Room‐temperature liquid metals, such as nontoxic gallium alloys, show enormous promise to revolutionize stretchable electronics for next‐generation soft robotic, e‐skin, and wearable technologies. ...Core–shell particles of liquid metal with surface‐bound acrylate ligands are synthesized and polymerized together to create cross‐linked particle networks comprising >99.9% liquid metal by weight. When stretched, particles within these polymerized liquid metal networks (Poly‐LMNs) rupture and release their liquid metal payload, resulting in a rapid 108‐fold increase in the network's conductivity. These networks autonomously form hierarchical structures that mitigate the deleterious effects of strain on electronic performance and give rise to emergent properties. Notable characteristics include nearly constant resistances over large strains, electronic strain memory, and increasing volumetric conductivity with strain to over 20 000 S cm−1 at >700% elongation. Furthermore, these Poly‐LMNs exhibit exceptional performance as stretchable heaters, retaining 96% of their areal power across relevant physiological strains. Remarkable electromechanical properties, responsive behaviors, and facile processing make Poly‐LMNs ideal for stretchable power delivery, sensing, and circuitry.
Core–shell liquid metal particles functionalized with acrylate ligands are polymerized to create cross‐linked particle networks. When these polymerized liquid metal networks are stretched, their constituent particles rupture and the network transitions from insulating to conductive. These networks autonomously form hierarchical structures that help maintain stable electrical behavior under high strains and exhibit excellent performance as stretchable conductors and heaters.
There is considerable uncertainty regarding the optimal haemoglobin threshold for the use of red blood cell (RBC) transfusions in anaemic patients. Blood is a scarce resource, and in some countries, ...transfusions are less safe than others because of a lack of testing for viral pathogens. Therefore, reducing the number and volume of transfusions would benefit patients.
The aim of this review was to compare 30-day mortality and other clinical outcomes in participants randomized to restrictive versus liberal red blood cell (RBC) transfusion thresholds (triggers) for all conditions. The restrictive transfusion threshold uses a lower haemoglobin level to trigger transfusion (most commonly 7 g/dL or 8 g/dL), and the liberal transfusion threshold uses a higher haemoglobin level to trigger transfusion (most commonly 9 g/dL to 10 g/dL).
We identified trials by searching CENTRAL (2016, Issue 4), MEDLINE (1946 to May 2016), Embase (1974 to May 2016), the Transfusion Evidence Library (1950 to May 2016), the Web of Science Conference Proceedings Citation Index (1990 to May 2016), and ongoing trial registries (27 May 2016). We also checked reference lists of other published reviews and relevant papers to identify any additional trials.
We included randomized trials where intervention groups were assigned on the basis of a clear transfusion 'trigger', described as a haemoglobin (Hb) or haematocrit (Hct) level below which a red blood cell (RBC) transfusion was to be administered.
We pooled risk ratios of clinical outcomes across trials using a random-effects model. Two people extracted the data and assessed the risk of bias. We conducted predefined analyses by clinical subgroups. We defined participants randomly allocated to the lower transfusion threshold as 'restrictive transfusion' and to the higher transfusion threshold as 'liberal transfusion'.
A total of 31 trials, involving 12,587 participants, across a range of clinical specialities (e.g. surgery, critical care) met the eligibility criteria. The trial interventions were split fairly equally with regard to the haemoglobin concentration used to define the restrictive transfusion group. About half of them used a 7 g/dL threshold, and the other half used a restrictive transfusion threshold of 8 g/dL to 9 g/dL. The trials were generally at low risk of bias .Some items of methodological quality were unclear, including definitions and blinding for secondary outcomes.Restrictive transfusion strategies reduced the risk of receiving a RBC transfusion by 43% across a broad range of clinical specialties (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.49 to 0.65; 12,587 participants, 31 trials; high-quality evidence), with a large amount of heterogeneity between trials (I² = 97%). Overall, restrictive transfusion strategies did not increase or decrease the risk of 30-day mortality compared with liberal transfusion strategies (RR 0.97, 95% CI 0.81 to 1.16, I² = 37%; N = 10,537; 23 trials; moderate-quality evidence) or any of the other outcomes assessed (i.e. cardiac events (low-quality evidence), myocardial infarction, stroke, thromboembolism (high-quality evidence)). Liberal transfusion did not affect the risk of infection (pneumonia, wound, or bacteraemia).
Transfusing at a restrictive haemoglobin concentration of between 7 g/dL to 8 g/dL decreased the proportion of participants exposed to RBC transfusion by 43% across a broad range of clinical specialities. There was no evidence that a restrictive transfusion strategy impacts 30-day mortality or morbidity (i.e. mortality at other points, cardiac events, myocardial infarction, stroke, pneumonia, thromboembolism, infection) compared with a liberal transfusion strategy. There were insufficient data to inform the safety of transfusion policies in certain clinical subgroups, including acute coronary syndrome, myocardial infarction, neurological injury/traumatic brain injury, acute neurological disorders, stroke, thrombocytopenia, cancer, haematological malignancies, and bone marrow failure. The findings provide good evidence that transfusions with allogeneic RBCs can be avoided in most patients with haemoglobin thresholds above 7 g/dL to 8 g/dL.
The relationship between gastrointestinal (GI) bacteria and the response to anti-CTLA-4 and anti-PD-1 immunotherapy in the treatment of cancer can potentially be enhanced to allow patients to ...maximally respond to these treatments. Insight into the complex interaction between gut microbiota and the human adaptive immune system will help guide future immunotherapeutic cancer treatments to allow a more robust clinical response and fewer adverse effects in patients requiring these drugs. This review highlights these interactions as well as the potential for the creation of "oncomicrobiotics" that would selectively tailor one's GI bacteria to maximally respond to anti-CTLA-4 and anti-PD-1 treatments will fewer adverse effects.
CTLA-4 is an antigen on the surface of T cells which, upon stimulation, leads to inhibition of activated T cells to terminate the immune response. However, many types of tumor cells can upregulate CTLA-4 in the tumor microenvironment, allowing these cells to evade targeting and destruction by the body's immune system by prematurely inhibiting T cells. Increased representation of
,
and the
in the GI tract of patients receiving CTLA-4-based immunotherapy led to a stronger therapeutic effect while minimizing adverse side effects such as colitis. In addition, by introducing bacteria involved in vitamin B and polyamine transport to the GI tracts of patients treated with anti-CTLA-4 drugs led to increased resistance to colitis while maintaining therapeutic efficacy. PD-1 is another molecule upregulated in many tumor microenvironments which acts in a similar manner to CTLA-4 to tone down the anti-neoplastic actions of T cells. Antibodies to PD-1 have shown promise to help allow the body's natural immune response to appropriately target and destroy tumor cells. The presence of
and
,
and
in the GI tracts of cancer patients has the potential to create a more robust immune response to anti-PD-1 drugs and prolonged survival. The development of "oncomicrobiotics" has the potential to help tailor one's gut microbiota to allow patients to maximally respond to immunotherapy without sacrificing increases in toxicity. These oncomicrobiotics may possibly include antibiotics, probiotics, postbiotics and/or prebiotics. However, many challenges lie ahead in the creation of oncomicrobiotics.
The creation of oncomicrobiotics may allow many patients receiving anti-CTLA-4 and PD-1 immunotherapy to experience prolonged survival and a better quality of life.
Although approximately 85 million units of red blood cells (RBCs) are transfused annually worldwide, transfusion practices vary widely. The AABB (formerly, the American Association of Blood Banks) ...developed this guideline to provide clinical recommendations about hemoglobin concentration thresholds and other clinical variables that trigger RBC transfusions in hemodynamically stable adults and children.
These guidelines are based on a systematic review of randomized clinical trials evaluating transfusion thresholds. We performed a literature search from 1950 to February 2011 with no language restrictions. We examined the proportion of patients who received any RBC transfusion and the number of RBC units transfused to describe the effect of restrictive transfusion strategies on RBC use. To determine the clinical consequences of restrictive transfusion strategies, we examined overall mortality, nonfatal myocardial infarction, cardiac events, pulmonary edema, stroke, thromboembolism, renal failure, infection, hemorrhage, mental confusion, functional recovery, and length of hospital stay. RECOMMENDATION 1: The AABB recommends adhering to a restrictive transfusion strategy (7 to 8 g/dL) in hospitalized, stable patients (Grade: strong recommendation; high-quality evidence). RECOMMENDATION 2: The AABB suggests adhering to a restrictive strategy in hospitalized patients with preexisting cardiovascular disease and considering transfusion for patients with symptoms or a hemoglobin level of 8 g/dL or less (Grade: weak recommendation; moderate-quality evidence). RECOMMENDATION 3: The AABB cannot recommend for or against a liberal or restrictive transfusion threshold for hospitalized, hemodynamically stable patients with the acute coronary syndrome (Grade: uncertain recommendation; very low-quality evidence). RECOMMENDATION 4: The AABB suggests that transfusion decisions be influenced by symptoms as well as hemoglobin concentration (Grade: weak recommendation; low-quality evidence).
The hemoglobin threshold at which postoperative red-cell transfusion is warranted is controversial. We conducted a randomized trial to determine whether a higher threshold for blood transfusion would ...improve recovery in patients who had undergone surgery for hip fracture.
We enrolled 2016 patients who were 50 years of age or older, who had either a history of or risk factors for cardiovascular disease, and whose hemoglobin level was below 10 g per deciliter after hip-fracture surgery. We randomly assigned patients to a liberal transfusion strategy (a hemoglobin threshold of 10 g per deciliter) or a restrictive transfusion strategy (symptoms of anemia or at physician discretion for a hemoglobin level of <8 g per deciliter). The primary outcome was death or an inability to walk across a room without human assistance on 60-day follow-up.
A median of 2 units of red cells were transfused in the liberal-strategy group and none in the restrictive-strategy group. The rates of the primary outcome were 35.2% in the liberal-strategy group and 34.7% in the restrictive-strategy group (odds ratio in the liberal-strategy group, 1.01; 95% confidence interval CI, 0.84 to 1.22), for an absolute risk difference of 0.5 percentage points (95% CI, -3.7 to 4.7). The rates of in-hospital acute coronary syndrome or death were 4.3% and 5.2%, respectively (absolute risk difference, -0.9%; 99% CI, -3.3 to 1.6), and rates of death on 60-day follow-up were 7.6% and 6.6%, respectively (absolute risk difference, 1.0%; 99% CI, -1.9 to 4.0). The rates of other complications were similar in the two groups.
A liberal transfusion strategy, as compared with a restrictive strategy, did not reduce rates of death or inability to walk independently on 60-day follow-up or reduce in-hospital morbidity in elderly patients at high cardiovascular risk. (Funded by the National Heart, Lung, and Blood Institute; FOCUS ClinicalTrials.gov number, NCT00071032.).
Global surface pressure measurements have been carried out on a 7° half-angle circular cone/flare model at nominally zero angle of attack using pressure-sensitive paint (PSP). These experiments were ...conducted to illustrate the PSP technique’s usefulness and effectiveness at measuring the unsteady structures inherent to hypersonic shock-wave/boundary-layer interactions (SWBLI) on a global scale. Mean and fluctuating surface pressure was measured with a temperature-corrected, high-frequency-response (
≈
10
kHz) anodized-aluminum pressure-sensitive paint (AA-PSP). This AA-PSP was made in-house to provide the high frequency response required. Methodologies for tracking the boundary-layer separation and reattachment shock feet in both time-averaged and instantaneous senses are provided and discussed. Excellent agreement is observed between the different metrics. In addition, spectral analyses were conducted on a global scale providing insights into the unsteady dynamics of the shock feet and structures under the separated shear layer. These spectral analyses identified a smooth, low-frequency bandwidth centered at
≈
500
Hz, which is characteristic of the shock-foot oscillations. These experimental findings validate the usefulness of AA-PSP to provide global physical insights of unsteady SWBLI surface behavior in the hypersonic flow regime. Similar methodologies can be incorporated in future experiments to investigate complex and novel SWBLI.
Graphic abstract
Genetics and the microbiota Although it is well known that race and ethnicity are poor proxies for genetic ancestry, these factors may be somewhat correlated. ...host genetics may marginally ...contribute to racial/ethnic differences in gastrointestinal microbial composition and functionality. Periodontal disease may be attributable to complex and difficult-to-measure differences in socioeconomic and other social factors occurring over the life course that contribute to a lack of health care access and utilization. ...oral health metrics and their associated oral microbiota may be proxies for these complex exposures. ...the annual National Health and Nutrition Examination Survey (NHANES) ascertains the health and nutritional status of children and adults via questionnaires and biospecimen collection in a nationally representative sample of approximately 5000 individuals 13. Because of their oversampling of targeted groups of individuals, NHANES has become an invaluable resource for reliably estimating various US exposures, including those pertaining to social determinants of health. ...study populations like those represented in NHANES are particularly suitable for future collection of oral and fecal samples to characterize the gastrointestinal microbiota of a representative portion of the US population.
A measurement technique for identifying lee-side crossflow-induced boundary-layer separation on a blunt
7
∘
half-angle circular cone at high angle of attack has been developed and tested. Previous ...work has shown that local minima in root-mean-squared (rms) pressure fluctuations on the surface are good identifiers of separation. These surface pressure fluctuations are measured with a temperature-corrected, high-frequency-response anodized-aluminum pressure-sensitive paint (AA-PSP). This AA-PSP was made in-house to provide the high frequency response required for this work. The sensor’s frequency response of 3 kHz proved to be fast enough to detect lines of local minimum rms pressure fluctuations indicative of separation on the lee side of the cone for angles of attack from
9
.
8
∘
to
15
.
8
∘
. A shift in the separation location towards the windward side of the model was observed as angle of attack increased; however, the separation location converged to a constant azimuth for angles of attack greater than or equal to
1.8
×
the cone’s half angle.
Healthcare workers (HCW) are presumed to be at increased risk of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection due to occupational exposure to infected patients. However, ...there has been little epidemiological research to assess these risks.
We conducted a prospective cohort study of HCW (n = 546) and non-healthcare workers (NHCW; n = 283) with no known prior SARS-CoV-2 infection who were recruited from a large U.S. university and two affiliated university hospitals. In this cross-sectional analysis of data collected at baseline, we examined SARS-CoV-2 infection status (as determined by presence of SARS-CoV-2 RNA in oropharyngeal swabs) by healthcare worker status and role.
At baseline, 41 (5.0%) of the participants tested positive for SARS-CoV-2 infection, of whom 14 (34.2%) reported symptoms. The prevalence of SARS-CoV-2 infection was higher among HCW (7.3%) than in NHCW (0.4%), representing a 7.0% greater absolute risk (95% confidence interval for risk difference 4.7, 9.3%). The majority of infected HCW (62.5%) were nurses. Positive tests increased across the two weeks of cohort recruitment in line with rising confirmed cases in the hospitals and surrounding counties.
Overall, our results demonstrate that HCW had a higher prevalence of SARS-CoV-2 infection than NHCW. Continued follow-up of this cohort will enable us to monitor infection rates and examine risk factors for transmission.