Benchmarking and integrating human B-cell receptor genomic and antibody proteomic profiling.

Immunoglobulins (Ig), which exist either as B-cell receptors (BCR) on the surface of B cells or as antibodies when secreted, play a key role in the recognition and response to antigenic threats. The capability to jointly characterize the BCR and antibody repertoire is crucial for understanding human adaptive immunity. From peripheral blood, bulk BCR sequencing (bulkBCR-seq) currently provides the highest sampling depth, single-cell BCR sequencing (scBCR-seq) allows for paired chain characterization, and antibody peptide sequencing by tandem mass spectrometry (Ab-seq) provides information on the composition of secreted antibodies in the serum.

The multi-specific V-based Humabody CB213 co-targets PD1 and LAG3 on T cells to promote anti-tumour activity.

Background: Improving cancer immunotherapy long-term clinical benefit is a major priority. It has become apparent that multiple axes of immune suppression restrain the capacity of T cells to provide anti-tumour activity including signalling through PD1/PD-L1 and LAG3/MHC-II.

Methods: CB213 has been developed as a fully human PD1/LAG3 co-targeting multi-specific Humabody composed of linked V domains that avidly bind and block PD1 and LAG3 on dual-positive T cells.

Evidence-based impact by clinical engineers on global patients outcomes.

The intersection of technological changes and societal evolution has transformed every aspect of human life. Technological advancements are transforming how healthcare knowledge is expanding and accelerating the outreach of critical medical services delivery (Jamal et al. in Health Information Management Journal 38(3):26-37, 2009).

Mathematical modeling of clinical engineering approach to evaluate the quality of patient care.

At present, the patient care delivery system (PCDS) in a hospital/medical institute/clinic is absolutely medical technology-dependent and this tendency is found to increase day by day. To ensure the quality of patient care (QPC) appropriate implementation of the patient care technology management system (PCTMS) is necessary. Unfortunately, it is found to be absent in the healthcare delivery system in most of the countries in the world.

Cofilin-1 phosphorylation catalyzed by ERK1/2 alters cardiac actin dynamics in dilated cardiomyopathy caused by lamin A/C gene mutation.

Hyper-activation of extracellular signal-regulated kinase (ERK) 1/2 contributes to heart dysfunction in cardiomyopathy caused by mutations in the lamin A/C gene (LMNA cardiomyopathy). The mechanism of how this affects cardiac function is unknown. We show that active phosphorylated ERK1/2 directly binds to and catalyzes the phosphorylation of the actin depolymerizing factor cofilin-1 on Thr25.

Attitudes and Practices Related to Clinical Alarms: A Follow-up Survey.

Background: Alarm fatigue is a widely acknowledged patient safety concern in hospitals. In 2013, The Joint Commission issued a National Patient Safety Goal on Alarm Management, making addressing alarm management a priority. To capture changes in attitudes and practices related to alarms, the Healthcare Technology Foundation conducted and reported findings from national online surveys in 2006 and 2011 and completed a third survey in 2016.

Actions from head to toe: An update on Bone/Body Morphogenetic Proteins in health and disease.

The pleiotropic actions of Bone Morphogenetic Proteins in many different tissues has led us to the conclusion that they may be viewed as Body Morphogenetic Proteins (BMPs). This is supported by a broad range of distinct BMP-related diseases. Here, we summarize highlights from the 10th international BMP conference, which took place from September 16th to 20th 2014 in Berlin.

Structural insights into BMP receptors: Specificity, activation and inhibition.

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β family (TGFβ), which signal through hetero-tetrameric complexes of type I and type II receptors. In humans there are many more TGFβ ligands than receptors, leading to the question of how particular ligands can initiate specific signaling responses. Here we review structural features of the ligands and receptors that contribute to this specificity.

Nurses' Perspectives on Clinical Alarms.

Background: Alarm hazards are a critical issue in patient safety. Of all health care providers, nurses are the ones most directly affected by the multitude of clinical alarms.

Objectives: To qualitatively explore nurses' experiences with clinical alarms.

Structure of the fibrillin-1 N-terminal domains suggests that heparan sulfate regulates the early stages of microfibril assembly.

The human extracellular matrix glycoprotein fibrillin-1 is the primary component of the 10- to 12-nm-diameter microfibrils, which perform key structural and regulatory roles in connective tissues. Relatively little is known about the molecular mechanisms of fibrillin assembly into microfibrils. Studies using recombinant fibrillin fragments indicate that an interaction between the N- and C-terminal regions drives head-to-tail assembly.

¹H, ¹³C and ¹⁵N resonance assignments for the fibrillin-1 EGF2-EGF3-hybrid1-cbEGF1 four-domain fragment.

Fibrillins are large extracellular glycoproteins that form the principal component of microfibrils. These perform a vital structural function in the extracellular matrix of many tissues. Fibrillins have also been implicated in mediating a number of protein-protein interactions, some of which may be significant in regulating growth factors such as transforming growth factor β.

¹H, ¹³C and ¹⁵N assignments of the four N-terminal domains of human fibrillin-1.

Fibrillins are extracellular, disulphide-rich glycoproteins that form 10-12 nm diameter microfibrils in connective tissues. They are found in the majority of higher animals, from jellyfish to humans. Fibrillin microfibrils confer properties of elasticity and strength on connective tissue and regulate growth factor availability in the extracellular matrix (ECM).

Defining the limits of single-molecule FRET resolution in TIRF microscopy.

Single-molecule FRET (smFRET) has long been used as a molecular ruler for the study of biology on the nanoscale (∼2-10 nm); smFRET in total-internal reflection fluorescence (TIRF) Förster resonance energy transfer (TIRF-FRET) microscopy allows multiple biomolecules to be simultaneously studied with high temporal and spatial resolution. To operate at the limits of resolution of the technique, it is essential to investigate and rigorously quantify the major sources of noise and error; we used theoretical predictions, simulations, advanced image analysis, and detailed characterization of DNA standards to quantify the limits of TIRF-FRET resolution. We present a theoretical description of the major sources of noise, which was in excellent agreement with results for short-timescale smFRET measurements (<200 ms) on individual molecules (as opposed to measurements on an ensemble of single molecules).

Computer-controlled electrical stimulation for quantitative mapping of human cortical function.

Cortical mapping with electrical stimulation (ES) in neurosurgical patients typically involves the manually controlled delivery of suprathreshold electrical current to a discrete area of the brain. Limited numbers of trials and imprecise current delivery methods increase the variability of the behavioral response and make it difficult to collect quantitative mapping data, which is especially important in research studies of human cortical function. To overcome these limitations, the authors developed a method for computer-controlled delivery of defined electrical current to implanted intracranial electrodes.

A national online survey on the effectiveness of clinical alarms.

Purpose: To develop a national online survey to be administered by the American College of Clinical Engineers Healthcare Technology Foundation to hospitals and healthcare workers to determine the problems associated with alarms in hospitals.

Methods: An online survey was developed by a 16-member task force representing professionals from clinical engineering, nursing, and technology to evaluate the reasons health-care workers do not respond to clinical alarms.

Results: A total of 1327 persons responded to the survey; most (94%) worked in acute care hospitals.

Issues associated with off label use of medical devices.

Off label use as applied to medical devices is the application of the device for a purpose that is not included as an indication in the FDA and EC approved device labeling. Such applications are also called unapproved or new uses. Beyond a use not being indicated, some off label uses may be expressly contraindicated as well as explicitly warned against.

Benchmarking clinical engineering program.

Professional labor shortage in healthcare delivery system and specifically the management of staffing effectiveness in clinical engineering field are recent developments where shortage of comparative information exist and almost no information on its impact on performance outcomes. We attempted over the past few years to define and measure optimal application of manpower to medical technology management in the hospital setting.

Risk assessment - hospital view in selecting medical technology.

Appropriate deployment of technological innovation contributes to improvement in the quality of healthcare delivered, the containment of cost, and access to the healthcare system. Hospitals have been allocating a significant portion of their resources to procuring and managing capital assets; they are continuously faced with demands for new medical equipment and are asked to manage existing inventory for which they are not well prepared. To objectively direct their investment, hospitals are developing medical technology management programs that need pertinent information and planning methodology for integrating new equipment into existing operations as well as for mitigating patient safety issues and costs of ownership.

TeleHealth: operational issues to consider.

Recent developments in the telecommunications and the information technology fields hold the promise of improved access to and better utilization of an integrated health care related resources. In addition, to these developments, the deployment of interactive distant training programs offer an opportunity to decrease the knowledge gap between the leading academic medical centers where new medical expertise is continuously being discovered and remote health care practitioners who find themselves pressed to deliver quality care that meets the needs of their communities in a competitive environment of limited resources.

Calcium regulates scallop muscle by changing myosin flexibility.

Muscle myosins are molecular motors that convert the chemical free energy available from ATP hydrolysis into mechanical displacement of actin filaments, bringing about muscle contraction. Myosin cross-bridges exert force on actin filaments during a cycle of attached and detached states that are coupled to each round of ATP hydrolysis. Contraction and ATPase activity of the striated adductor muscle of scallop is controlled by calcium ion binding to myosin.

Safe use of cellular telephones in hospitals: fundamental principles and case studies.

Many industries and individuals have embraced cellular telephones. They provide mobile, synchronous communication, which could hypothetically increase the efficiency and safety of inpatient healthcare. However, reports of early analog cellular telephones interfering with critical life-support machines had led many hospitals to strictly prohibit cellular telephones.