square residual, and χ2/degree of freedom. Akaike information criterion (AIC) and Bayesian information criterion (BIC) were considered to compare the models.

Results.

Two hundred fifty-four participants with chronic neck pain were included. The NDI model with one domain and five items presented the most adequate goodness-of-fit indexes and the lowest values of AIC and BIC, when compared with models with one domain and 10, eight, or seven items, and with the model with two domains and 10 items.

Conclusion.

In the Brazilian context, the NDI version with one domain and five items (personal care, concentration, work, driving, and recreation) presents the best structure according to the factorial analysis.

Level of Evidence: 5
Mitogen-activated protein kinase blockade in melanoma: intermittent versus continuous therapy, from preclinical to clinical data
Authors: Tétu Pauline , Vercellino Laetitia , Reger de Moura Coralie , Baroudjian Barouyr , Dumaz Nicolas , Mourah Samia , Lebbé Céleste
Published: December 2020

Purpose of review

Although targeted therapy provides a high response rate and rapid disease control in advanced melanoma, most patients experience disease progression due to acquired resistance mechanisms leading to reactivation of mitogen-activated protein kinase pathway. The purpose of this article is to review the recently published data on the impact of an intermittent versus continuous dosing schedule of BRAF and MEK inhibition in advanced melanoma to determine the best approach in clinical practice.

Recent findings

Some preclinical studies have highlighted the concept that drug-resistant cells may also display drug dependency, such that intermittent dosing of targeted therapy may prevent the emergence of lethal drug resistance. Moreover, clinical observations have suggested that repeated treatment after a break or an intervening therapy may provide clinical benefit. However, recent preclinical and clinical studies have also failed to demonstrate an advantage of intermittent dosing and showed a similar efficacy of the intermittent versus continuous regimens of BRAF and MEK inhibitors in mice models and phase 2 clinical trial.

Owing to these discordant results, continuous dosing of BRAF and MEK inhibitors remains the optimal therapeutic approach until additional clinical data demonstrate the superiority of another combination or dosing regimen.
Baclofen and naltrexone, but not N-acetylcysteine, affect voluntary alcohol drinking in rats regardless of individual levels of alcohol intake
Authors: Minnaard A. Maryse , Ramakers Geert M.J. , Vanderschuren Louk J.M.J. , Lesscher Heidi M.B.
Published: December 2020

In humans, there is profound individual variation in the risk of alcohol use disorder (AUD). Because GABA, opioid and glutamate neurotransmission have been implicated in AUD, functional differences in these neural systems may underlie the individual vulnerability to AUD. We therefore determined the effects of drugs affecting GABA, opioid and glutamatergic neurotransmission on alcohol consumption in rats that differed in baseline alcohol intake. Subgroups of low-, medium- and high-alcohol-drinking rats were selected on the basis of alcohol consumption using an intermittent alcohol access procedure. The subgroups were treated with the GABAB receptor agonist baclofen, the opioid receptor antagonist naltrexone and the cysteine precursor N-acetylcysteine, and the effects on alcohol intake and preference were determined. Both baclofen and naltrexone reduced alcohol consumption, but N-acetylcysteine did not. These effects were comparable for low-, medium- and high-alcohol-drinking rats. However, there was a substantial degree of individual variation in the responsivity to baclofen and naltrexone, across the subgroups. Taken together, these results suggest that variation in alcohol consumption does not predict the responsivity to baclofen and naltrexone. This implies that individual variability in alcohol consumption on the one hand and sensitivity to treatment with these drugs on the other hand represent separate processes that likely involve distinct biological mechanisms.
Association between arterial stiffness and the clustering of metabolic syndrome risk factors: a systematic review and meta-analysis
Authors: Sequí-Domínguez Irene , Cavero-Redondo Iván , Álvarez-Bueno Celia , Saz-Lara Alicia , Mesas Arthur E. , Martínez-Vizcaíno Vicente
Published: December 2020

Objectives:

Metabolic syndrome (MetS) is a cluster of different cardiometabolic risk factors (CMRFs), and its different combinations with other CMRFs, such as arterial stiffness have been hypothesized to explain, at least partially, increased risk of cardiovascular disease. Thus, in this systematic review and meta-analysis, we aimed to synthesize the evidence regarding the association between the clustering of MetS-related CMRFs and arterial stiffness measured using pulse wave velocity (PWV).

Methods:

Original studies analysing the association between arterial stiffness, measured using PWV, and MetS were systematically searched. Pooled effect size estimates and their respective 95% confidence intervals (CI) were calculated using the DerSimonian and Laird method for two separate analyses: the diagnosis of MetS and PWV values and the number of CMRFs and PWV values.

Results:

Moderate effect size estimates were observed between MetS and PWV (0.68, 95% CI: 0.54–0.82) with a slightly higher effect size for the low-risk compared with the high-risk population group (0.75, 95% CI: 0.58–0.92; and 0.51, 95% CI: 0.32–0.82, respectively). A trend between the number of MetS-related CMRFs and PWV was found with the pooled effect size nearly doubling as the number of MetS-related CMRFs increased, 0.11 (95% CI: 0.04–0.17) for one MetS-related CMRF, 0.26 (95% CI: 0.13–0.4) for two, and 0.4 (95% CI: 0.2–0.6) for three or more.

Conclusion:

These results demonstrated a clinically relevant association between MetS and PWV and an increasing trend in PWV values, such as a MetS-related CMRF increase. Although these results should be considered cautiously because of the considerable heterogeneity, our findings reinforce the rationale of MetS as an aggregation of risk factors with common causes, which could provide additional useful information to guide clinical management.
Effect of frequency and pattern of night shift on hypertension risk in female nurses: a cross-sectional study
Authors: Zhao Bin , Li Jing , Feng Di , Liu Jie , Hao Yuming , Zhen Yanjie , Hao Xiaoran , Liu Fude , Zuo Aifang , Yang Xiulan , Chen Ximin , Jia Rufu , Zhang Ruiqin , Fan Ailing , Wang Yun , Yuan Meijin , Li Bin , Chen Shuling , Cui Jing , Li Xian , Ding Junqin , Zhao Meizhu , Li Laiyou , Li Lanfeng , Yin Xiaohua , Li Yuzhuo , Huang Xianghe , Yu Hongwei , Li Yun , Cui Wei
Published: December 2020

Objectives:

Understanding the effect of night shift on hypertension risk in nurses is important to improve the health of nurses and ensure patient safety. This study aimed to evaluate the effect of the frequency and pattern of night shift on hypertension risk and the interaction of them in female nurses.

Methods:

This cross-sectional study constituted 84 697 female nurses in 13 cities in China. The main contents of the survey included SBP, DBP, the frequency and pattern of night shift, and some other factors that might be associated with hypertension. Logistic regression analyses were used to calculate ORs and 95% CIs to estimate the effect of the frequency and pattern of night shift on hypertension risk and the interaction of them in relation to hypertension risk.

Results:

Having more than 5 to 10 or more than 10 night shifts per month were significantly more likely to be hypertensive (OR 1.19, 95% CI 1.10–1.28; OR 1.32, 95% CI 1.13–1.54), whereas having less than or equal to 5 night shifts per month was not (OR 1.05, 95% CI 0.95–1.16). The patterns of night shift were all associated with a higher probability of hypertension and participants engaging in rapidly rotating night shift had a lower OR (1.14) than those having slowly rotating night shift (1.23) and permanent night shift (1.46). No significant interaction was observed between the frequency and the pattern of night shift (P
interaction = 0.281).

Conclusion:

The frequency and pattern of night shift were associated with hypertension risk in female nurses and no significant interaction was observed between them.
Hemodynamic profiles in treatment-naive arterial hypertension and their clinical implication for treatment choice: an exploratory post hoc analysis
Authors: Glinz Delphine , Bläsi Claudia , Villiger Andrea , Meienberg Andrea , Socrates Thenral , Pfister Otmar , Mayr Michael , Haschke Manuel , Vischer Annina Salome , Burkard Thilo
Published: December 2020

Objective:

Noninvasive thoracic bioimpedance by the HOTMAN System estimates hemodynamic modulators and expresses them as hemodynamic profiles. Aims of this analysis were to describe hemodynamic profiles among treatment-naive hypertensive patients compared with normotensive controls and to investigate whether a hemodynamic-guided choice of therapy improves blood pressure (BP) control within 4 weeks.

Method:

This exploratory post hoc analysis used data of a randomized parallel-group trial including 80 outpatients with newly diagnosed arterial hypertension (AHT), randomized to four antihypertensive first-line monotherapies, and 20 age-matched and sex-matched normotensive controls. Hemodynamic profiles were measured at baseline and after four weeks of treatment. On the basis of the hemodynamic profiles, the most appropriate pharmacological treatment was determined retrospectively and patients were categorised to have received concordant (ConTG) or discordant treatment (DisTG).

Results:

In the hypertensive group, hypervolemia with vasoconstriction was the predominant hemodynamic profile in 48% of patients and hypervolemia without vasoconstriction in 45%, compared with 15 and 50%, respectively, in the control group. After 4 weeks of treatment, the mean (±SD) 24-h BP was 129.9 (±11.0)/81.5 (±8.0) mmHg in the DisTG vs. 133.9 (±12.3)/84.0 (±9.1) mmHg in the ConTG (P = 0.158/0.222). The mean 24-h BP reductions were −9.7 (±10.1)/−5.0 (±6.2) mmHg in the DisTG and −12.4 (±14.8)/−6.9(±6.9) mmHg in the ConTG (P = 0.353/0.223). After 4 weeks of treatment, the BP control rate was 53.7% (43/80) among all, 55.7% (29/52) in the DisTG and 48% (12/25) in the ConTG (P = 0.628).

Conclusion:

Our findings do not support the hypothesis that personalized treatment initiation based on hemodynamic profiles improves BP control in newly diagnosed hypertensive outpatients.
Validity of five formulas in estimating 24-h urinary sodium via spot urine sampling in hypertensive patients living in Northeast China
Authors: Qian Ni , Jiang Yinong , Wang Ying , Yan Peishi , Yao Fumei , Sun Min , Liu Xiaojie , Zhang Ying , Cheng Yunpeng , Lu Yan , Song Wei
Published: December 2020

Objective:

The objective was to evaluate the accuracy of five formulas -- the Kawasaki, Tanaka, INTERSALT, Mage, and Uechi methods -- using spot urinary sampling for 24-h urinary sodium (UNa) prediction in hypertensive patients living in northeast China.

Methods:

There were 1154 hypertensive patients enrolled from multiple centers. Five different formulas were used to predict 24-h UNa excretion via spot morning urinary samples. Actual UNa excretion was measured from 24-h urine samples. The estimated value was compared with the actual value by examining biases, the intraclass correlation coefficients (ICC), and Bland–Altman plots.

Results:

The average excretion of sodium was 2.97 ± 1.26 g/day. The formula-produced mean biases for actual UNa were 0.31 g/day for INTERSALT, 0.80 g/day for Mage, 0.88 g/day for Tanaka, 1.14 g/day for Uechi, and 1.95 g/day for Kawasaki. The ICC was 0.511 for Kawasaki, 0.499 for INTERSALT, 0.468 for Tanaka, 0.402 for Mage, and 0.378 for Uechi. The least mean bias in the lower and moderate salt intake subgroups was 1.22 and 0.07 g/day, respectively, which was calculated using the Mage and INTERSALT methods. The least mean bias in the higher salt intake subgroup was 0.10 g/day for the Uechi method. The INTERSALT method was more efficiency at the individual level, with 17.4% of participants having relative differences within 10%, and 22.3% participants having absolute differences within 393 mg.

Conclusion:

The INTERSALT method may exhibit a good performance in estimating 24-h urinary sodium level for the hypertensive population living in northeast China.
Radiation Mapping for an Unmanned Aerial Vehicle: Development and Simulated Testing of Algorithms for Source Mapping and Navigation Path Generation
Authors: Liu Tairan , Di Fulvio Angela , Chung Long Kiu , Kearfott Kimberlee J.
Published: December 2020

Image reconstruction algorithms were developed for radiation source mapping and used for generating the search path of a moving radiation detector, such as one onboard an unmanned aerial vehicle. Simulations consisted of first assuming radioactive sources of varying complexity and estimating the radiation fields that would then be produced by that source distribution. Next, the “measurements” that would result from a pair of adjacent spatial locations were computed. A crude estimate of the source distribution likely to have produced such “measurements” was reconstructed based upon the limited measurements. Location of the next “measurement” was then determined as halfway between the location of the estimated source and the current “measurement.” With each additional sample, improved source distribution reconstructions were made and used to inform the immediate direction of detector motion. Source reconstruction or mapping was formulated as an inverse problem solved with either maximum a posteriori or least squares (LS) regression deconvolution methods. Different amounts of noise were added to the simulated “measurements,” allowing evaluation of the methods’ performances as functions of signal-to-noise ratio of the measured map. As expected, methods that promote sparsity were better suited in reconstructing point sources. Reliable prior information of the source distribution also improved the reconstruction results, especially with distributed sources. With a non-negative least square algorithm and the suggested paths it generated, location of sources was successfully estimated to an accuracy of 0.014 m within nine iterations in a single-source scenario and 12 iterations in a two-source scenario, given a 10% error on the integrated counts and a Poisson distribution of the noise associated with the measured counts.
THE LOSS OF INFRARED LIGHT SENSITIVITY OF PHOTORECEPTOR CELLS MEASURED WITH TWO-PHOTON EXCITATION AS AN INDICATOR OF DIABETIC RETINOPATHY
Authors: Łabuz Grzegorz , Rayamajhi Asu , Khoramnia Ramin , Palczewska Grażyna , Palczewski Krzysztof , Holschbach Andreas , Auffarth Gerd U.
Published: December 2020

Purpose:

Human photoreceptors are sensitive to infrared light (IR). This sensitivity can be used as a novel indicator of retinal function. Diabetic retinopathy patients were assessed using in vivo two-photon excitation and compared their scotopic IR threshold with that of healthy patients.

Methods:

Sixty-two participants, 28 healthy and 34 with diabetic retinopathy, underwent a comprehensive eye examination, where visual acuity and contrast sensitivity were assessed. Infrared thresholds were measured in the fovea and parafovea following 30-minute dark adaptation. A two-photon excitation device was used with integrated pulsed laser light (1,045 nm) for sensitivity testing and scanning laser ophthalmoscopy for fundus imaging.

Results:

The mean Snellen visual acuity of diabetic patients (6/7.7) was worse than that of the healthy patients (6/5.5), which was significantly different (P < 0.001). Disease patients had decreased contrast sensitivity, especially at 6 and 18 cycles/degree. The mean retinal sensitivity to IR light in eyes with diabetic retinopathy (11.6 ± 2.0 dB) was significantly (P < 0.001) lower than that in normal eyes (15.5 ± 1.3 dB).

Conclusion:

Compared with healthy control subjects, the IR light sensitivity of diabetic patients was significantly impaired. Two-photon measurements can be used in the assessment of retinal disease, but further studies are needed to validate IR light stimulation in various stages of diabetic retinopathy.
FOVEA PLANA ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
Authors: Chatzistergiou Vasileia , Cilliers Helena , Pournaras Jean-Antoine , Ambresin Aude
Published: December 2020

Purpose:

To report on the reliability of optical coherence tomography angiography (OCTA) to diagnose fovea plana.

Methods:

A retrospective, cross-sectional, case–control study included patients with foveal persistence of the inner retinal layers, confirmed by spectral domain OCT, and superficial capillary plexus (SCP) and deep capillary plexus foveal vascularization confirmed by OCTA. A healthy control group was selected. The best-corrected visual acuity was obtained. Spectral-domain OCT was used for measuring the outer nuclear layer thickness, and OCTA determined the foveal avascular zone, SCP, and deep capillary plexus vascular density.

Results:

Optical coherence tomography angiography reliability, based on all parameters, reached 97%, whereas based only on SCP vascular density 91%. The plana group (n = 57) differed significantly from the control group (n = 28) in terms of foveal avascular zone, SCP, and deep capillary plexus foveal vascular density (P < 0.005). Subjects with SCP foveal vascular density >30% or foveal avascular zone <0.1 mm2 had fovea plana. The best-corrected visual acuity of the plana group had no correlation with OCTA quantitative parameters (Pearson |r|<0.18, Spearman |r|<0.44).

Conclusion:

Optical coherence tomography angiography has a high accuracy in diagnosing fovea plana, as its characteristics differ significantly from the normal population. The lack of correlation between the best-corrected visual acuity and OCTA parameters implies that reduced the best-corrected visual acuity is likely to result from coexistent diseases rather than from the foveal structure.
MISALIGNMENT BETWEEN CENTER OF FOVEAL AVASCULAR ZONE AND CENTER OF FOVEAL PHOTORECEPTORS IN EYES WITH IDIOPATHIC EPIRETINAL MEMBRANE
Authors: Hasegawa Taiji , Kawaguchi Ai , Arakawa Hisaya , Maruko Ichiro , Iida Tomohiro
Published: December 2020

Purpose:

To determine the degree of misalignment between the center of foveal avascular zone and the center of foveal photoreceptors in eyes with an idiopathic epiretinal membrane (ERM).

Methods:

We reviewed the medical records of 61 eyes with an idiopathic ERM. A 3 × 3 mm area centered on the fovea was scanned with optical coherence tomography angiography before and at 6 months after surgery. The center of foveal avascular zone and the center of foveal photoreceptors were detected by en-face optical coherence tomography angiography images and sequential optical coherence tomography B-sections in the macular region. The presence or absence of ectopic inner foveal layers was also evaluated.

Results:

The mean distance from the center of foveal photoreceptors to the center of foveal avascular zone was 111.7 ± 106.8 µm in eyes with preoperative ERM. This distance was significantly correlated with the preoperative central foveal thickness (r = 0.33, P = 0.0104). Preoperatively, the ectopic inner foveal layers were present in 27 (44.3%) of 61 eyes. The foveal misalignment was greater in eyes with ectopic inner foveal layers than in those without ectopic inner foveal layers (158.6 ± 140.0 vs. 74.4 ± 45.4 µm, P < 0.0003). At 6 months after ERM surgery, the foveal misalignment was significantly reduced to 73.7 ± 48.0 µm (P = 0.0018).

Conclusion:

Determining the degree of misalignment between the center of foveal avascular zone and the center of foveal photoreceptors might be a useful way to evaluate the degree of ERM traction.
Isavuconazole as Salvage Therapy for Refractory Pediatric Coccidioidal Meningitis
Authors: Naeem Fouzia , Laningham Fred , Kuzmic Brenik , Clerkin Patricia , McCarty James
Published: December 2020

Coccidioidal meningitis remains difficult to treat. The newer triazole, isavuconazole, has demonstrated efficacy in invasive fungal disease with less side effects than other azoles. We describe a case of refractory pediatric coccidioidal meningitis with disease stabilization and improvement on isavuconazole after failing treatment with other antifungal agents.