Clinical Importance of Binaural Information: Extending Auditory Assessment in Clinical Populations Using a Portable Testing Platform.

Purpose The purpose of this study is to use variability on tests of basic auditory processing to allow identification of those tests that could be used clinically to describe functional hearing ability beyond the pure-tone audiogram and clinical speech-in-noise tests. Method Psychoacoustic tests implemented using the Portable Automated Rapid Testing system on a calibrated iPad were evaluated for nine young normal-hearing participants (M age = 21.3, SD = 2.5) and seven hearing-impaired participants (M age = 64.9, SD = 13.5). Participants completed 10 psychoacoustic subtests in a quiet room. Correlational analyses were used to compare performance on the psychoacoustic test battery with performance on a clinical speech-in-noise test and with the 4-frequency pure-tone average (4FreqPTA). Results Spectral processing ability was highly correlated with 4FreqPTA, and temporal processing ability showed minimal variability across the hearing-impaired group. Tests involving binaural processing captured variability across hearing-impaired listeners not associated with 4FreqPTA or speech-in-noise performance. Conclusions Tests that capture the ability to use binaural cues may add information to what current clinical protocols reveal about patients with auditory complaints. Further testing with a larger sample size is needed to confirm the need for binaural measurements and to develop normative data for clinical settings.

Proton beam quality enhancement by spectral phase control of a PW-class laser system.

We report on experimental investigations of proton acceleration from solid foils irradiated with PW-class laser-pulses, where highest proton cut-off energies were achieved for temporal pulse parameters that varied significantly from those of an ideally Fourier transform limited (FTL) pulse. Controlled spectral phase modulation of the driver laser by means of an acousto-optic programmable dispersive filter enabled us to manipulate the temporal shape of the last picoseconds around the main pulse and to study the effect on proton acceleration from thin foil targets. The results show that applying positive third order dispersion values to short pulses is favourable for proton acceleration and can lead to maximum energies of 70 MeV in target normal direction at 18 J laser energy for thin plastic foils, significantly enhancing the maximum energy compared to ideally compressed FTL pulses. The paper further proves the robustness and applicability of this enhancement effect for the use of different target materials and thicknesses as well as laser energy and temporal intensity contrast settings. We demonstrate that application relevant proton beam quality was reliably achieved over many months of operation with appropriate control of spectral phase and temporal contrast conditions using a state-of-the-art high-repetition rate PW laser system.

Managing Food Allergy in Schools During the COVID-19 Pandemic.

In the wake of the COVID-19 pandemic and massive disruptions to daily life in the spring of 2020, in May 2020, the Centers for Disease Control (CDC) released guidance recommendations for schools regarding how to have students attend while adhering to principles of how to reduce the risk of contracting SARS-CoV-2. As part of physical distancing measures, the CDC is recommending that schools who traditionally have had students eat in a cafeteria or common large space instead have children eat their lunch or other meals in the classroom at already physically distanced desks. This has sparked concern for the safety of food-allergic children attending school, and some question of how the new CDC recommendations can coexist with recommendations in the 2013 CDC Voluntary Guidelines on Managing Food Allergy in Schools as well as accommodations that students may be afforded through disability law that may have previously prohibited eating in the classroom. This expert consensus explores the issues related to evidence-based management of food allergy at school, the issues of managing the health of children attending school that are acutely posed by the constraints of an infectious pandemic, and how to harmonize these needs so that all children can attend school with minimal risk from both an infectious and allergic standpoint.

Prosthetic gait of unilateral lower-limb amputees with current and novel prostheses: A pilot study.

BACKGROUND: Novel lower-limb prostheses aim to improve the quality of locomotion of individuals with an amputation. This study evaluates the biomechanics of a novel bionic foot during walking. METHODS: Able-bodied individuals (n = 7) and individuals with a transfemoral (n = 6) or transtibial amputation (n = 6) were included. Able-bodied individuals conducted one experimental trial, whereas individuals with transtibial and transfemoral amputations conducted a familiarization (with current prosthesis) and two experimental trials using a passive and bionic prosthesis. Each trial consisted of 3 bouts of 2 min of treadmill walking at different speeds. Biomechanical data were gathered using a force platform and motion capture system and analysed using Statistical Parametric Mapping and (non)-parametric tests. FINDINGS: Conventional prosthetic feet alter gait patterns and induce locomotion difficulties. While walking at a normal speed with the passive prosthesis, transtibial amputees display reduced maximum heel forces, increased ankle and trunk angular velocities at midstance, and increased knee angle during stance and swing phases on their effected side (P ≤ 0.026). Improved lower-limb kinematics was demonstrated during slow and normal speed walking with the bionic prosthesis; however, dynamic trunk stability was negatively impacted during this condition. The bionic prosthesis did not benefit transfemoral amputees at any walking speed. INTERPRETATION: Transtibial amputees can better approximate typical movement patterns at slow and normal walking speeds using the novel bionic prosthesis; however the same benefit was not observed in transfemoral amputees.

Demonstration of a beam loaded nanocoulomb-class laser wakefield accelerator.

Laser-plasma wakefield accelerators have seen tremendous progress, now capable of producing quasi-monoenergetic electron beams in the GeV energy range with few-femtoseconds bunch duration. Scaling these accelerators to the nanocoulomb range would yield hundreds of kiloamperes peak current and stimulate the next generation of radiation sources covering high-field THz, high-brightness X-ray and γ-ray sources, compact free-electron lasers and laboratory-size beam-driven plasma accelerators. However, accelerators generating such currents operate in the beam loading regime where the accelerating field is strongly modified by the self-fields of the injected bunch, potentially deteriorating key beam parameters. Here we demonstrate that, if appropriately controlled, the beam loading effect can be employed to improve the accelerator's performance. Self-truncated ionization injection enables loading of unprecedented charges of ∼0.5 nC within a mono-energetic peak. As the energy balance is reached, we show that the accelerator operates at the theoretically predicted optimal loading condition and the final energy spread is minimized.Higher beam quality and stability are desired in laser-plasma accelerators for their applications in compact light sources. Here the authors demonstrate in laser plasma wakefield electron acceleration that the beam loading effect can be employed to improve beam quality by controlling the beam charge.

Epstein-Barr virus-associated gastric cancer reveals intratumoral heterogeneity of PIK3CA mutations.

Background: Recent whole-genome sequencing identified four molecular subtypes of gastric cancer (GC), of which the subgroup of Epstein-Barr virus-associated GC (EBVaGC) showed a significant enrichment of PIK3CA mutations. We here aimed to validate independently the enrichment of PIK3CA mutations in EBVaGC of a Central European GC cohort, to correlate EBV status with clinico-pathological patient characteristics and to test for a major issue of GC, intratumoral heterogeneity. Patients and methods: In a first step, 484 GCs were screened for EBV and PIK3CA hot spot mutations of exon 9/20 using EBER in situ hybridization and pyrosequencing, respectively. Secondly, an extended sequencing of PIK3CA also utilizing next generation sequencing was carried out in all EBVaGCs and 96 corresponding lymph node metastases. Results: Twenty-two GCs were EBER-positive, all being of latency type I. Intratumoral heterogeneity of EBER-positivity was found in 18% of EBVaGCs. Twenty-three GCs held PIK3CA mutations in hot spot regions of exon 9 or 20, being significantly more common in EBVaGCs (P < 0.001). Subsequent extended sequencing of PIK3CA of EBVaGCs showed that 14% harvested three to five different PIK3CA genotypes (including wildtype) in the same primary tumor, albeit in histologically and spatially distinct tumor areas, and that intratumoral heterogeneity of PIK3CA was also present in the corresponding lymph node metastases. Conclusions: Our findings unravel issues of tumor heterogeneity and illustrate that the assessment of the EBV status in tissue biopsies might carry the risk of sampling errors, which may significantly hamper adequate molecular tumor classification in a more clinical setting. Moreover, this is the first report of intratumoral heterogeneity of PIK3CA mutations in GC, and our findings lead to the conclusion that PIK3CA mutant and -wildtype tumor subclones are skilled to metastasize independently to different regional lymph nodes.

Transplacental transmission of Neospora caninum in moose (Alces alces).

A 5-years-old moose (Alces alces) cow kept in a zoo in the German Federal State of Brandenburg aborted a female foetus of 44cm crown rump length (CRL). Pathohistological analysis revealed several Neospora (N.) caninum infected cells and cysts, as well as multifocal gliosis, necrosis, haemorrhages, dystrophic mineralisation and haemosiderosis in the brain, predominantly in cerebrum and brainstem. In addition, mild lymphocytic meningitis was present. Together with the fresh foetus, a mummified foetus of 16cm CRL was expelled. Neither focal necrosis, nor inflammation was detected in the brain of the mummified foetus. By two polymerase chain reactions (PCR) targeting the pNc5 gene of N. caninum (i.e. an end point PCR and a real-time PCR), by two serological methods (immunofluorescence test and immunoblot), by histological and immunohistochemical analyses, transplacental N. caninum infection was confirmed in the fresh foetus and interpreted as possible cause of abortion. Infection with other agents causing abortion including Bovine Herpesvirus 1 (BHV1), Bluetongue Virus (BTV), Bovine Virus Diarrhoea Virus (BVDV), Brucella spp., Chlamydia spp., Coxiella burnetii and Toxoplasma gondii were excluded. Our findings show that control measures may be necessary to protect captive moose against accidental N. caninum infection. Further studies are needed to explore the importance of neosporosis in wild and captive moose.

Conducting an Oral Food Challenge to Peanut in an Infant.

Results from the Learning Early About Peanut trial and its follow-up study suggest that early peanut introduction in the diets of high-risk infants may prevent the development of peanut allergy. Allergy organizations around the world released a unified statement, the Consensus Communication on Early Peanut Introduction and the Prevention of Peanut Allergy in High Risk Infants, in response to results from the Learning Early About Peanut trial, which recommends early introduction of peanut into the diet of those children at greatest risk of development of peanut allergy. As a result, it is expected that practicing allergists will experience an increased demand to perform an oral food challenge (OFC) in infants. Allergists often perform OFCs; however, conducting an OFC in an infant creates unique circumstances that have not been considered in previously published OFC guideline documents. The purpose of this workgroup report is to provide guidance to practitioners regarding the proper approach for conducting a peanut challenge in an infant.

Dental enamel defects in German medieval and early-modern-age populations.

SUMMARY: Aim of this study was to investigate the frequency and type of developmental defects of enamel (DDE) in a medieval and an early-modern-age population from Thuringia, Germany. Sixty-six skeletons subdivided into 31 single burials (12th/13th c.) and 35 individuals buried in groups (15th/16th c.) were examined. DDE were classified on 1,246 teeth according to the DDE index. Molar-incisor-hypomineralisation (MIH), a special type of DDE, was recorded according to the European Academy of Paediatric Dentistry (EAPD) criteria. DDE was found in 89.4% of the individuals (single burials 90.3% and group burials 88.6%). Hypoplastic pits were the most frequent defect in primary teeth and linear enamel hypoplasia (LEH) in permanent teeth. 13 individuals (24.1%) showed at least one hypomineralised permanent tooth, 12.2% had MIH on at least one first permanent molar and 10.0% in permanent incisors. Second primary molars were affected in 8.0% of the children and juveniles. No individual suffered from affected molars and incisors in combination. Endogenous factors like nutritional deficiencies and health problems in early childhood could have been aetiological reasons of DDE and MIH. The frequency of DDE and MIH might have been masked by extended carious lesions, dental wear and ante-mortem tooth loss.

Randomized comparison of the safety of Flublok(®) versus licensed inactivated influenza vaccine in healthy, medically stable adults ≥ 50 years of age.

BACKGROUND: The safety and tolerability of Flublok(®), a purified recombinant hemagglutinin seasonal influenza vaccine, was compared to AFLURIA(®) in a randomized, blinded clinical trial in adults ≥ 50 years of age with attention to hypersensitivity reactions. METHODS: This blinded, randomized trial of healthy adults ≥ 50 years of age compared safety of Flublok vs. AFLURIA with respect to pre-specified possible hypersensitivity: "rash," "urticaria," "swelling" and "non-dependent edema;" solicited reactogenicity and unsolicited adverse events. Subject-reported outcomes were collected for 30 days after vaccination. All adverse event terms were reviewed by physicians blinded to vaccine group, who added other terms possibly reflecting hypersensitivity. Case records of subjects with possible hypersensitivity were adjudicated by independent experts blinded to treatment assignment to identify likely hypersensitivity reactions. Non-inferiority of the incidence of hypersensitivity in the two vaccine groups was pre-defined as an absolute difference with an upper bound of 2-sided 95% confidence limits ≤ 0.015. RESULTS: A total of 2640 subjects were enrolled, evenly split in age cohorts of 50-64 and ≥ 65 years. Fifty-two subjects reported at least one term possibly representing hypersensitivity, with a slight imbalance of 31 on Flublok and 21 on AFLURIA. The adjudicators determined that six and four subjects on Flublok and AFLURIA, respectively, likely met clinical criteria for hypersensitivity, yielding a difference in incidence between the two vaccine groups of 0.15% (upper bound of 2-sided 95% CI=0.9%). Reactogenicity and overall adverse event profiles were similar across both vaccines. CONCLUSIONS: Flublok was non-inferior to AFLURIA in adults ≥ 50 years of age with respect to expert-adjudicated events of likely hypersensitivity during 30 days following vaccination (Sponsored by Protein Sciences Corporation; ClinicalTrials.gov number NCT01825200).

What if you stretch the IFU? A mechanical insight into stent graft Instructions For Use in angulated proximal aneurysm necks.

Endovascular treatment for patients with a proximal neck anatomy outside instructions for use is an ongoing topic of debate in endovascular aneurysm repair. This paper employs the finite element method to offer insight into possible adverse effects of deploying a stent graft into an angulated geometry. The effect of angulation, straight neck length and device oversize was investigated in a full factorial parametric analysis. Stent apposition, area reduction of the graft, asymmetry of contact forces and the ability to find a good seal were investigated. Most adverse effects are expected for combinations of high angulation and short straight landing zones. Higher oversize has a beneficiary effect, but not enough to compensate the adverse effects of (very) short and angulated angles. Our analysis shows that for an angle between the suprarenal aorta and proximal neck above 60°, proximal kinking of the device can occur. The method used offers a engineering view on the morphological limits of EVAR for a clinically used device.

Food allergy: a practice parameter update-2014.

This parameter was developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma & Immunology (JCAAI). The AAAAI and the ACAAI have jointly accepted responsibility for establishing "Food Allergy: A practice parameter update-2014." This is a complete and comprehensive document at the current time. The medical environment is a changing one, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, ACAAI, and JCAAI. These parameters are not designed for use by pharmaceutical companies in drug promotion.

The influence of vascular anatomy on carotid artery stenting: a parametric study for damage assessment.

Carotid artery stenting is emerging as an alternative technique to surgery for the treatment of symptomatic severe carotid stenosis. Clinical and experimental evidence demonstrates that both plaque morphology and biomechanical changes due to the device implantation can be possible causes of an unsuccessful treatment. In order to gain further insights of the endovascular intervention, a virtual environment based on structural finite element simulations was built to emulate the stenting procedure on generalized atherosclerotic carotid geometries which included a damage model to quantify the injury of the vessel. Five possible lesion scenarios were simulated by changing both material properties and vascular geometrical features to cover both presumed vulnerable and stable plaques. The results were analyzed with respect to lumen gain and wall stresses which are potentially related to the failure of the procedure according to previous studies. Our findings show that an elliptic lumen shape and a thinner fibrous cap with an underlying lipid pool result in higher stenosis reduction, while large calcifications and fibrotic tissue are more prone to recoil. The shielding effect of a thicker fibrous cap helps to reduce local compressive stresses in the soft plaque. The presence of a soft plaque reduces the damage in the healthy vascular structures. Contrarily, the presence of hard plaque promotes less damage volume in the fibrous cap and reduces stress peaks in this region, but they seem to increase stresses in the media-intima layer. Finally the reliability of the achieved results was put into clinical perspective.

Filling the void: a coalescent numerical and experimental technique to determine aortic stent graft mechanics.

The presented study details a combined experimental and computational method to assess and compare the mechanical behavior of the main body of 4 different stent graft designs. The mechanical response to a flat plate compression and radial crimping of the devices is derived and related to geometrical and material features of different stent designs. The finite element modeling procedure is used to complement the experimental results and conduct a solution sensitivity study. Finite element evaluations of the mechanical behavior match well with experimental findings and are used as a quantitative basis to discuss design characteristics of the different devices.

Virtual evaluation of stent graft deployment: a validated modeling and simulation study.

The presented study details the virtual deployment of a bifurcated stent graft (Medtronic Talent) in an Abdominal Aortic Aneurysm model, using the finite element method. The entire deployment procedure is modeled, with the stent graft being crimped and bent according to the vessel geometry, and subsequently released. The finite element results are validated in vitro with placement of the device in a silicone mock aneurysm, using high resolution CT scans to evaluate the result. The presented work confirms the capability of finite element computer simulations to predict the deformed configuration after endovascular aneurysm repair (EVAR). These simulations can be used to quantify mechanical parameters, such as neck dilations, radial forces and stresses in the device, that are difficult or impossible to obtain from medical imaging.

Our capricious vessels: The influence of stent design and vessel geometry on the mechanics of intracranial aneurysm stent deployment.

There is a growing interest in virtual tools to assist clinicians in evaluating different procedures and devices for endovascular treatment. In the present study we use finite element analysis to investigate the influence of stent design and vessel geometry for stent assisted coiling of intracranial aneurysms. Nine virtual stenting procedures were performed: three nitinol stent designs ((i) an open cell stent resembling the Neuroform, (ii) a generic stiff and (iii) a more flexible closed cell design), were deployed in three patient-specific cerebral aneurysmatic vessels. We investigated the percentage of strut area covering the aneurysm neck, the straightening induced on the cerebrovasculature by the stent placement (quantified by the reduction in tortuosity), and stent apposition to the wall (quantified as the percentage of struts within 0.2mm of the vessel). The results suggest that the open cell design better covers the aneurysm neck (11.0±1.1%) compared to both the stiff (7.8±1.6%) and flexible (8.7±1.6%) closed cell stents, and induces less straightening of the vessel (-5.1±1.6% vs. -42.9±9.8% and -26.9±11.9% ). The open cell design has, however, less struts apposing well to the vessel wall (56.0±6.4%) compared to the flexible (73.4±4.6%) and stiff (70.4±5.1%) closed cell design. With the presented study, we hope to contribute to and improve aneurysm treatment, using a novel patient specific environment as a possible pre-operative tool to evaluate mechanical stent behavior in different vascular geometries.