bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic epilepsies amenable to ketogenic therapies: Indications, contraindications, and underlying mechanisms
Authors: Gavrilovici Cezar , Rho Jong M.
Published: July 2020

Metabolic epilepsies arise in the context of rare inborn errors of metabolism (IEM), notably glucose transporter type 1 deficiency syndrome, succinic semialdehyde dehydrogenase deficiency, pyruvate dehydrogenase complex deficiency, nonketotic hyperglycinemia, and mitochondrial cytopathies. A common feature of these disorders is impaired bioenergetics, which through incompletely defined mechanisms result in a wide spectrum of neurological symptoms, such as epileptic seizures, developmental delay, and movement disorders. The ketogenic diet (KD) has been successfully utilized to treat such conditions to varying degrees. While the mechanisms underlying the clinical efficacy of the KD in IEM remain unclear, it is likely that the proposed heterogeneous targets influenced by the KD work in concert to rectify or ameliorate the downstream negative consequences of genetic mutations affecting key metabolic enzymes and substrates—such as oxidative stress and cell death. These beneficial effects can be broadly grouped into restoration of impaired bioenergetics and synaptic dysfunction, improved redox homeostasis, anti‐inflammatory, and epigenetic activity. Hence, it is conceivable that the KD might prove useful in other metabolic disorders that present with epileptic seizures. At the same time, however, there are notable contraindications to KD use, such as fatty acid oxidation disorders. Clearly, more research is needed to better characterize those metabolic epilepsies that would be amenable to ketogenic therapies, both experimentally and clinically. In the end, the expanded knowledge base will be critical to designing metabolism‐based treatments that can afford greater clinical efficacy and tolerability compared to current KD approaches, and improved long‐term outcomes for patients.
Failure in Systems and Culture: Barriers That Prevent Implementation of Evidence‐Based Fasting Times for Patients in the Acute Care Setting
Authors: Carey Sharon , Hogan Sophie
Published: July 2020

Background

There is strong evidence supporting fasting guidelines of 6 hours’ fast from solids and 2 hours’ fast from fluids prior to surgery. Despite this, patients spend prolonged periods of time fasting for surgery with a lack of research to support translating this evidence into practice, particularly for emergency surgical theater lists. This study aims to explore barriers and enablers to reduce prolonged fasting for patients on emergency surgical lists in the acute care setting.

Methods

Qualitative interviews were undertaken with 22 health professionals on acute surgical wards within a quaternary referral hospital in Sydney, Australia. Semistructured interviews explored barriers and enablers to implementing evidence‐based fasting practices for patients on emergency surgical lists, using a theoretical domains framework. Interviews were transcribed verbatim and analyzed using an inductive thematic approach.

Results

Key barriers to implementing reduced fasting included unpredictable, inflexible systems; cultural concerns; and gaps in knowledge. Major enablers to reducing fasting times are the recognition of patient distress caused by excessive fasting and desire by all 22 interviewees to address the problem.

Conclusions

This research is the first to explore barriers and enablers to implementing interventions to address excessive fasting. This research highlights the complexity of the issue and the need for a multifaceted translational intervention addressing limitations in systems and cultural barriers.
Effect of understaging on local recurrence of rectal cancer
Authors: Giesen Louis J. X. , Borstlap Wernard A. A. , Bemelman Willem A. , Tanis Pieter J. , Verhoef Cornelis , Olthof Pim B. ,   DUTCH SNAPSHOT RESEARCH GROUP
Published: July 2020

Background and Objectives

Magnetic resonance imaging of the pelvis has a limited accuracy to detect positive lymph nodes but does dictate neoadjuvant treatment in rectal cancer. This study aimed to investigate preoperative lymph node understaging and its effects on postoperative local recurrence rate.

Methods

Patients were selected from a retrospective cross‐sectional snapshot study. Patients with emergency surgery, cM1 disease, or unknown cN‐ or (y)pN category were excluded. Clinical and pathologic N‐categories were compared and the impact on local recurrence was determined by multivariable analysis.

Results

Out of 1548 included patients, 233 had preoperatively underestimated lymph node staging based on (y)pN category. Out of the 695 patients staged cN0, 168 (24%) had positive lymph nodes at pathology, and out of the 594 patients staged cN1, 65 (11%) were (y)pN2. Overall 3‐year local recurrence rate was 5%. Clinical N‐category was not associated with local recurrence when corrected for pT‐category, neoadjuvant therapy, and resection margin, neither in patients with (y)pN1 (hazard ratio [HR]: 1.67 (95% confidence interval [CI]: 0.68‐4.12) P = .263) nor (y)pN2‐category (HR: 1.91 95% CI: [0.75‐4.84], P = .175).

Conclusion

Preoperative understaging of nodal status in rectal cancer is not uncommon. No significant effect on local recurrence or overall survival rates were found in the present study.
Statistical characterization of the linear attenuation coefficient in polychromatic CT scans
Authors: Vegas‐Sánchez‐Ferrero Gonzalo , San José Estépar Raúl
Published: July 2020

Purpose

To provide a unifying statistical model that characterizes the integrated x‐ray intensity at the detector after logarithmic transformation and can be extended to the characterization of computed tomography (CT) numbers in the reconstructed image.

Methods

We study the statistical characteristics of polyenergetic x‐ray beams in the detector. Firstly, we consider the characterization of the integrated x‐ray intensity at the detector through a probabilistic model (compound Poisson) that describes its statistics. We analyze its properties and derive the probabilistic distribution after the logarithmic transformation analytically. Finally, we propose a more tractable probabilistic distribution with the same features observed in the characterization, the noncentral Gamma (nc‐Gamma). This distribution exhibits desirable properties for the statistical characterization across the reconstruction process. We assess the assumptions adopted in the derivation of the statistical models throughout Monte Carlo simulations and validate them with a water phantom and a lung phantom acquired in a Siemens clinical CT scan. We evaluate the statistical similarities between the theoretical distribution and the nc‐Gamma using a power analysis with a Kolmogorov–Smirnov test for a 95% confidence level.

Results

The Kolmogorov–Smirnov goodness‐of‐fit test obtained for the Monte Carlo simulation shows an extremely high agreement between the empirical distribution of the post‐logarithmic‐integrated x‐ray intensity and the nc‐Gamma. The experimental validation performed with both phantoms confirmed the excellent match between the theoretical distribution, the proposed nc‐Gamma, and sample distributions in all situations.

Conclusion

We derive an analytical model describing the post‐log distribution of the linear attenuation coefficient in the sensor for polychromatic CT scans. We also demonstrate that the nc‐Gamma distribution approximates well the theoretical distribution. This distribution also approximates well the CT numbers after reconstruction since it naturally extends across linear operations involved in filtered back projection reconstructions. This probabilistic model may provide the analytical foundation to define new likelihood‐based reconstruction methodologies for polychromatic scans.
CT‐based multi‐organ segmentation using a 3D self‐attention U‐net network for pancreatic radiotherapy
Authors: Liu Yingzi , Lei Yang , Fu Yabo , Wang Tonghe , Tang Xiangyang , Jiang Xiaojun , Curran Walter J. , Liu Tian , Patel Pretesh , Yang Xiaofeng
Published: July 2020

Purpose

Segmentation of organs‐at‐risk (OARs) is a weak link in radiotherapeutic treatment planning process because the manual contouring action is labor‐intensive and time‐consuming. This work aimed to develop a deep learning‐based method for rapid and accurate pancreatic multi‐organ segmentation that can expedite the treatment planning process.

Methods

We retrospectively investigated one hundred patients with computed tomography (CT) simulation scanned and contours delineated. Eight OARs including large bowel, small bowel, duodenum, left kidney, right kidney, liver, spinal cord and stomach were the target organs to be segmented. The proposed three‐dimensional (3D) deep attention U‐Net is featured with a deep attention strategy to effectively differentiate multiple organs. Performance of the proposed method was evaluated using six metrics, including Dice similarity coefficient (DSC), sensitivity, specificity, Hausdorff distance 95% (HD95), mean surface distance (MSD) and residual mean square distance (RMSD).

Results

The contours generated by the proposed method closely resemble the ground‐truth manual contours, as evidenced by encouraging quantitative results in terms of DSC, sensitivity, specificity, HD95, MSD and RMSD. For DSC, mean values of 0.91 ± 0.03, 0.89 ± 0.06, 0.86 ± 0.06, 0.95 ± 0.02, 0.95 ± 0.02, 0.96 ± 0.01, 0.87 ± 0.05 and 0.93 ± 0.03 were achieved for large bowel, small bowel, duodenum, left kidney, right kidney, liver, spinal cord and stomach, respectively.

Conclusions

The proposed method could significantly expedite the treatment planning process by rapidly segmenting multiple OARs. The method could potentially be used in pancreatic adaptive radiotherapy to increase dose delivery accuracy and minimize gastrointestinal toxicity.
Comparison of CBCT‐based dose calculation methods in head and neck cancer radiotherapy: from Hounsfield unit to density calibration curve to deep learning
Authors: Barateau Anaïs , De Crevoisier Renaud , Largent Axel , Mylona Eugenia , Perichon Nicolas , Castelli Joël , Chajon Enrique , Acosta Oscar , Simon Antoine , Nunes Jean‐Claude , Lafond Caroline
Published: July 2020

Purpose

Anatomical variations occur during head and neck (H&N) radiotherapy treatment. kV cone‐beam computed tomography (CBCT) images can be used for daily dose monitoring to assess dose variations owing to anatomic changes. Deep learning methods (DLMs) have recently been proposed to generate pseudo‐CT (pCT) from CBCT to perform dose calculation. This study aims to evaluate the accuracy of a DLM and to compare this method with three existing methods of dose calculation from CBCT in H&N cancer radiotherapy.

Methods

Forty‐four patients received VMAT for H&N cancer (70‐63‐56 Gy). For each patient, reference CT (Bigbore, Philips) and CBCT images (XVI, Elekta) were acquired. The DLM was based on a generative adversarial network. The three compared methods were: (a) a method using a density to Hounsfield Unit (HU) relation from phantom CBCT image (HU‐D curve method), (b) a water–air‐bone density assignment method (DAM), and iii) a method using deformable image registration (DIR). The imaging endpoints were the mean absolute error (MAE) and mean error (ME) of HU from pCT and reference CT (CTref). The dosimetric endpoints were dose discrepancies and 3D gamma analyses (local, 2%/2 mm, 30% dose threshold). Dose discrepancies were defined as the mean absolute differences between DVHs calculated from the CTref and pCT of each method.

Results

In the entire body, the MAEs and MEs of the DLM, HU‐D curve method, DAM, and DIR method were 82.4 and 17.1 HU, 266.6 and 208.9 HU, 113.2 and 14.2 HU, and 95.5 and −36.6 HU, respectively. The MAE obtained using the DLM differed significantly from those of other methods (Wilcoxon, P ≤ 0.05). The DLM dose discrepancies were 7 ± 8 cGy (maximum = 44 cGy) for the ipsilateral parotid gland Dmean and 5 ± 6 cGy (max = 26 cGy) for the contralateral parotid gland mean dose (Dmean). For the parotid gland Dmean, no significant dose difference was observed between the DLM and other methods.

The mean 3D gamma pass rate ± standard deviation was 98.1 ± 1.2%, 91.0 ± 5.3%, 97.9 ± 1.6%, and 98.8 ± 0.7% for the DLM, HU‐D method, DAM, and DIR method, respectively. The gamma pass rates and mean gamma results of the HU‐D curve method, DAM, and DIR method differed significantly from those of the DLM.

Conclusions

For H&N radiotherapy, DIR method and DLM appears as the most appealing CBCT‐based dose calculation methods among the four methods in terms of dose accuracy as well as calculation time. Using the DIR method or DLM with CBCT images enables dose monitoring in the parotid glands during the treatment course and may be used to trigger replanning.
Diffusion tensor imaging reveals changes in non‐fat infiltrated muscles in late onset Pompe disease
Authors: Rehmann Robert , Froeling Martijn , Rohm Marlena , Forsting Johannes , Kley Rudolf André , Schmidt‐Wilcke Tobias , Karabul Nesrin , Meyer‐Frießem Christine H. , Vollert Jan , Tegenthoff Martin , Vorgerd Matthias , Schlaffke Lara
Published: July 2020

MRI is a helpful tool for monitoring disease progression in late‐onset Pompe disease (LOPD). Our study aimed to evaluate if muscle diffusion tensor imaging (mDTI) shows alterations in muscles of LOPD patients with <10% fat‐fraction. We evaluated 6 thigh and 7 calf muscles (both legs) of 18 LOPD and 29 healthy controls (HC) with muscle diffusion tensor imaging (mDTI), T1w, and mDixonquant sequences in a 3T MRI scanner. The quantitative mDTI‐values axial diffusivity (λ1), mean diffusivity (MD), radial diffusivity (RD), and fractional anisotropy (FA) as well as fat‐fraction were analyzed. 6‐Minute Walk Test (6‐MWT) data were correlated to diffusion metrics. We found that mDTI showed significant differences between LOPD and HC in diffusion parameters (P < .05). Thigh muscles with <10% fat‐fraction showed significant differences in MD, RD, and λ1‐3. MD positively correlated with 6‐MWT (P = .06). To conclude, mDTI reveals diffusion restrictions in muscles of LOPD with and without fat‐infiltration and reflects structural changes prior to fatty degeneration.
Neuropathy symptom and change: Inotersen treatment of hereditary transthyretin amyloidosis
Authors: Dyck P. James B. , Coelho Teresa , Waddington Cruz Marcia , Brannagan Thomas H. , Khella Sami , Karam Chafic , Berk John L. , Polydefkis Michael J. , Kincaid John C. , Wiesman Janice F. , Litchy William J. , Mauermann Michelle L. , Ackermann Elizabeth J. , Baker Brenda F. , Jung Shiangtung W. , Guthrie Spencer , Pollock Michael , Dyck Peter J.
Published: July 2020

Introduction

Hereditary transthyretin‐mediated amyloidosis (hATTR) manifests as multisystem dysfunction, including progressive polyneuropathy. Inotersen, an antisense oligonucleotide, improved the course of neuropathic impairment in patients with hATTR in the pivotal NEURO‐TTR study (NCT01737398). To determine inotersen's impact on symptoms and patients’ neuropathy experience, we performed a post hoc analysis of the Neuropathy Symptoms and Change (NSC) score.

Methods

Stage 1 or 2 hATTR patients were randomized to receive weekly subcutaneous inotersen or placebo for 65 weeks. NSC score was assessed at baseline and 35 and 66 weeks.

Results

At 66 weeks, inotersen‐treated patients had symptom stabilization as compared with worsening in patients receiving placebo, based on total NSC score. There were also improvements in the subdomains of muscle weakness, sensory, pain, and autonomic symptoms, and for various individual items.

Discussion

Inotersen treatment stabilized neuropathy symptoms, including autonomic symptoms, in patients with hATTR according to NSC score. Thus, the NSC may be an effective measure to assess neuropathy progression and patients’ neuropathy experience in clinical practice.
Material parameter optimization for interior and exterior fluid‐structure acoustic problems
Authors: Ramaswamy Harisankar , Dey Saikat , Oberai Assad A.
Published: July 2020

We present an efficient adjoint‐based framework for computing sensitivities of quantities of interest with respect to material parameters for coupled fluid‐structural acoustic systems with explicit interface coupling. The fluid is modeled using the Helmholtz equation and the structure is modeled using the Navier‐Cauchy equations. Sensitivities are used to drive a gradient based optimization algorithm to solve important problems in structural acoustics, viz noise minimization and vibration isolation. For each problem, we consider two different priors: one where the optimal solution has a smooth variation and another with a bimaterial distribution. These priors are imposed with the help of suitable regularization terms. The effectiveness of this approach is demonstrated on both interior and exterior structural acoustic problems.
Architecture and self‐assembly of the SARS‐CoV‐2 nucleocapsid protein
Authors: Ye Qiaozhen , West Alan M. V. , Silletti Steve , Corbett Kevin D.
Published: July 2020

The COVID‐2019 pandemic is the most severe acute public health threat of the twenty‐first century. To properly address this crisis with both robust testing and novel treatments, we require a deep understanding of the life cycle of the causative agent, the SARS‐CoV‐2 coronavirus. Here, we examine the architecture and self‐assembly properties of the SARS‐CoV‐2 nucleocapsid protein, which packages viral RNA into new virions. We determined a 1.4 Å resolution crystal structure of this protein's N2b domain, revealing a compact, intertwined dimer similar to that of related coronaviruses including SARS‐CoV. While the N2b domain forms a dimer in solution, addition of the C‐terminal spacer B/N3 domain mediates formation of a homotetramer. Using hydrogen‐deuterium exchange mass spectrometry, we find evidence that at least part of this putatively disordered domain is structured, potentially forming an α‐helix that self‐associates and cooperates with the N2b domain to mediate tetramer formation. Finally, we map the locations of amino acid substitutions in the N protein from over 38,000 SARS‐CoV‐2 genome sequences. We find that these substitutions are strongly clustered in the protein's N2a linker domain, and that substitutions within the N1b and N2b domains cluster away from their functional RNA binding and dimerization interfaces. Overall, this work reveals the architecture and self‐assembly properties of a key protein in the SARS‐CoV‐2 life cycle, with implications for both drug design and antibody‐based testing.
Testicular volume in non‐obstructive azoospermia with a history of bilateral cryptorchidism may predict successful sperm retrieval by testicular sperm extraction
Authors: Osaka Akiyoshi , Iwahata Toshiyuki , Kobori Yoshitomo , Shimomura Yukihito , Yoshikawa Naoki , Onota Shin , Yamamoto Atsushi , Ide Hisamitsu , Sugimoto Kouhei , Okada Hiroshi
Published: July 2020

Purpose

Cryptorchidism is one of the most common causes of non‐obstructive azoospermia (NOA) in adulthood. Even if early orchidopexy is performed to preserve fertility potential, some patients still suffer from azoospermia. Fertility potential is significantly lower in bilateral than unilateral cryptorchidism. The aims of this study were to identify clinical parameters that predict the likely success of sperm recovery by microscopic testicular sperm extraction (micro‐TESE) and also the likely outcome of intracytoplasmic sperm injection using sperm from NOA patients who submitted to bilateral orchidopexy.

Methods

Fifty‐two NOA patients with a history of bilateral cryptorchidism underwent micro‐TESE. The following clinical parameters were evaluated as predictive factors for successful sperm recovery: age at micro‐TESE; age at orchidopexy; period from orchidopexy to micro‐TESE; luteinizing hormone (LH); follicle‐stimulating hormone (FSH); testosterone; average testicular volume; and body mass index.

Results

In the successful sperm retrieval group, average testicular volume was significantly greater, while serum LH and FSH, and body mass index were significantly lower. In a multivariate analysis, average testicular volume was positively correlated with successful sperm recovery.

Conclusion

Our results indicate that testicular volume in NOA patients with bilateral cryptorchidism is a predictor for successful sperm recovery.
Adsorption of sarin and chlorosarin onto the Al12N12 and Al12P12 nanoclusters: DFT and TDDFT calculations
Authors: Sedighi Sima , Baei Mohammad T. , Javan Masoud , Ince Joshua Charles , Soltani Alireza , Jokar Mohammad Hassan , Tavassoli Samaneh
Published: July 2020

This study provides details of the electronic and optical structures and binding energies of sarin (SF) and chlorosarin (SC) with Al–N and Al–P surfaces of Al12N12 and Al12P12 nanoclusters in the gas phase. The adsorption mechanism of SF and SC on these nanoclusters containing the Al3+ central cation was studied. Optimized geometries and thermodynamic parameters of SF and SC adsorption complexes were calculated. SF and SC are chemisorbed on these nanoclusters because of the formation of PO···Al bonds. The chemical bond is formed between an oxygen atom of SF and SC and an aluminum atom of fullerene‐likes (chemisorption). However, the binding energies of the complexes with the Al12N12 nanocluster are larger than these values for the Al12P12 nanocluster. The interaction enthalpy and Gibbs free energy of all studied systems were found to be negative. We can conclude that SF and SC will be adsorbed preferably on Al12N12 nanocluster.
Oxycodone injections not paired with conditioned place preference have little effect on the hippocampal opioid system in female and male rats
Authors: Ashirova Elina , Contoreggi Natalina H. , Johnson Megan A. , Al‐Khayat Fatima J. , Calcano Gabriela A. , Rubin Batsheva R. , O’Cinneide Emma M. , Zhang Yong , Zhou Yan , Gregoire Lennox , McEwen Bruce S. , Kreek Mary Jeanne , Milner Teresa A.
Published: July 2020

Oxycodone (Oxy) conditioned place preference (CPP) in Sprague Dawley rats results in sex‐specific alterations in hippocampal opioid circuits in a manner that facilitates opioid‐associative learning processes, particularly in females. Here, we examined if Oxy (3 mg/kg, I.P.) or saline (Sal) injections not paired with behavioral testing similarly affect the hippocampal opioid system. Sal‐injected females compared to Sal‐injected males had: (1) higher densities of cytoplasmic delta opioid receptors (DOR) in GABAergic hilar dendrites suggesting higher baseline reserve DOR pools and (2) elevated phosphorylated DOR levels, but lower phosphorylated mu opioid receptor (MOR) levels in CA3a suggesting that the baseline pools of activated opioid receptors vary in females and males. In contrast to CPP studies, Oxy‐injections in the absence of behavioral tests resulted in few changes in the hippocampal opioid system in either females or males. Specifically, Oxy‐injected males compared to Sal‐injected males had fewer DORs near the plasma membrane of CA3 pyramidal cell dendrites and in CA3 dendritic spines contacted by mossy fibers, and lower pMOR levels in CA3a. Oxy‐injected females compared to Sal‐injected females had higher total DORs in GABAergic dendrites and lower total MORs in parvalbumin‐containing dendrites. Thus, unlike Oxy CPP, Oxy‐injections redistributed opioid receptors in hippocampal neurons in a manner that would either decrease (males) or not alter (females) excitability and plasticity processes. These results indicate that the majority of changes within hippocampal opioid circuits that would promote opioid‐associative learning processes in both females and males do not occur with Oxy administration alone, and instead must be paired with CPP.
Activated carbon column adsorption of compounds that mimic urban stormwater dissolved organic nitrogen
Authors: Mohtadi Mehrdad , James Bruce R. , Davis Allen P.
Published: July 2020

Nutrients mobilized by stormwater can exacerbate eutrophication in receiving waters. While bioretention systems are increasingly employed to improve stormwater quality, they do not normally incorporate design attributes for removal of dissolved organic nitrogen (DON). Thus, the current study concentrated on continuous column adsorption of stormwater DON using a media mixture of coal activated carbon and quartz sand. Adsorption of eight model organic nitrogenous compounds was studied and only pyrrole showed an appreciable adsorption performance; other organic nitrogen compounds were weakly adsorbed. The breakthrough depth for pyrrole was 88 m (equivalent to 4.4 m simulated rainfall depth), at a superficial velocity of 61 cm/hr and influent DON concentration of 1 mg N/L. Subsequent experiments revealed that adsorption of pyrrole was minimally affected by superficial velocity, such that its DON removal efficiency was greater than 91% for all tested superficial velocities (7–489 cm/hr). Accordingly, adsorption processes may be employed for removing stormwater DON fractions behaving similarly to pyrrole; data suggest DON removal initially at greater than 95%, gradually falling to 30% through 25 years of service.

Practitioner points

Adsorption of eight different organic nitrogenous compounds onto coal‐based activated carbon was investigated.

Amino acids and an amino sugar were weakly adsorbed onto the activated carbon.

Pyrrole, a moderately hydrophobic heterocyclic organic nitrogen compound was effectively adsorbed.

A 30‐cm depth was considered as adequate for removal of pyrrole and compounds that would similarly adsorb.

Evidence of biological ammonification was present in all studies except for pyrrole.
A comparison of thyroidal protection by stable iodine or perchlorate in the case of acute or prolonged radioiodine exposure
Authors: Eder Stefan , Hermann Cornelius , Lamkowski Andreas , Kinoshita Manabu , Yamamoto Tetsuo , Abend Michael , Shinomiya Nariyoshi , Port Matthias , Rump Alexis
Published: July 2020

In the case of a nuclear power plant accident, repetitive/prolonged radioiodine release may occur. Radioiodine accumulates in the thyroid and by irradiation enhances the risk of cancer. Large doses of non-radioactive iodine may protect the thyroid by inhibiting radioiodine uptake into the gland (iodine blockade). Protection is based on a competition at the active carrier site in the cellular membrane and the Wolff–Chaikoff effect, the latter being, however, only transient (24–48 h). Perchlorate may alternatively provide protection by a carrier competition mechanism only. Perchlorate has, however, a stronger affinity to the carrier than iodide. Based on an established biokinetic–dosimetric model developed to study iodine blockade, and after its extension to describe perchlorate pharmacokinetics and the inhibition of iodine transport through the carrier, we computed the protective efficacies that can be achieved by stable iodine or perchlorate in the case of an acute or prolonged radioiodine exposure. In the case of acute radioiodine exposure, perchlorate is less potent than stable iodine considering its ED50. A dose of 100 mg stable iodine has roughly the same protective efficacy as 1000 mg perchlorate. For prolonged exposures, single doses of protective agents, whether stable iodine or perchlorate, offer substantially lower protection than after acute radioiodine exposure, and thus repetitive administrations seem necessary. In case of prolonged exposure, the higher affinity of perchlorate for the carrier in combination with the fading Wolff–Chaikoff effect of iodine confers perchlorate a higher protective efficacy compared to stable iodine. Taking into account the frequency and seriousness of adverse effects, iodine and perchlorate at equieffective dosages seem to be alternatives in case of short-term acute radioiodine exposure, whereas preference should be given to perchlorate in view of its higher protective efficacy in the case of longer lasting radioiodine exposures.
Prehabilitation in Frail Surgical Patients: A Systematic Review
Authors: Baimas‐George Maria , Watson Michael , Elhage Sharbel , Parala‐Metz Armida , Vrochides Dionisios , Davis Bradley R.
Published: July 2020

Background

Frailty is a customized marker of biological age that helps to gauge an individual's functional physiologic reserve and ability to react to stress and is associated with increased postoperative morbidity and mortality. In order to mitigate frailty preoperatively, the concept of prehabilitation has entered the forefront which encompasses multidisciplinary interventions to improve health and lessen the incidence of postoperative decline. The purpose of this study is to investigate the impact of prehabilitation on postoperative outcomes in frail, surgical patients.

Methods

A comprehensive literature search was performed by two independent researchers according to PRISMA guidelines. Inclusion criteria were (1) a randomized controlled trial, case–control or observational study; (2) prehabilitation intervention; (3) frailty assessment; and (4) surgical intervention.

Results

There were five articles included in the review. Evaluation of these articles demonstrated prehabilitation may improve operative outcomes in frail surgical patients. There were no assessments as to whether prehabilitation was cost‐effective although it was feasible. Prehabilitation programs should include elements of exercise, nutrition, and psychosocial counseling. Frailty should be assessed with a validated index in surgical patients who may undergo prehabilitation.

Conclusion

Prehabilitation in frail surgical patients may be the appropriate process through which providers can lessen operative risk. Currently, however, there is little evidence supporting the use of prehabilitation in this population with only five studies identified in this systematic review. More randomized controlled trials are clearly needed.
A very rare case of an accessory subscapularis muscle and its potential clinical significance
Authors: Zielinska Nicol , Olewnik Łukasz , Karauda Piotr , Tubbs R. Shane , Polguj Michał
Published: July 2020

The subscapularis muscle is the largest muscle of the rotator cuff and its main function is internal rotation. It is morphologically variable in both point of origin and insertion. The presence of an accessory subscapularis muscle can lead to brachial plexus neuropathy. This report presents a very rare accessory subscapularis muscle originating from two distinct bands on the subscapularis and teres major muscles. The insertion was divided among four tendons. The fourth tendon is bifurcated. One of these was connected to the tendon of the subscapularis muscle and the other three inserted into the base of the coracoid process of the scapula. This anomalous muscle has the potential to entrap the nerves of the posterior cord such as the axillary, lower subscapular, and thoracodorsal nerves.
Scanning PIV of turbulent flows over and through rough porous beds using refractive index matching
Authors: Rousseau Gauthier , Ancey Christophe
Published: July 2020

This paper presents image velocimetry measurements on turbulent flows adjacent to a permeable bed made of randomly packed glass particles. For measuring flow velocities inside the bed, the refractive index of the glass particles was matched with that of the fluid. By continuously scanning in the transverse direction, we measured the streamwise and vertical velocity components within a three-dimensional domain (3D2C-PIV), including first- and second-order turbulent statistics. We established how the scanning travel speed is associated with the laser sheet thickness and the space-time velocity fluctuations for collecting reliable measurements. The methodology was applied to free-surface flows over a sloping bed under low relative submergence and supercritical conditions. Space- and time-averaged profiles were obtained in a representative elementary volume as defined by thedouble-averagingprocedure (Nikora et al. in J Hydraulic Eng.127(2):123–133, 2001). A turbulent boundary layer over the rough bed was observed when experiments were run at intermediate Reynolds numbers Re =$$O(1000)$$O(1000). Apart from measuring subsurface velocities, this method shed light on the part played by the rough bed in the overall flow dynamics: the roughness layer was a buffer region within which porosity varied sharply and turbulent stress was rapidly dampened.

Graphic abstract
Auditory DUM neurons in a bush-cricket: inhibited inhibitors
Authors: Stumpner Andreas , Gubert Silvia , Knorr Debbra Y. , Göpfert Martin C.
Published: July 2020

Thoracic ganglia of many hearing insects house the first level of auditory processing. In bush-crickets, the largest population of local auditory neurons in the prothoracic processing centre are dorsal unpaired median (DUM) neurons. It has been suggested that DUM neurons are inhibitory using γ-aminobutyric acid (GABA) as transmitter. Immunohistochemistry reveals a population of about 35–50 GABA-positive somata in the posterior medial cluster of the prothoracic ganglion. Only very few small somata in this cluster remain unstained. At least 10 neurites from 10 neurons can be identified. Intracellularly stained auditory DUM neurons have their soma in the cluster of median GABA positive cells and most of them exhibit GABA-immunoreactivity. Responses of certain DUM neurons show obvious signs of inhibition. Application of picrotoxin (PTX), a chloride-channel blocker in insects, changes the responses of many DUM neurons. They become broader in frequency tuning and broader or narrower in temporal pattern tuning. Furthermore, inhibitory postsynaptic potentials (IPSPs) may be replaced by excitatory postsynaptic potentials. Loss of an IPSP in the rising graded potential after PTX-application leads to a significant reduction of first-spike latency. Therefore, auditory DUM neurons receive effective inhibition and are the best candidates for inhibition in DUM neurons and other auditory interneurons.
Body surface rewarming in fully and partially hypothermic king penguins
Authors: Lewden Agnès , Nord Andreas , Bonnet Batshéva , Chauvet Florent , Ancel André , McCafferty Dominic J.
Published: July 2020

Penguins face a major thermal transition when returning to land in a hypothermic state after a foraging trip. Uninsulated appendages (flippers and feet) could provide flexible heat exchange during subsequent rewarming. Here, we tested the hypothesis that peripheral vasodilation could be delayed during this recovery stage. To this end, we designed an experiment to examine patterns of surface rewarming in fully hypothermic (the cloaca and peripheral regions (here; flippers, feet and the breast) < 37 °C) and partially hypothermic (cloaca at normothermia ≥ 37 °C, but periphery at hypothermia) king penguins (Aptenodytes patagonicus) when they rewarmed in the laboratory. Both groups rewarmed during the 21 min observation period, but the temperature changes were larger in fully than in partially hypothermic birds. Moreover, we observed a 5 min delay of peripheral temperature in fully compared to partially hypothermic birds, suggesting that this process was impacted by low internal temperature. To investigate whether our laboratory data were applicable to field conditions, we also recorded surface temperatures of free-ranging penguins after they came ashore to the colony. Initial surface temperatures were lower in these birds compared to in those that rewarmed in the laboratory, and changed less over a comparable period of time on land. This could be explained both by environmental conditions and possible handling-induced thermogenesis in the laboratory. Nevertheless, this study demonstrated that appendage vasodilation is flexibly used during rewarming and that recovery may be influenced by both internal temperature and environmental conditions when penguins transition from sea to land.
Intoxicated persons showing challenging behavior demand complexity interventions: a pilot study at the interface of the ER and the complexity intervention unit
Authors: Verheesen Stefan M. H. , ten Doesschate Freek , van Schijndel Maarten A. , van der Gaag Rutger Jan , Cahn Wiepke , van Waarde Jeroen A.
Published: July 2020

Intoxicated persons showing challenging behavior (IPCBs) under influence of alcohol and/or drugs frequently have trouble finding appropriate acute care. Often IPCBs are stigmatized being unwilling or unable to accept help. Separated physical and mental healthcare systems hamper integrated acute care for IPCBs. This pilot aimed to substantiate the physical, psychiatric, and social health needs of IPCBs visiting the emergency room (ER) during a 3-month period. All ER visits were screened. After triage by the ER physician, indicated IPCBs were additionally assessed by the consultation–liaison–psychiatry physician. If needed, IPCBs were admitted to a complexity intervention unit for further examinations to provide integrated treatments and appropriate follow-up care. The INTERMED and Health of the Nation Outcome Scale (HoNOS) questionnaires were used to substantiate the complexity and needs. Field-relevant stakeholders were interviewed about this approach for acute integrated care. Alongside substance abuse, almost half of identified IPCBs suffered from comorbid psychiatric disturbances and one third showed substantial physical conditions requiring immediate medical intervention. Almost all IPCBs (96%) accepted the acute medical care voluntarily. IPCBs showed high mean initial scores of INTERMED (27.8 ± 10.0) and HoNOS (20.8 ± 6.9). At discharge from the complexity intervention unit, the mean HoNOS score decreased significantly (13.4 ± 8.6; P < 0.001). Field-relevant stakeholders strongly supported the interdisciplinary approach and ER-facility for IPCBs and acknowledged their unmet health needs. A biopsychosocial assessment at the ER, followed by a short admission if necessary, is effective in IPCBs. This approach helps to merge separated healthcare systems and may reduce stigmatization of IPCBs needing help.
Behr syndrome and hypertrophic cardiomyopathy in a family with a novel UCHL1 deletion
Authors: McMacken Grace , Lochmüller Hanns , Bansagi Boglarka , Pyle Angela , Lochmüller Angela , Chinnery Patrick F. , Laurie Steve , Beltran Sergi , Matalonga Leslie , Horvath Rita
Published: July 2020

Background

Behr syndrome is a clinically distinct, but genetically heterogeneous disorder characterized by optic atrophy, progressive spastic paraparesis, and motor neuropathy often associated with ataxia. The molecular diagnosis is based on gene panel testing or whole-exome/genome sequencing.

Methods

Here, we report the clinical presentation of two siblings with a novel genetic form of Behr syndrome. We performed whole-exome sequencing in the two patients and their mother.

Results

Both patients had a childhood-onset, slowly progressive disease resembling Behr syndrome, starting with visual impairment, followed by progressive spasticity, weakness, and atrophy of the lower legs and ataxia. They also developed scoliosis, leading to respiratory problems. In their late 30’s, both siblings developed a hypertrophic cardiomyopathy and died of sudden cardiac death at age 43 and 40, respectively. Whole-exome sequencing identified the novel homozygous c.627_629del; p.(Gly210del) deletion in UCHL1.

Conclusions

The presentation of our patients raises the possibility that hypertrophic cardiomyopathy may be an additional feature of the clinical syndrome associated with UCHL1 mutations, and highlights the importance of cardiac follow-up and treatment in neurodegenerative disease associated with UCHL1 mutations.
Nonlinear multiscale simulation of instabilities due to growth of an elastic film on a microstructured substrate
Authors: Valizadeh Iman , Weeger Oliver
Published: July 2020

The objective of this contribution is the numerical investigation of growth-induced instabilities of an elastic film on a microstructured soft substrate. A nonlinear multiscale simulation framework is developed based on the FE2 method, and numerical results are compared against simplified analytical approaches, which are also derived. Living tissues like brain, skin, and airways are often bilayered structures, consisting of a growing film on a substrate. Their modeling is of particular interest in understanding biological phenomena such as brain development and dysfunction. While in similar studies the substrate is assumed as a homogeneous material, this contribution considers the heterogeneity of the substrate and studies the effect of microstructure on the instabilities of a growing film. The computational approach is based on the mechanical modeling of finite deformation growth using a multiplicative decomposition of the deformation gradient into elastic and growth parts. Within the nonlinear, concurrent multiscale finite element framework, on the macroscale a nonlinear eigenvalue analysis is utilized to capture the occurrence of instabilities and corresponding folding patterns. The microstructure of the substrate is considered within the large deformation regime, and various unit cell topologies and parameters are studied to investigate the influence of the microstructure of the substrate on the macroscopic instabilities. Furthermore, an analytical approach is developed based on Airy’s stress function and Hashin–Shtrikman bounds. The wavelengths and critical growth factors from the analytical solution are compared with numerical results. In addition, the folding patterns are examined for two-phase microstructures and the influence of the parameters of the unit cell on the folding pattern is studied.
Characterization of the dual problem of linear matrix inequality for H-infinity output feedback control problem via facial reduction
Authors: Waki Hayato , Sebe Noboru
Published: July 2020

This paper deals with the minimization of $$H_\infty $$

H
∞

output feedback control. This minimization can be formulated as a linear matrix inequality (LMI) problem via a result of Iwasaki and Skelton 1994. The strict feasibility of the dual problem of such an LMI problem is a valuable property to guarantee the existence of an optimal solution of the LMI problem. If this property fails, then the LMI problem may not have any optimal solutions. Even if one can compute parameters of controllers from a computed solution of the LMI problem, then the computed $$H_\infty $$

H
∞

norm may be very sensitive to a small change of parameters in the controller. In other words, the non-strict feasibility of the dual tells us that the considered design problem may be poorly formulated. We reveal that the strict feasibility of the dual is closely related to invariant zeros of the given generalized plant. The facial reduction is useful in analyzing the relationship. The facial reduction is an iterative algorithm to convert a non-strictly feasible problem into a strictly feasible one. We also show that facial reduction spends only one iteration for so-called regular $$H_\infty $$

H
∞

output feedback control. In particular, we can obtain a strictly feasible problem by using null vectors associated with some invariant zeros. This reduction is more straightforward than the direct application of facial reduction.
Factors associated with subsequent surgical procedures after intramedullary nailing for tibial shaft fractures
Authors: Hendrickx Laurent A. M. , Virgin James , Doornberg Job N. , Kerkhoffs Gino M. M. J. , Jaarsma Ruurd L.
Published: July 2020

Introduction

The reported rate of subsequent surgery after intramedullary nailing (IMN) of tibial shaft fractures (TSFs) is as high as 21%. However, most studies have not included the removal of symptomatic implant in these rates. The purpose of this study was to evaluate the subsequent surgery rate after IMN of TSFs, including the removal of symptomatic implants. Secondly, this study aimed to assess what factors are associated with subsequent surgery (1) to promote fracture and wound healing and (2) for the removal of symptomatic implants.

Methods

One-hundred and ninety-one patients treated with IMN for TSFs were retrospectively included. The rate of subsequent surgery was determined. Bi- and multivariable analysis was used to identify variables associated with subsequent surgery.

Results

Approximately half of patients (46%) underwent at least one subsequent surgical procedure. Forty-eight (25%) underwent a subsequent surgical procedure to promote fracture or wound healing. Age (P < 0.01), multi-trauma (P < 0.01), open fracture (P < 0.001) and index surgery during weekdays (P < 0.05) were associated with these procedures. Thirty-nine patients (20%) underwent a subsequent surgical procedure for removal of symptomatic implants. There was a significantly lower rate of implant removal in ASA II (11%) and ASA III–IV (14%) patients compared to ASA I patients (29%) (P < 0.05).

Conclusions

Patients treated with IMN for TSFs should be consented that about one-in-two patients will undergo an additional surgical procedure. Half of these procedures are required to promote wound or fracture healing; the other half are for symptomatic implant removal.

Level of evidence

Therapeutic level-IV.
Recent developments in carbon-based two-dimensional materials: synthesis and modification aspects for electrochemical sensors
Authors: Kirchner Eva-Maria , Hirsch Thomas
Published: July 2020

This review (162 references) focuses on two-dimensional carbon materials, which include graphene as well as its allotropes varying in size, number of layers, and defects, for their application in electrochemical sensors. Many preparation methods are known to yield two-dimensional carbon materials which are often simply addressed as graphene, but which show huge variations in their physical and chemical properties and therefore on their sensing performance. The first section briefly reviews the most promising as well as the latest achievements in graphene synthesis based on growth and delamination techniques, such as chemical vapor deposition, liquid phase exfoliation via sonication or mechanical forces, as well as oxidative procedures ranging from chemical to electrochemical exfoliation. Two-dimensional carbon materials are highly attractive to be integrated in a wide field of sensing applications. Here, graphene is examined as recognition layer in electrochemical sensors like field-effect transistors, chemiresistors, impedance-based devices as well as voltammetric and amperometric sensors. The sensor performance is evaluated from the material’s perspective of view and revealed the impact of structure and defects of the 2D carbon materials in different transducing technologies. It is concluded that the performance of 2D carbon-based sensors is strongly related to the preparation method in combination with the electrical transduction technique. Future perspectives address challenges to transfer 2D carbon-based sensors from the lab to the market.
First report of a new corneal pathogen: Phaeoacremonium parasiticum
Authors: Massa Horace , Riat Arnaud , Panos Georgios D.
Published: July 2020

Keratitis is a public health issue in developing countries and a potentially sight-threatening condition. Collagen fibrils in the corneal stroma are parallels to each other. Fundamental substance maintains the same space between collagen fibrils. That is how corneal transparency can be achieved. Any damage which can modify this structure will lead to corneal opacity and loss of vision. Fungal keratitis might appear in up to one-third of cases. Nevertheless, fungal keratitis remains poorly described and understood. Herein, we present the first ever reported case of corneal infection due to Phaeoacremonium parasiticum in a young patient. We describe the clinical and microbial characteristics, and we also discuss the use of confocal microscopy in early diagnosis of this infection.