Nanomaterials continue to bring promising advances to science and technology. In concert have come calls for increased regulatory oversight to ensure their appropriate identification and evaluation, ...which has led to extensive discussions about nanomaterial definitions. Numerous nanomaterial definitions have been proposed by government, industry, and standards organizations. We conducted a comprehensive comparative assessment of existing nanomaterial definitions put forward by governments to highlight their similarities and differences. We found that the size limits used in different definitions were inconsistent, as were considerations of other elements, including agglomerates and aggregates, distributional thresholds, novel properties, and solubility. Other important differences included consideration of number size distributions versus weight distributions and natural versus intentionally-manufactured materials. Overall, the definitions we compared were not in alignment, which may lead to inconsistent identification and evaluation of nanomaterials and could have adverse impacts on commerce and public perceptions of nanotechnology. We recommend a set of considerations that future discussions of nanomaterial definitions should consider for describing materials and assessing their potential for health and environmental impacts using risk-based approaches within existing assessment frameworks. Our intent is to initiate a dialogue aimed at achieving greater clarity in identifying those nanomaterials that may require additional evaluation, not to propose a formal definition.
•Regulatory bodies have developed different definitions of “nanomaterial”.•The scope of and concepts within definitions (e.g., size) are often inconsistent.•Inconsistencies in definitions exist among and within governments.•A substance may be a nanomaterial under one regulatory scheme, but not another.•Key considerations for safety assessment are absent from several definitions.
Stable flies, Stomoxys calcitrans (L.), are among the most damaging arthropod pests of cattle worldwide. The last estimate of their economic impact on United States cattle production was published 20 ...yr ago and placed losses at $608 million. Subsequently, several studies of effects of stable flies on beef cattle weight gain and feed efficiency have been published, and stable flies have become increasingly recognized as pests of cattle on pasture and range. We analyzed published studies and developed yield-loss functions to relate stable fly infestation levels to cattle productivity, and then estimated the economic impact of stable flies on cattle production in the United States. Four industry sectors were considered: dairy, cow-calf, pastured stockers, and feeder cattle. In studies reporting stable fly infestation levels of individual herds, median annual per animal production losses were estimated to be 139 kg of milk for dairy cows, and 6, 26, and 9 kg body weight for preweanling calves, pastured stockers, and feeder cattle, respectively. The 200,000 stable flies emerging from an average sized winter hay feeding site reduce annual milk production of 50 dairy cows by an estimated 890 kg and weight gain of 50 preweanling calves, stockers, or feeder cattle by 58, 680, or 84 kg. In 2009 dollars, the value of these losses would be $254, $132, $1,279, or $154, respectively. Using cattle inventories and average prices for 2005–2009, and median monthly infestation levels, national losses are estimated to be $360 million for dairy cattle, $358 million for cow-calf herds, $1,268 million for pastured cattle, and $226 million for cattle on feed, for a total impact to U.S. cattle industries of $2,211 million per year. Excluded from these estimates are effects of stable flies on feed conversion efficiency, animal breeding success, and effects of infested cattle on pasture and water quality. Additional research on the effects of stable flies on high-production dairy cows and nursing beef calves is needed to increase the reliability of the estimates.
Transfusion-associated circulatory overload (TACO) is a leading cause of transfusion-related fatalities, but its incidence and associated patient and transfusion characteristics are poorly ...understood. To inform surgical transfusion practice and to begin mitigating perioperative TACO, the authors aimed to define its epidemiology.
In this retrospective cohort study, the medical records of adult patients undergoing noncardiac surgery with general anesthesia during 2004 or 2011 and receiving intraoperative transfusions were screened using an electronic algorithm for identification of TACO. Those patients who were screened as high probability for TACO underwent rigorous manual review. Univariate and multivariate analyses evaluated associations between patient and transfusion characteristics with TACO rates in a before-and-after study design.
A total of 2,162 and 1,908 patients met study criteria for 2004 and 2011, respectively. The incidence of TACO was 5.5% (119 of 2,162) in 2004 versus 3.0% (57 of 1,908) in 2011 (P < 0.001), with comparable rates for men (4.8% 98 of 2,023) and women (3.8% 78 of 2,047) (P = 0.09). Overall, vascular (12.1% 60 of 497), transplant (8.8% 17 of 193), and thoracic surgeries (7.2% 10 of 138) carried the highest TACO rates. Obstetric and gynecologic patients had the lowest rate (1.4% 4 of 295). The incidence of TACO increased with volume transfused, advancing age, and total intraoperative fluid balance (all P < 0.001).
The incidence of perioperative TACO is similar to previous estimates in nonsurgical populations. There was a reduction in TACO rate between 2004 and 2011, with incidence patterns remaining comparable in subgroup analyses. Future efforts exploring risk factors for TACO may guide preventive or therapeutic interventions, helping to further mitigate this transfusion complication.
The accuracy of absorbed dose calculations in personalized internal radionuclide therapy is directly related to the accuracy of the activity (or activity concentration) estimates obtained at each of ...the imaging time points. MIRD Pamphlet no. 23 presented a general overview of methods that are required for quantitative SPECT imaging. The present document is next in a series of isotope-specific guidelines and recommendations that follow the general information that was provided in MIRD 23. This paper focuses on (177)Lu (lutetium) and its application in radiopharmaceutical therapy.
Medical and healthcare practice is likely to see fundamental changes in the future that will require a different approach to the way in which we educate, train, and assess the next generation of ...healthcare professionals. The anatomical sciences will need to be part of that challenge so they continue to play a full role in preparing students with the knowledge and ever increasingly the skills and competencies that will contribute to the fundamentals of their future capacity to practice effectively. Although there have been significant advances in anatomical science pedagogy, by reviewing learning and assessment in an apparently unrelated field, provides an opportunity to bring a different perspective and enable appropriate challenge of the current approaches in anatomy. Design learning has had to continually reimagine itself in response to the shifting landscape in design practice and the threats associated with technology and societal change. Design learning has also long used a student-centric active pedagogy and allied authentic assessment methods and, therefore, provides an ideal case study to help inform future changes required in anatomical learning and assessment.
IMPORTANCE: Post–cardiopulmonary bypass (CPB) coagulopathy and bleeding are among the most common reasons for blood product transfusion in surgical practices. Current retrospective data suggest lower ...transfusion rates and blood loss in patients receiving prothrombin complex concentrate (PCC) compared with plasma after cardiac surgery. OBJECTIVE: To analyze perioperative bleeding and transfusion outcomes in patients undergoing cardiac surgery who develop microvascular bleeding and receive treatment with either PCC or plasma. DESIGN, SETTING, AND PARTICIPANTS: A single-institution, prospective, randomized clinical trial performed at a high-volume cardiac surgical center. Patients were aged 18 years or older and undergoing cardiac surgery with CPB. Patients undergoing complex cardiac surgical procedures (eg, aortic replacement surgery, multiple procedures, or repeated sternotomy) were preferentially targeted for enrollment. During the study period, 756 patients were approached for enrollment, and 553 patients were randomized. Of the 553 randomized patients, 100 patients met criteria for study intervention. INTERVENTIONS: Patients with excessive microvascular bleeding, a prothombin time (PT) greater than 16.6 seconds, and an international normalized ratio (INR) greater than 1.6 were randomized to receive treatment with either PCC or plasma. The PCC dose was 15 IU/kg or closest standardized dose; the plasma dose was a suggested volume of 10 to 15 mL/kg rounded to the nearest unit. MAIN OUTCOMES AND MEASURES: The primary outcome was postoperative bleeding (chest tube output) from the initial postsurgical intensive care unit admission through midnight on postoperative day 1. Secondary outcomes were PT/INR, rates of intraoperative red blood cell (RBC) transfusion after treatment, avoidance of allogeneic transfusion from the intraoperative period to the end of postoperative day 1, postoperative bleeding, and adverse events. RESULTS: One hundred patients (mean SD age, 66.8 13.7 years; 61 61.0% male; and 1 1.0% Black, 1 1.0% Hispanic, and 98 98.0% White) received the study intervention (49 plasma and 51 PCC). There was no significant difference in chest tube output between the plasma and PCC groups (median IQR, 1022 799-1575 mL vs 937 708-1443 mL). After treatment, patients in the PCC arm had a greater improvement in PT (effect estimate, −1.37 seconds 95% CI, −1.91 to −0.84; P < .001) and INR (effect estimate, −0.12 95% CI, −0.16 to −0.07; P < .001). Fewer patients in the PCC group required intraoperative RBC transfusion after treatment (7 of 51 patients 13.7% vs 15 of 49 patients 30.6%; P = .04); total intraoperative transfusion rates were not significantly different between groups. Seven (13.7%) of 51 patients receiving PCCs avoided allogeneic transfusion from the intraoperative period to the end of postoperative day 1 vs none of those receiving plasma. There were no significant differences in postoperative bleeding, transfusions, or adverse events. CONCLUSIONS AND RELEVANCE: The results of this study suggest a similar overall safety and efficacy profile for PCCs compared with plasma in this clinical context, with fewer posttreatment intraoperative RBC transfusions, improved PT/INR correction, and higher likelihood of allogeneic transfusion avoidance in patients receiving PCCs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02557672
The American Society of Anesthesiologists (ASA) Annual Meeting is the primary venue for anesthesiologists to present research, share innovations, and build networks. Herein, we describe gender ...representation for physician speakers at the Annual Meeting relative to the specialty overall. Details of ASA Annual Meeting presentations for individuals and panels were abstracted from the ASA archives for 2011–2016. Observed speaker gender composition was compared to expected composition based on the gender distribution of members of the ASA. There were 5167 speaker slots across 2025 presentations and panels. Of the speaker slots, 3874 were assigned to men and 1293 to women. Speaker slot gender composition was relatively consistent between 2011 and 2016 (annual percentage 22.3%–27.7% women, trend test P = .062). ASA membership composition of women increased slightly over the study period (24%–28%). The overall observed number of women in speaker slots over the study period did not differ significantly from what would be expected based on the ASA membership composition (25.0% observed versus 25.9% expected; P = .153). However, the percentage of single speakers who were women was significantly less than would be expected based on the ASA gender distribution (20.2% observed versus 25.9% expected; P < .001). Interestingly, for panels that included 2–5 anesthesiologists, single-gender panels were more common than would be expected by chance, with all-male panels predominating (all P < .01). The gender composition of speakers at the ASA Annual Meeting largely reflected gender composition within the specialty, although women were not overrepresented at any meeting. The predominance of single-gender panels and underrepresentation of women as single speakers is a potential target to improve gender representation.
Highlights • A recombinant HVT vaccine expressing a H5 HA gene provided homologous and heterologous protection. • Antibodies exhibited high levels of reaction against homologous but not heterologous ...H5 virus. • Lymphocytes from vaccinated chickens recognized target cells infected with H5, H6, H7, or H9 AI. • Live recombinant vaccines induce humoral and cellular immunity which contribute to protection.
Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and ...lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice.
Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma) or Granta (mantle cell lymphoma) xenografts, utilizing an anti-CD20 antibody-streptavidin conjugate (1F5-SA) and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin second step reagent.
The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq) as for 177Lu (0.6 Gy/MBq). More importantly, therapy with 90Y-DOTA-biotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0% cured with 177Lu-PRIT. Toxicities were comparable with both isotopes.
90Y was therapeutically superior to 177Lu for streptavidin-biotin PRIT approaches in these human lymphoma xenograft models.
BACKGROUND:Multimodal analgesia is standard practice for total knee arthroplasty; however, the role of regional techniques in improved perioperative outcomes remains unknown. The authors hypothesized ...that peripheral nerve blockade would result in lower pain scores and opioid consumption than two competing periarticular injection solutions.
METHODS:This three-arm, nonblinded trial randomized 165 adults undergoing unilateral primary total knee arthroplasty to receive (1) femoral catheter plus sciatic nerve blocks, (2) ropivacaine-based periarticular injection, or (3) liposomal bupivacaine-based periarticular injection. Primary outcome was maximal pain during postoperative day 1 (0 to 10, numerical pain rating scale) in intention-to-treat analysis. Additional outcomes included pain scores and opioid consumption for postoperative days 0 to 2 and 3 months.
RESULTS:One hundred fifty-seven study patients received peripheral nerve block (n = 50), ropivacaine (n = 55), or liposomal bupivacaine (n = 52) and reported median maximal pain scores on postoperative day 1 of 3, 4, and 4.5 and on postoperative day 0 of 1, 4, and 5, respectively (average pain scores for postoperative day 00.6, 1.7, and 2.4 and postoperative day 12.5, 3.5, and 3.7). Postoperative day 1 median maximal pain scores were significantly lower for peripheral nerve blockade compared to liposomal bupivacaine-based periarticular injection (P = 0.016; Hodges–Lehmann median difference 95% CI = −1 −2 to 0). After postanesthesia care unit discharge, postoperative day 0 median maximal and average pain scores were significantly lower for peripheral nerve block compared to both periarticular injections (ropivacainemaximal −2 −3 to −1; P < 0.001; average −0.8 −1.3 to −0.2; P = 0.003; and liposomal bupivacainemaximal −3 −4 to −2; P < 0.001; average −1.4 −2.0 to −0.8; P < 0.001).
CONCLUSIONS:Ropivacaine-based periarticular injections provide pain control comparable on postoperative days 1 and 2 to a femoral catheter and single-injection sciatic nerve block. This study did not demonstrate an advantage of liposomal bupivacaine over ropivacaine in periarticular injections for total knee arthroplasty.
PDF
