Efficacy and feasibility of the RADA16 self-assembling peptide, PuraStat® for haemostasis in laparoscopic gynaecological surgery: A pilot study.

Bleeding after laparoscopic gynaecological surgery remains a potential complication. We assessed RADA16 (PuraStat®), a topical self-assembling peptide haemostatic agent, in a pilot study of 46 women undergoing laparoscopic gynaecological surgery. The primary outcome was intraoperative haemostatic efficacy for resection site bleeding. Haemostasis was achieved in all intraoperative bleeding situations (40/40 participants: 100%) with no clinically significant surgical bed bleeding or complications. Mean volume and time required to achieve haemostasis were 6 mL and 14 sec, respectively. This study suggests that PuraStat® is a safe, effective haemostatic agent in laparoscopic gynaecological surgery. Randomised controlled trials are warranted to confirm these findings.

Experience with dasatinib and nilotinib use in pregnancy.

Pregnancy in a patient with chronic myeloid leukemia presents a therapeutic challenge. Both dasatinib and nilotinib are indicated for first-line treatment as well as for treatment-resistant chronic myeloid leukemia. Animal studies with dasatinib or nilotinib demonstrate fetal skeletal malformations as well as significant mortality during organogenesis. The goal of this article is to review the experience to date of dasatinib and nilotinib in human pregnancy, specifically dasatinib and nilotinib dose, length of exposure, trimester of use, as well as patient and fetal outcomes. Based on the limited data, both dasatinib and nilotinib may cause fetal harm. Additionally, thorough analysis of the available literature indicates no correlation between dasatinib nor nilotinib dose, length of exposure, trimester of use, and deleterious patient or fetal outcomes can be concluded. Therefore, health care professionals need to regularly counsel women of child bearing potential with chronic myeloid leukemia regarding the risks of taking dasatinib or nilotinib during pregnancy. The safest potential therapeutic options for the management of chronic myeloid leukemia in pregnancy include temporary discontinuation of the tyrosine kinase inhibitor followed by observation or intervention with interferon alfa and/or leukapheresis.

Integrated Stochastic Model of DNA Damage Repair by Non-homologous End Joining and p53/p21-Mediated Early Senescence Signalling.

Unrepaired or inaccurately repaired DNA damage can lead to a range of cell fates, such as apoptosis, cellular senescence or cancer, depending on the efficiency and accuracy of DNA damage repair and on the downstream DNA damage signalling. DNA damage repair and signalling have been studied and modelled in detail separately, but it is not yet clear how they integrate with one another to control cell fate. In this study, we have created an integrated stochastic model of DNA damage repair by non-homologous end joining and of gamma irradiation-induced cellular senescence in human cells that are not apoptosis-prone. The integrated model successfully explains the changes that occur in the dynamics of DNA damage repair after irradiation. Simulations of p53/p21 dynamics after irradiation agree well with previously published experimental studies, further validating the model. Additionally, the model predicts, and we offer some experimental support, that low-dose fractionated irradiation of cells leads to temporal patterns in p53/p21 that lead to significant cellular senescence. The integrated model is valuable for studying the processes of DNA damage induced cell fate and predicting the effectiveness of DNA damage related medical interventions at the cellular level.

The application of pneumatic jigging in the recovery of metallic fraction from shredded printed wiring boards.

Waste electrical and electronic equipment (WEEE) is one of the fastest growing waste streams worldwide with volumes increasing by 40% each year. WEEE has attracted increasing concern worldwide due to its high metal content and the potential environmental threat which results from uncontrolled recycling practices. Innovative physical separation techniques for WEEE recycling are preferential compared with chemical methods because of the reduction of energy and chemical consumption as well as potential environmental threats. Pneumatic jigging is a dry separation process capable of achieving good separation of coarse material within a very narrow density range, which makes it suitable as a pretreatment process for WEEE recycling. The work presented in this paper investigates the potential application of pneumatic jigging in metal recovery from WEEE. A pilot scale pneumatic jig has been developed by University of Nottingham Ningbo to separate shredded printed wiring boards into two streams: a light fraction (mainly non-metallic fraction consisting of glass fiber, fluffs, and plastic pieces) and dense fraction (metallic fraction). The novelty of work presented in this paper is the application of a dry separation technique in WEEE recycling for metal recovery. Compared with conventional wet separation processes involved in WEEE recycling industry, dry separation has the advantage of zero secondary pollution. The results of this experimental program show pneumatic jigging to be an effective and environmental friendly technique as a pretreatment process for the recovery of the metallic fraction from shredded WEEE.

Ternary Dry Powder Agglomerate Inhalation Formulation of Melatonin With Air Jet Mixing to Improve In Vitro And In Vivo Performance.

An improved agglomerate formulation with melatonin and fine lactose for dry powder inhalation using Turbuhaler® was developed. Co-grinding lactose with 1 % magnesium stearate prior to air jet mixing served as a key factor to improve the in vitro aerosolization and in vivo efficacy. Elevated mixing pressure facilitated the dispersion and homogenization of the cohesive mixture for even distribution of agglomerate size after spheroidization and subsequent higher emitted dose with lower variation. Magnesium stearate was employed as a tertiary component to adjust the interparticle force for better aerosolization. At optimized mixing pressure, co-grinding lactose with magnesium stearate before jet mixing displayed further improvement of fine particle fraction to 71.6 ± 3.1 %. The superior fine particle deposition efficiency contributed to rapid onset of action and a high bioavailability of 67.0 % after intratracheal administration to rats. Overall, an inhalable melatonin dry powder formulation exhibiting good aerosol property and lung deposition with clinical translation potential was developed.

Improving Inhalation Performance with Particle Agglomeration via Combining Mechanical Dry Coating and Ultrasonic Vibration.

Agglomerate formulations for dry powder inhalation (DPI) formed with fine particles are versatile means for the highly efficient delivery of budesonide. However, uncontrolled agglomeration induces high deposition in the upper airway, causing local side effects due to high mechanical strength, worse deagglomeration, and poor fine-particle delivery. In the present study, fine lactose was mechanically dry-coated prior to particle agglomeration, and the agglomerates were then spheroidized via ultrasonic vibration to improve their aerosol performance. The results showed that the agglomerate produced with the surface-enriched hydrophobic magnesium stearate and ultrasonic vibration demonstrated improved aerosolization properties, benefiting from their lower mechanical strength, less interactive cohesive force, and improved fine powder dispersion behavior. After dispersion utilizing a Turbuhaler® with a pharmaceutical cascade impactor test, a fine particle fraction (FPF) of 71.1 ± 1.3% and an artificial throat deposition of 19.3 ± 0.4% were achieved, suggesting the potential to improve the therapeutic outcomes of budesonide with less localized infections of the mouth and pharynx.

A feeding jejunostomy causing an intussusception - case report and literature review.

Use of enteral nutrition has increased dramatically over the past two decades due to improved nutritional formulas, better quality feeding tubes and the ability to use less invasive endoscopic, fluoroscopic and laparoscopic techniques. Intussusception accounts for 1-5% of adult intestinal obstructions, with feeding tubes acting as a lead point in < 1% of cases. Since intussusception is rare, especially in adults, it is not always considered in the initial differential diagnosis of patients presenting with abdominal pain, nausea, vomiting or constipation. If left untreated, intussusception can eventually lead to bowel compromise, poor outcomes and even death. Therefore, prompt recognition and correction are necessary. We present a case of small bowel obstruction in an elderly male secondary to a tube-related intussusception. A review of the signs, symptoms and treatment recommendations is provided.

Sol/Antisolvent Coating for High Initial Coulombic Efficiency and Ultra-stable Mechanical Integrity of Ni-Rich Cathode Materials.

The Ni-rich cathode holds great promise for high energy density lithium-ion batteries because of its high capacity and operating voltage. However, crucial problems such as cation disorder, structural degradation, side reactions, and microcracks become serious with increasing nickel content. Herein, a novel and facile sol/antisolvent coating modification of Ni-rich layered oxide LiNi0.85Co0.1Mn0.05O2 (NCM) is developed where we use ethanol to disperse the nanosized LiBO2 to form the sol and adopt tetrahydrofuran (THF) as antisolvent to prepare the cluster of nanoparticles to be coated on the surface of NCM. The coating thickness can be tuned through the THF addition amount. The LiBO2 nanorod deposition is formed as well over the crack of the NCM cathode, likely acting as a patch to repair the original defect of the intrinsic crack. The uniform LiBO2 nanospherical particle coating together with LiBO2 nanorod wrapping provides a double protection against electrolytes. Compared with the raw material, LiBO2-coated LiNi0.85Co0.1Mn0.05O2 (LiBO2-coated NCM) exhibits a high initial Coulombic efficiency of 90.3% at 0.2 C between 2.8 and 4.3 V vs Li+/Li, a superior rate capability, enhanced fast charge property at 3 C, and restricted microcrack formation. This simple in-site modification and repairing technology guarantees a good mechanical integrity of the polycrystalline Ni-rich cathode.

The characterisation and provenance of crude oils stranded on the South Australian coastline. Part I: Oil types and their weathering.

Semi-solid crude oil has been known to wash ashore along the South Australian coastline for over 120 years. The early reports pre-date offshore petroleum exploration and tanker shipping activities in Australian waters, suggesting that this stranded oil originates from natural offshore seepage. Three physically distinct varieties are represented: waxy bitumen, asphaltite and tar. In order to distinguish this natural "background" contamination of the coastline from any potential anthropogenic sources of petroleum, such as oil spills, whole-oil GC-MS analysis was employed to identify at least seven geochemically different types of stranded oil, based on a suite of 633 specimens collected from the coastline during three annual surveys of 30 ocean beaches between 2014 and 2016. The waxy bitumens, which in terms of their biomarker alkanes display an atypical pattern of alteration due to weathering in the marine environment, are more severely altered than similar specimens collected 25 years ago.

The natural hydrocarbon loading of the South Australian coastline.

Crude oil released from natural offshore seeps may strand in coastal environments. Understanding the different types of oil which accumulate on a given coastline, in addition to their spatial distribution and abundance, may be used to establish an environmental baseline for natural "background" petroleum contamination. Here we summarise the hydrocarbon loading of thirty beaches on Australia's southern margin based on three annual surveys in 2014-2016. Comparison with the results of surveys conducted in 1990 and 1991 reveals a marked reduction in hydrocarbon loading. Furthermore, modern samples of the most commonly encountered oil, attributed to a lacustrine petroleum system in the Indonesian Archipelago, are significantly more degraded than those of prior studies. We attribute this reduction in hydrocarbon loading to prolonged oil production in Southeast Asia, which in turn results in reduced reservoir pressures and the eventual cessation of formerly active offshore seepage.

The characterisation and provenance of crude oils stranded on the South Australian coastline. Part II: Potential parent petroleum systems.

In 2014-2016 more than 600 specimens of semi-solid crude oil were recovered from 30 ocean beaches along the coastline of South Australia, as part of the recently completed Great Australian Bight Research Program. All are believed to be products of submarine oil seepage. Their source-specific biomarker signatures provide the basis for their assignment to sixteen oil families, some previously unrecognised. Two of these families (asphaltite and asphaltic tar) likely originated from Cretaceous marine source rocks in the offshore Bight Basin. The others comprise waxy oils of lacustrine, fluvio-deltaic and marine source affinity. Their biomarker characteristics do not match those of any Australian crude oil. However, they are strikingly similar to those of oils found in Cenozoic and Mesozoic basins throughout the Indonesian Archipelago and elsewhere in Southeast Asia.

Toxicities of gemcitabine in patients with severe hepatic dysfunction.

OBJECTIVE: To determine the relationship between doses of gemcitabine and absolute neutrophil count and thrombocytopenia in patients with severe hepatic dysfunction (total bilirubin > or =4.5 mg/dL), and the relationship between doses of gemcitabine in patients with severe hepatic dysfunction and nonhematologic toxicity. CASE SUMMARY: A retrospective chart review was conducted for patients receiving gemcitabine at the Medical University of South Carolina from October 2006 through October 2008. Seven patients were identified who had an elevated total bilirubin level (> or =4.5 mg/dL) at the time they were receiving gemcitabine. All 7 patients received gemcitabine 1000 mg/m(2) throughout their treatment, regardless of liver function. Six patients did not experience significant hematologic toxicity warranting a dose reduction or a dose being held. One patient developed thrombocytopenia, warranting a dose being held. DISCUSSION: Gemcitabine is a chemotherapy agent frequently used for the treatment of pancreatic cancer as well as metastatic breast, lung, and ovarian cancer. To date there is limited information on dosing of gemcitabine in patients with an elevated total bilirubin. A previous study looking at lower grades of liver dysfunction suggested empiric dose reductions be made in these patients because of increased incidence of toxicity. CONCLUSIONS: These results indicate the possibility that no initial dose reduction is necessary for patients with liver dysfunction receiving gemcitabine; however, close monitoring of these patients is required.

Incidence of vancomycin-resistant enterococci (VRE) infection in high-risk febrile neutropenic patients colonized with VRE.

PURPOSE: This study seeks to determine the incidence of vancomycin-resistant enterococci (VRE) infection in high-risk neutropenic fever patients colonized with VRE and to determine patient characteristics associated with VRE infection. METHODS: We conducted a retrospective, single-center, unmatched case-control study. Fifty-three VRE-colonized, high-risk patients with neutropenic fever were identified between January 2006 and February 2009. The two most common diagnoses/conditions included acute myeloid leukemia and hematopoietic stem cell transplantation. Data collected included days of neutropenia, days of fever, demographic data, culture results, and antimicrobial therapy. RESULTS: Twenty of the 53 patients (38%) with VRE colonization developed a VRE infection. The most common VRE infections were bacteremias (26%). The presence of neutropenia lasting longer than 7 days was associated with the development of VRE infection in this high-risk population colonized with VRE. The timeframe to develop VRE infection varied from 1 day to 2 weeks. CONCLUSION: For patients colonized with VRE, approximately 38% of high-risk neutropenic patients developed a VRE infection. This is the first study to specifically evaluate the incidence of VRE infections in febrile neutropenic patients colonized with VRE. Future research into the use and efficacy of empiric VRE coverage is needed.

Exploring "Internet+Recycling": Mass balance and life cycle assessment of a waste management system associated with a mobile application.

Individual users cannot readily access the collection channels is a persistent problem in municipal solid waste (MSW) management, resulting in low MSW collection rates. A new waste management model, "Internet+Recycling", has come into being; this model enables individuals to arrange collection appointment through various online platforms, then the collectors pick up the waste on-site. It is believed that "Internet+Recycling" can be a solution to mitigate the collection barrier in MSW management, as it provides individuals a convenient access to formal waste management systems. However, whether this emerging MSW collection model would bring environmental benefits is yet unknown. We here quantitatively examine the mass balance and environmental performance of MSW recycling associated with the use of such a "Internet+Recycling" mobile application - Aibolv. All transactions occurred on the mobile application within a period of six monthare included, and all related activities are modeled using the methodology that combines material flow analysis (MFA) and life cycle assessment (LCA). According to the extant MSW management legislation in China, we classify the collected MSW into three categories, subsidized waste electric and electronic equipment (WEEE) like television and refrigerator - T1, unsubsidized WEEE like mobile phone - T2, and other recyclables like paper and fabric - T3. The MFA results show that plastics and common metals are the dominate secondary material streams, and glass, precious metals and battery metals are mainly recovered from WEEE. The LCA results indicate that the disposal of the T2 waste has the highest environmental savings, due to the recovery of precious metals. Increased remanufacturing rates impart negative impacts, while increments in the quantity of spent mobile phones could significantly improve overall environmental performance. Based on the acquired results, recommendations are provided for facilitating the future development of "Internet+Recycling", and limitations of this work are identified as well.

Remotely constraining the temporal evolution of offshore oil systems.

An understanding of the temporal evolution of a petroleum system is fundamental to interpreting where hydrocarbons may be trapped in the subsurface. However, traditional exploration methods provide few absolute constraints on the timing of petroleum generation. Here we show that 187Re/187Os geochronology may be applied to natural crude oil seepage to determine when petroleum generation occurred in offshore sedimentary basins. Using asphaltites collected from the South Australian coastline, our determined Re-Os age (68 ± 15 million years ago) is consistent with their derivation from a Late Cretaceous source rock in the nearby Bight Basin, an interpretation similarly favoured by source-specific biomarker constraints. Furthermore, the calculated initial 187Os/188Os composition of the asphaltites, a value inherited from the source rock at the time of oil generation, suggests that the source rock represents the later stage of Oceanic Anoxic Event 2. Our results demonstrate a new approach to identifying the origin of crude oils encountered in coastal environments by providing direct constraints on the timing of petroleum generation and potential source rock intervals in poorly characterised offshore sedimentary basins prior to exploratory drilling.

The Report of the 2018-2019 Professional Affairs Standing Committee: The Role of Educators in Pharmacy Practice Transformation.

The 2018-2019 Professional Affairs Committee examined the potential roles and needs of clinical educators (faculty and preceptors) in leading transformation in pharmacy practice. The committee was charged to (1) discuss the potential roles and responsibilities of faculty and preceptors leading transformation and enhanced patient care services in pharmacy practice; (2) describe factors, including clinician well-being and resilience, which may influence faculty and preceptor involvement in practice transformation and the enhancement of patient care services; and (3) recommend how the efforts and successes of faculty and preceptors involved in pharmacy practice transformation can be replicated and recognized as well as identify the types of continuing professional development (CPD) that should be available to enable the influence and implementation of patient care services. This report provides a framework for addressing the committee charges by examining the roles of advocacy, collaboration, continuing professional development, and clinician resilience and well-being. The committee provides a revision to a current AACP policy regarding continuing professional development as well as several recommendations to AACP and suggestions to colleges and schools of pharmacy pertaining to the committee charges.

Relation of Pregnancy Loss to Risk of Cardiovascular Disease in Parous Postmenopausal Women (From the Women's Health Initiative).

Women with history of pregnancy loss (PL) have higher burden of cardiovascular disease (CVD) later in life, yet it is unclear whether this is attributable to an association with established CVD risk factors (RFs). We examined whether PL is associated with CVD RFs and biomarkers in parous postmenopausal women in the Women's Health Initiative, and whether the association between PL and CVD RFs accounted for the association between PL and incident CVD. Linear and logistic regressions were used to estimate associations between baseline history of PL and CVD RFs. Cox proportional hazards regression models were used to estimate the associations between baseline history of PL and incident CVD after adjustment for baseline RFs. Of 79,121 women, 27,272 (35%) had experienced PL. History of PL was associated with higher body mass index (p < 0.0001), hypertension (p < 0.0001), diabetes (p = 0.003), depression (p < 0.0001), and lower income (p < 0.0001), physical activity (p = 0.01), poorer diet (p < 0.0001), smoking (p < 0.0001), and alcohol use (p < 0.0001). After adjustment for CVD RFs, PL was significantly associated with incident CVD over mean follow up of 16 years (hazard ratio 1.11, 95% confidence interval 1.06 to 1.16). In conclusion, several CVD RFs are associated with PL, but they do not entirely account for the association between PL and incident CVD.

Outcomes of Veterans Undergoing TAVR Within Veterans Affairs Medical Centers: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program.

OBJECTIVES: This study sought to describe clinical and procedural characteristics of veterans undergoing transcatheter aortic valve replacement (TAVR) within U.S. Department of Veterans Affairs (VA) centers and to examine their association with short- and long-term mortality, length of stay (LOS), and rehospitalization within 30 days. BACKGROUND: Veterans with severe aortic stenosis frequently undergo TAVR at VA medical centers. METHODS: Consecutive veterans undergoing TAVR between 2012 and 2017 were included. Patient and procedural characteristics were obtained from the VA Clinical Assessment, Reporting, and Tracking system. The primary outcomes were 30-day and 1-year survival, LOS >6 days, and rehospitalization within 30 days. Logistic regression and Cox proportional hazards analyses were performed to evaluate the associations between pre-procedural characteristics and LOS and rehospitalization. RESULTS: Nine hundred fifty-nine veterans underwent TAVR at 8 VA centers during the study period, 860 (90%) by transfemoral access, 50 (5%) transapical, 36 (3.8%) transaxillary, and 3 (0.3%) transaortic. Men predominated (939 of 959 [98%]), with an average age of 78.1 years. There were 28 deaths within 30 days (2.9%) and 134 at 1 year (14.0%). Median LOS was 5 days, and 141 veterans were rehospitalized within 30 days (14.7%). Nonfemoral access (odds ratio: 1.74; 95% confidence interval [CI]: 1.10 to 2.74), heart failure (odds ratio: 2.51; 95% CI: 1.83 to 3.44), and atrial fibrillation (odds ratio: 1.40; 95% CI: 1.01 to 1.95) were associated with increased LOS. Atrial fibrillation was associated with 30-day rehospitalization (hazard ratio: 1.79; 95% CI: 1.22 to 2.63). CONCLUSIONS: Veterans undergoing TAVR at VA centers are predominantly elderly men with significant comorbidities. Clinical outcomes of mortality and rehospitalization at 30 days and 1-year mortality compare favorably with benchmark outcome data outside the VA.

Shrinkage of cutaneous specimens: formalin or other factors involved?

BACKGROUND: Shrinkage of cutaneous tissue during processing is a source of controversy. This study was designed to prospectively determine tissue shrinkage at two intervals: 1 min after excision and after 24 to 48 h of formalin fixation. Secondarily, gender, age, site, prior biopsy scar and solar elastosis were evaluated with respect to shrinkage. METHODS: Ninety-seven cutaneous specimens were measured prior to excision, 1 min after removal and after 24 to 48 h of formalin fixation. Width of prior biopsy scar, damage to elastic fibers and solar elastosis were subjectively quantified. RESULTS: Significant tissue shrinkage occurred immediately after excision, prior to formalin fixation. Mean shrinkage (95% confidence interval): length 20.66% +/- 2.15% and width 11.79% +/- 2.35%. Range of shrinkage: length 0 to 41.18% and width -18.75% (indicating expansion) to 37.50%. Patient age was significant; shrinkage decreased 0.3% per year of increasing age. Site was less significant; trunk excisions measured 5% greater shrinkage than head/neck excisions. As solar elastosis increased, shrinkage decreased. CONCLUSIONS: Cutaneous tissue shrinkage following excision is primarily because of intrinsic tissue contractility. Increasing patient age and solar elastosis correlate with less shrinkage. The clinicians and dermatopathologists must be cognizant of the expected shrinkage of submitted specimens for settling discrepancies within the medical record.