Temporal dynamics of in vitro hemostatic function in platelets cryopreserved using a novel approach for rapid issuance.

BACKGROUND: Current procedures for thawing and issuing of cryopreserved platelets (CPPs) are laborious and have remained challenging in emergency settings such as blood banks and military operations. In this prospective study, a novel processing method designed to facilitate the rapid issuance of CPPs with no postthaw handling required was developed and functionally characterized in parallel with standard CPPs manufactured. STUDY DESIGN AND METHODS: Double-dose plateletpheresis units (n = 42) were cryopreserved at -80°C in 5%-6% dimethyl sulfoxide to produce matched pairs thawed successively over a 27-month period for comparison between two processing arms. In contrast to the standard CPPs manufactured as standalone units, platelets were frozen in tandem with resuspending plasma in a distinct partition as a single unit in the novel method, herein referred to as tandem CPPs. Postthaw (PT) CPPs from both arms were assessed at PT0-, 12-, and 24-h to measure platelet recovery, R-time (time to clot initiation; min), and maximum amplitude (MA; clot strength; mm) using thromboelastography. RESULTS: In the overall dataset, mean platelet recovery was higher (p < .0005) for tandem CPPs (83.9%) compared with standard CPPs (73.3%) at PT0; mean R-times were faster (p < .0005) for tandem CPPs (2.5-3.6 min) compared with standard CPPs (3.0-3.8 min); mean MA was higher for tandem CPPs (57.8-59.5 mm) compared with standard CPPs (52.1-55.8 mm) at each postthaw time point (p < .05). CONCLUSION: Robust temporal dynamics of superior hemostatic functionality were established for tandem CPPs over extended cryopreservation up to 27 months and 24 h of postthaw storage.

Water splitting with silicon p-i-n superlattices suspended in solution.

Photoelectrochemical (PEC) water splitting to produce hydrogen fuel was first reported 50 years ago1, yet artificial photosynthesis has not become a widespread technology. Although planar Si solar cells have become a ubiquitous electrical energy source economically competitive with fossil fuels, analogous PEC devices have not been realized, and standard Si p-type/n-type (p-n) junctions cannot be used for water splitting because the bandgap precludes the generation of the needed photovoltage. An alternative paradigm, the particle suspension reactor (PSR), forgoes the rigid design in favour of individual PEC particles suspended in solution, a potentially low-cost option compared with planar systems2,3. Here we report Si-based PSRs by synthesizing high-photovoltage multijunction Si nanowires (SiNWs) that are co-functionalized to catalytically split water. By encoding a p-type-intrinsic-n-type (p-i-n) superlattice within single SiNWs, tunable photovoltages exceeding 10 V were observed under 1 sun illumination. Spatioselective photoelectrodeposition of oxygen and hydrogen evolution co-catalysts enabled water splitting at infrared wavelengths up to approximately 1,050 nm, with the efficiency and spectral dependence of hydrogen generation dictated by the photonic characteristics of the sub-wavelength-diameter SiNWs. Although initial energy conversion efficiencies are low, multijunction SiNWs bring the photonic advantages of a tunable, mesoscale geometry and the material advantages of Si-including the small bandgap and economies of scale-to the PSR design, providing a new approach for water-splitting reactors.

Dissecting the complexity of pediatric blood transfusions and risk of adverse reactions in Aotearoa New Zealand.

BACKGROUND: Children have different clinical and physiological drivers for transfusion from adult recipients. However, adverse transfusion reactions (ATRs) in pediatric patients are usually reported using the same criteria as for adults. Broad assessments of pediatric ATRs neglect substantial variation in different developmental stages. MATERIALS AND METHODS: This retrospective study included 342,950 patients, ~2.43 million transfusions, and 5,540 ATR reports collated from New Zealand hospitals between 2005 and 2021. Using 16 years as the upper age limit, 138,856 pediatric transfusions and 402 pediatric ATR reports were identified and dissected at three levels: pediatric as a whole, pediatric developmental stage (i.e., neonate, infant, preschool, and school), and chronological age to identify patients at high risk of ATRs. Multivariate logistic regression analysis was followed to quantify risk factors. RESULTS: Pediatric recipients had a higher ATR risk than adults (p=6.9-07) but the high risk was associated mainly with children older than 2 years. Neonates and infants accounted for 75.0% of pediatric recipients but had much lower ATR rates than adults. Pediatric transfusion recipients showed a clear male bias prior to age 11 years and then a female bias. However, gender difference in experiencing ATRs was significant only after age 13 years (p=2.3-04). Analyses focusing on the high-risk group revealed allergic reactions being the cause of the elevated risk and identified the main risk factors of number of transfusions (p=4.5-10) and multiple types of components transfused (p=2.0-13). DISCUSSION: The identified ATR risk factors signal linkage with the biological drivers for transfusion. Low ATR rates in infancy could also be attributed to use of neonatal components, low transfusions per patient, and less developed immunity. The relative increase in female recipients from age 11 may be associated with increased red blood cell demand following puberty.

A pilot randomized clinical trial of cryopreserved versus liquid-stored platelet transfusion for bleeding in cardiac surgery: The cryopreserved versus liquid platelet-New Zealand pilot trial.

BACKGROUND AND OBJECTIVES: Platelets for transfusion have a shelf-life of 7 days, limiting availability and leading to wastage. Cryopreservation at -80°C extends shelf-life to at least 1 year, but safety and effectiveness are uncertain. MATERIALS AND METHODS: This single centre blinded pilot trial enrolled adult cardiac surgery patients who were at high risk of platelet transfusion. If treating clinicians determined platelet transfusion was required, up to three units of either cryopreserved or liquid-stored platelets intraoperatively or during intensive care unit admission were administered. The primary outcome was protocol safety and feasibility. RESULTS: Over 13 months, 89 patients were randomized, 23 (25.8%) of whom received a platelet transfusion. There were no differences in median blood loss up to 48 h between study groups, or in the quantities of study platelets or other blood components transfused. The median platelet concentration on the day after surgery was lower in the cryopreserved platelet group (122 × 103 /µl vs. 157 × 103 /µl, median difference 39.5 ×103 /µl, p = 0.03). There were no differences in any of the recorded safety outcomes, and no adverse events were reported on any patient. Multivariable adjustment for imbalances in baseline patient characteristics did not find study group to be a predictor of 24-h blood loss, red cell transfusion or a composite bleeding outcome. CONCLUSION: This pilot randomized controlled trial demonstrated the feasibility of the protocol and adds to accumulating data supporting the safety of this intervention. Given the clear advantage of prolonged shelf-life, particularly for regional hospitals in New Zealand, a definitive non-inferiority phase III trial is warranted.

Regulating the Tyrell Corporation: the Emergence of Novel Beings.

Emerging biotechnologies and advances in computer science promise the arrival of novel beings possessed of some degree of moral status, even potentially sentient or sapient life. Such a manifestation will constitute an epochal change, and perhaps threaten Homo sapiens' status as the only being generally considered worthy of personhood and its contingent protections; as well as being the root of any number of social and legal issues. The law as it stands is not likely to be capable of managing or adapting to this challenge. This paper highlights the likely societal ramifications of novel beings and the gaps in the legislation which is likely to be relied upon to respond to these. In so doing, the authors make a case for the development of new regulatory structures to manage the moral issues surrounding this new technological upheaval.

An international comparison of HIV prevalence and incidence in blood donors and general population: a BEST Collaborative study.

BACKGROUND AND OBJECTIVES: Efficiency in mitigating HIV transmission risk by transfusion may vary internationally. We compared HIV prevalence and incidence in blood donors across different jurisdictions in relation to those rates in the general population and differences in deferral practices. MATERIALS AND METHODS: Data from 2007 to 2016 were collected in Australia, Brazil (São Paulo), Canada, England, France, Italy, Ireland, Japan, the Netherlands, New Zealand, Norway, Spain (Basque Country), USA (Vitalant) and Wales. For each country/region, the number of HIV antibody-positive donations and nucleic acid testing (NAT)-only-positive donations was broken down according to first-time or repeat donor status, along with the relevant denominators. RESULTS: There is a modest correlation between HIV prevalence among first-time donors and HIV prevalence in the general population. However, rates of HIV-positive donations in repeat donors, a proxy for incidence, do not correlate with incidence rates in the general population. Rates in donors from Italy and Basque Country, where deferral criteria for men having sex with men are less stringent, are higher compared with most other jurisdictions. Rates of NAT-only-positive donations are extremely low and do not differ significantly after adjustment for multiple comparisons. CONCLUSION: Donor HIV rates are only weakly associated with those observed in the general population. Countries with less stringent deferral criteria have higher HIV rates in their donor population, but the rates remain very low.

Shifting food web structure during dam removal-Disturbance and recovery during a major restoration action.

We measured food availability and diet composition of juvenile salmonids over multiple years and seasons before and during the world's largest dam removal on the Elwha River, Washington State. We conducted these measurements over three sediment-impacted sections (the estuary and two sections of the river downstream of each dam) and compared these to data collected from mainstem tributaries not directly affected by the massive amount of sediment released from the reservoirs. We found that sediment impacts from dam removal significantly reduced invertebrate prey availability, but juvenile salmon adjusted their foraging so that the amount of energy in diets was similar before and during dam removal. This general pattern was seen in both river and estuary habitats, although the mechanisms driving the change and the response differed between habitats. In the estuary, the dietary shifts were related to changes in invertebrate assemblages following a hydrological transition from brackish to freshwater caused by sediment deposition at the river's mouth. The loss of brackish invertebrate species caused fish to increase piscivory and rely on new prey sources such as plankton. In the river, energy provided to fish by Ephemeroptera, Plecoptera, and Trichoptera taxa before dam removal was replaced first by terrestrial invertebrates, and then by sediment-tolerant taxa such as Chironomidae. The results of our study are consistent with many others that have shown sharp declines in invertebrate density during dam removal. Our study further shows how those changes can move through the food web and affect fish diet composition, selectivity, and energy availability. As we move further along the dam removal response trajectory, we hypothesize that food web complexity will continue to increase as annual sediment load now approaches natural background levels, anadromous fish have recolonized the majority of the watershed between and above the former dams, and revegetation and microhabitats continue to develop in the estuary.

Forty Years of Assessing Neurodevelopmental and Behavioral Effects of Prenatal Alcohol Exposure in Infants: What Have We Learned?

It has been known for over 4 decades that prenatal alcohol exposure (PAE) can adversely affect neurodevelopment and behavior (NDB). Yet, early detection of altered NDB due to PAE continues to present a major clinical challenge. Identification of altered NDB in the first 2 years of life, before higher-order cognitive processes develop, invites early interventions for affected children to improve long-term outcomes. Studies published in English from January of 1980 to July of 2018 were identified in PubMed/MEDLINE. The review focused on prospective birth cohort studies which used standardized NDB assessments in children up to 2 years of age, wherein PAE was the main exposure and NDB was the main outcome. NDB was categorized into the domains of neurocognitive, adaptive, and self-regulation based on the 2016 Updated Clinical Guidelines for Diagnosing fetal alcohol spectrum disorder. An initial search resulted in 1,867 articles for which we reviewed abstracts; 114 were selected for full-text review; and 3 additional abstracts were identified through review of references in eligible publications. Thirty-one publications met criteria and were included: of these, 24 reported neurocognitive outcomes, 24 reported adaptive behavior outcomes, and 12 reported outcomes in the domain of self-regulation. Although self-regulation was assessed in the fewest number of studies, 8/12 (75%) reported PAE-associated deficits. In contrast, results were mixed for the other 2 domains: 13/24 (54%) of the selected studies that included neurocognitive outcomes showed poorer performance following PAE, and 8/24 (33%) studies that assessed adaptive functioning found significant differences between PAE and comparison infants. There is considerable evidence to support the value of early-life assessments of infant NDB when PAE is known or suspected. More studies focusing on infant self-regulation, in particular, are needed to determine the utility of early evaluation of this critical developmental domain in infants with PAE.

Conceptualizing Ecological Responses to Dam Removal: If You Remove It, What's to Come?

One of the desired outcomes of dam decommissioning and removal is the recovery of aquatic and riparian ecosystems. To investigate this common objective, we synthesized information from empirical studies and ecological theory into conceptual models that depict key physical and biological links driving ecological responses to removing dams. We define models for three distinct spatial domains: upstream of the former reservoir, within the reservoir, and downstream of the removed dam. Emerging from these models are response trajectories that clarify potential pathways of ecological transitions in each domain. We illustrate that the responses are controlled by multiple causal pathways and feedback loops among physical and biological components of the ecosystem, creating recovery trajectories that are dynamic and nonlinear. In most cases, short-term effects are typically followed by longer-term responses that bring ecosystems to new and frequently predictable ecological condition, which may or may not be similar to what existed prior to impoundment.

Improving Long-Term Care Facility Disaster Preparedness and Response: A Literature Review.

Long-term care facilities (LTCFs) and their residents are especially susceptible to disruptions associated with natural disasters and often have limited experience and resources for disaster planning and response. Previous reports have offered disaster planning and response recommendations. We could not find a comprehensive review of studied interventions or facility attributes that affect disaster outcomes in LTCFs and their residents. We reviewed articles published from 1974 through September 30, 2015, that studied disaster characteristics, facility characteristics, patient characteristics, or an intervention that affected outcomes for LTCFs experiencing or preparing for a disaster. Twenty-one articles were included in the review. All of the articles fell into 1 of the following categories: facility or disaster characteristics that predicted preparedness or response, interventions to improve preparedness, and health effects of disaster response, most often related to facility evacuation. All of the articles described observational studies that were heterogeneous in design and metrics. We believe that the evidence-based literature supports 6 specific recommendations for facilities, governmental agencies, health care communities and academia. These include integrated and coordinated disaster planning, staff training, careful consideration before governments order mandatory evacuations, anticipation of the increased medical needs of LTCF residents following a disaster, and the need for more outcomes research. (Disaster Med Public Health Preparedness. 2017;11:140-149).

Palliative Care for American Indians and Alaska Natives: A Review of the Literature.

BACKGROUND: Little is known about optimal palliative and end-of-life care for American Indians and Alaska Natives (AIs/ANs). METHODS: We searched MEDLINE, the Cochrane library, EBSCOhost, (PsycINFO, CINAHL Complete), and the University of New Mexico (UNM) Health Sciences Library and Informatics Center Native Health Database for search terms related to palliative care and AIs/ANs as of December 1, 2015. We included English language, peer-reviewed articles describing palliative care projects, programs, or studies in AI/AN populations or communities. We excluded case series, opinion or reflection pieces, and dissertations and articles addressing Pacific Islanders. RESULTS: Our search strategy yielded 294 references, of which we included 10 publications. Study methods and outcome measures were heterogeneous, and many studies were small and/or subject to multiple biases. Common themes included the importance of culturally appropriate communication, multiple barriers to treatment, and less frequent use of advance directives than other populations. CONCLUSIONS: Heterogeneity of study types, population, and small sample sizes makes it hard to draw broad conclusions regarding the best way to care for AIs/ANs. More studies are needed to assess this important topic.

Relapsing Acute Axonal Neuropathy in Hereditary Fructose Intolerance.

BACKGROUND: A severe neurological abnormality has not been previously described in individuals with hereditary fructose intolerance, which typically presents early in childhood with severe metabolic acidosis and hypoglycemia. PATIENT DESCRIPTION: We describe a boy who by age five years had required multiple admissions to the pediatric intensive care unit for an aggressive and atypical, relapsing and remitting neuropathy with features of acute motor axonal neuropathy (AMAN). It was later discovered that he also had undiagnosed hereditary fructose intolerance, and the severity and frequency of his neurological episodes diminished following an exclusion diet. His asymptomatic younger brother was diagnosed with hereditary fructose intolerance on screening. He is on a fructose-free diet and has not developed neurological symptoms. CONCLUSIONS: Ongoing low-level exposure to fructose prior to diagnosis may have contributed to our patient's neurological dysfunction. Early diagnosis and treatment may prevent neurological complications of hereditary fructose intolerance.

Non-invasive ventilation in paediatric critical care.

Non-invasive ventilation (NIV) is a well recognised and increasingly prevalent intervention in the paediatric critical care setting. In the acute setting NIV is used to provide respiratory support in a flexible manner that avoids a requirement for endotracheal intubation or tracheostomy, with the aim of avoiding the complications of invasive ventilation. This article will explore the physiological benefits, complications and epidemiology of the different modes of NIV including continuous positive airway pressure (CPAP), non-invasive positive pressure ventilation (NIPPV) and high-flow nasal cannula oxygen (HFNC). The currently available equipment and patient interfaces will be described, and the practical aspects of using NIV clinically will be explored. The current evidence for use of NIV in different clinical settings will be discussed, drawing on adult and neonatal as well as paediatric literature.

Expression of a single-chain human leukocyte antigen-DRA/DRB3*01:01 molecule and differential binding of a monoclonal antibody in the presence of specifically bound human platelet antigen-1a peptide.

BACKGROUND: Studies show that 1 in 1200 neonates have a low platelet (PLT) count due to alloimmunization against human PLT antigen (HPA)-1a (ß3 -L33). This mainly occurs in HPA-1a-negative mothers who are positive for the human leukocyte antigen (HLA)-DRB3*01:01 allele, but only about one-third of cases will mount an effective alloimmune response. The development of specific treatment modalities requires that the mechanisms driving the maternal alloimmune response against the fetal PLTs be further explored. An antibody reagent that has a different binding affinity to HLA-DRA/DRB3*01:01 with and without the ß3 -L33 peptide would be a valuable reagent to study peptide presentation on maternal antigen-presenting cells. STUDY DESIGN AND METHODS: To identify such antibodies, HLA-DRA/DRB3*01:01 was recombinantly expressed in Drosophila S2 cells. To delineate the epitope of interesting antibodies, seven mutant HLA-DRA/DRB3*01:01 molecules were generated by site-directed mutagenesis introducing naturally occurring amino acid changes encoded by DRB3*02 and DRB3*03 alleles. RESULTS: The murine monoclonal antibody (MoAb) DA2 showed robust binding by enzyme-linked immunosorbent assay to recombinant HLA-DRA/DRB3*01:01, but binding was reduced in the presence of ß3 -L33 peptide. The binding affinity of DA2 to the mutant HLA-DRA/DRB3*0101 in which serine at Position 60 of the ß1-chain was replaced by tyrosine was greatly enhanced. Interestingly the binding of DA2 to the mutant was not reduced by the presence of ß3 -L33 peptide. CONCLUSION: The results of this study generate a molecular model of the interaction of the HLA-DRA/DRB3*01:01 molecule with MoAb DA2. This will inform functional studies with the recombinant Class II molecules.