Development of high titer anti-drug antibodies in a Phase 1b/2a infant clesrovimab trial are associated with RSV exposure beyond day 150.

Background: Clesrovimab is a human half-life extended mAb in phase 3 evaluation for the prevention of RSV disease in infants. ADA were observed at late time points in a phase 1b/2a study where clesrovimab was well tolerated with an extended half-life of ∼45 days.

Methods: Serum samples at days 150, 365 and 545 post-dose were assayed for ADA titers.

Analysis of the first genetic engineering attribution challenge.

The ability to identify the designer of engineered biological sequences-termed genetic engineering attribution (GEA)-would help ensure due credit for biotechnological innovation, while holding designers accountable to the communities they affect. Here, we present the results of the first Genetic Engineering Attribution Challenge, a public data-science competition to advance GEA techniques. Top-scoring teams dramatically outperformed previous models at identifying the true lab-of-origin of engineered plasmid sequences, including an increase in top-1 and top-10 accuracy of 10 percentage points.

Dataset of five years of and satellite derived chlorophyll concentrations and its spatiotemporal variability in the Rotorua Te Arawa Lakes, New Zealand.

Horizontal patchiness of water quality attributes in lakes substantially influences the ability to accurately determine an average condition of a lake from traditional in situ sampling. Monitoring programmes for lake water quality often rely on water samples from one or few locations but the assumption of representativeness is seldomly tested. Satellite observations can support environmental monitoring by detecting horizontal variability of water quality attributes over entire lakes.

Evaluating Use Cases for Human Challenge Trials in Accelerating SARS-CoV-2 Vaccine Development.

Human challenge trials (HCTs) have been proposed as a means to accelerate SARS-CoV-2 vaccine development. We identify and discuss 3 potential use cases of HCTs in the current pandemic: evaluating efficacy, converging on correlates of protection, and improving understanding of pathogenesis and the human immune response. We outline the limitations of HCTs and find that HCTs are likely to be most useful for vaccine candidates currently in preclinical stages of development.

Analysis of regulatory guidance on antidrug antibody testing for therapeutic protein products.

Therapeutic proteins have the potential to induce unwanted immune responses. The potential impact of immunogenicity on pharmacokinetics, pharmacodynamics, safety and efficacy are well established. Here, we analyze key aspects of current US FDA and EMA guidelines on the development and validation of antidrug antibody assays.

Development and Prospective Validation of a Machine Learning-Based Risk of Readmission Model in a Large Military Hospital.

Background: Thirty-day hospital readmissions are a quality metric for health care systems. Predictive models aim to identify patients likely to readmit to more effectively target preventive strategies. Many risk of readmission models have been developed on retrospective data, but prospective validation of readmission models is rare.

Tonic-clonic seizure detection using accelerometry-based wearable sensors: A prospective, video-EEG controlled study.

Purpose: The aim of this prospective, video-electroencephalography (video-EEG) controlled study was to evaluate the performance of an accelerometry-based wearable system to detect tonic-clonic seizures (TCSs) and to investigate the accuracy of different seizure detection algorithms using separate training and test data sets.

Methods: Seventy-five epilepsy surgery candidates undergoing video-EEG monitoring were included. The patients wore one three-axis accelerometer on each wrist during video-EEG.

CLAss-Specific Subspace Kernel Representations and Adaptive Margin Slack Minimization for Large Scale Classification.

In kernel-based classification models, given limited computational power and storage capacity, operations over the full kernel matrix becomes prohibitive. In this paper, we propose a new supervised learning framework using kernel models for sequential data processing. The framework is based on two components that both aim at enhancing the classification capability with a subset selection scheme.

Microwave technology for detecting traumatic intracranial bleedings: tests on phantom of subdural hematoma and numerical simulations.

Traumatic brain injury is the leading cause of death and severe disability for young people and a major public health problem for elderly. Many patients with intracranial bleeding are treated too late, because they initially show no symptoms of severe injury and are not transported to a trauma center. There is a need for a method to detect intracranial bleedings in the prehospital setting.

The effects of ventricular drainage on the intracranial pressure signal and the pressure reactivity index.

In subarachnoid hemorrhage (SAH) patients intracranial pressure (ICP) is usually monitored via an extraventricular drain (EVD), which can produce false readings when the drain is open. It is established that both the ICP cardiac pulse frequency and long term trends over several hours are often seriously corrupted. The aim of this study was to establish whether or not the intermediate frequency bands [respiratory, Mayer wave and very low frequency (VLF)] were also corrupted.

Microwave-based stroke diagnosis making global prehospital thrombolytic treatment possible.

Here, we present two different brain diagnostic devices based on microwave technology and the associated two first proof-of-principle measurements that show that the systems can differentiate hemorrhagic from ischemic stroke in acute stroke patients, as well as differentiate hemorrhagic patients from healthy volunteers. The system was based on microwave scattering measurements with an antenna system worn on the head. Measurement data were analyzed with a machine-learning algorithm that is based on training using data from patients with a known condition.

An optimal frequency range for assessing the pressure reactivity index in patients with traumatic brain injury.

The objective of this study was to identify the optimal frequency range for computing the pressure reactivity index (PRx). PRx is a clinical method for assessing cerebral pressure autoregulation based on the correlation of spontaneous variations of arterial blood pressure (ABP) and intracranial pressure (ICP). Our hypothesis was that optimizing the methodology for computing PRx in this way could produce a more stable, reliable and clinically useful index of autoregulation status.

Microwave technology for localization of traumatic intracranial bleedings-a numerical simulation study.

Traumatic brain injury (TBI) is a major public health problem worldwide. Intracranial bleedings represents the most serious complication of TBI and need to be surgically evacuated promptly to save lives and mitigate injury. Microwave technology (MWT) is promising as a complement to computed tomography (CT) to be used in road and air ambulances for early detection of intracranial bleedings.

The design of a medical school social justice curriculum.

The acquisition of skills to recognize and redress adverse social determinants of disease is an important component of undergraduate medical education. In this article, the authors justify and define "social justice curriculum" and then describe the medical school social justice curriculum designed by the multidisciplinary Social Justice Vertical Integration Group (SJVIG) at the Geisel School of Medicine at Dartmouth. The SJVIG addressed five goals: (1) to define core competencies in social justice education, (2) to identify key topics that a social justice curriculum should cover, (3) to assess social justice curricula at other institutions, (4) to catalog institutionally affiliated community outreach sites at which teaching could be paired with hands-on service work, and (5) to provide examples of the integration of social justice teaching into the core (i.

A multidimensional signal processing approach for classification of microwave measurements with application to stroke type diagnosis.

A multidimensional signal processing method is described for detection of bleeding stroke based on microwave measurements from an antenna array placed around the head of the patient. The method is data driven and the algorithm uses samples from a healthy control group to calculate the feature used for classification. The feature is derived using a tensor approach and the higher order singular value decomposition is a key component.

Plateau waves and baroreflex sensitivity in patients with head injury: a case study.

The study aimed to investigate baroreceptor reflex sensitivity in a patient with head injury for whom plateau waves of intracranial pressure (ICP) were recorded. Baroreflex sensitivity index was separately estimated on top of plateau waves and during intermediate intervals between two consecutive waves. The EuroBaVar data set was utilized to verify and validate the results.

Cerebrovascular mechanical properties and slow waves of intracranial pressure in TBI patients.

Myogenic autoregulation of cerebral blood flow is one of the mechanisms affecting cerebral hemodynamics. Short or long-lasting changes in intracranial pressure (ICP) are believed to reveal the responses of the cerebral system to myogenic stimuli. Through the incorporation of a theoretical model into the experimental measurements of cerebrovascular distensibility and compliance in patients with traumatic brain injury (TBI), the current study is an attempt to explain ICP dynamics in either presence or absence of cerebral autoregulation.

Pulse wave velocity in patients with severe head injury a pilot study.

The study aimed to determine the potential of pulse wave velocity measurements to reflect changes in compliant cerebral arteries/arterioles in head injured patients. The approach utilizes the electrocardiogram and intracranial pressure signals to measure the wave transit time between heart and cranial cavity. Thirty five clinical records of nineteen head injured patients, with different levels of cerebrovascular pressure-reactivity response, were investigated through the study.

Purification process development of a recombinant monoclonal antibody expressed in glycoengineered Pichia pastoris.

A robust and scalable purification process was developed to quickly generate antibody of high purity and sufficient quantity from glycoengineered Pichia pastoris fermentation. Protein A affinity chromatography was used to capture the antibody from fermentation supernatant. A pH gradient elution was applied to the Protein A column to prevent antibody precipitation at low pH.

A detailed analysis of level I evidence (randomized controlled trials and meta-analyses) in five plastic surgery journals to date: 1978 to 2009.

Background: Evidence-based medicine is the synthesis of clinical expertise, best available clinical evidence, and patient values to provide optimal health outcomes. A scant number of randomized controlled trials exist in the plastic surgery literature. The authors sought to analyze the level I studies (randomized controlled trials and meta-analyses) in five leading plastic surgery journals to date to understand the distribution of primary categories of study, primary outcomes, age breakdown, degree of quality, and the trend in publication rates.

An employer-based, pharmacist intervention model for patients with type 2 diabetes.

Purpose: Changes in glycosylated hemoglobin (HbA(1c)) levels, blood pressure measurements, and utilization metrics among diabetic patients managed by a clinical pharmacist were studied.

Summary: This pharmacist intervention model was developed by Polk County, Florida, to engage patients with diabetes in managing their health based on the Asheville Project's framework. The diabetes program was implemented in February 2005, with an on-site clinical pharmacist to counsel participants with diabetes.

Normalized power transmission between ABP and ICP in TBI.

A new approach to study the pulse transmission between the cerebrovascular bed and the intracranial space is presented. In the proposed approach, the normalized power transmission between ABP and ICP has got the main attention rather than the actual power transmission. Evaluating the gain of the proposed transfer function at any single frequency can reveal how the percentage of contribution of that specific frequency component has been changed through the cerebrospinal system.

Varying forage type, metabolizable protein concentration, and carbohydrate source affects manure excretion, manure ammonia, and nitrogen metabolism of dairy cows.

Effects of forage source, concentration of metabolizable protein (MP), and type of carbohydrate on manure excretion by dairy cows and production of ammonia from that manure were evaluated using a central composite experimental design. All diets (dry basis) contained 50% forage that ranged from 25:75 to 75:25 alfalfa silage:corn silage. Diets contained 10.

Impact of methionine oxidation on the binding of human IgG1 to Fc Rn and Fc gamma receptors.

Methionine oxidation commonly occurs in the Fc fragment of therapeutic monoclonal antibodies; however, its impact on antibody function has not been addressed. Using surface plasmon resonance and cell binding assays, we examined the impact of methionine oxidation on the binding of two humanized IgG1 antibodies to Fc gamma receptors (Fc gammaR) and to the neonatal Fc receptor (Fc Rn). A panel of Fc gammaRs, including Fc gammaRI, Fc gammaRIIa-131H, Fc gammaRIIa-131R, Fc gammaRIIb/c, Fc gammaRIII ALF, Fc gammaRIII ALV, and Fc gammaRIIIb was evaluated.