Biochar has been recently heralded as an amendment to revitalize degraded soils, improve soil carbon sequestration, increase agronomic productivity and enter into future carbon trading markets. ...However, scientific and economic technicalities may limit the ability of biochar to consistently deliver on these expectations. Past research has demonstrated that biochar is part of the black carbon continuum with variable properties, due to the net result of production (e.g., feedstock and pyrolysis conditions) and post-production factors (storage or activation). Therefore, biochar is not a single entity, but rather spans a wide range of black carbon forms. Biochar is black carbon, but not all black carbon is biochar. Agronomic benefits arising from biochar additions to degraded soils have been emphasized, but negligible and negative agronomic effects have also been reported. Fifty percent of the reviewed studies reported yield increases following black carbon or biochar additions, with the remainder of the studies reporting alarming decreases to no significant differences. Hardwood biochar (black carbon) produced by traditional methods (kilns or soil pits) possessed the most consistent yield increases when added to soils. The universality of this conclusion requires further evaluation due to the highly skewed feedstock preferences within existing studies. With global population expanding while the amount of arable land remains limited, restoring soil quality to nonproductive soils could be a vital key to meeting future global food production, food security and energy supplies; biochar may play a role in this endeavor. Biochar economics are often marginally viable and are tightly tied to the assumed duration of agronomic benefits. Further research is needed to determine the specific conditions under which biochar can provide real economic and agronomic benefits and to elucidate the fundamental mechanisms responsible for these benefits.
Organ injury and impairment are commonly observed in patients with acute heart failure (AHF), and congestion is an essential pathophysiological mechanism of impaired organ function. Congestion is the ...predominant clinical profile in most patients with AHF; a smaller proportion presents with peripheral hypoperfusion or cardiogenic shock. Hypoperfusion further deteriorates organ function. The injury and dysfunction of target organs (i.e. heart, lungs, kidneys, liver, intestine, brain) in the setting of AHF are associated with increased risk for mortality. Improvement in organ function after decongestive therapies has been associated with a lower risk for post‐discharge mortality. Thus, the prevention and correction of organ dysfunction represent a therapeutic target of interest in AHF and should be evaluated in clinical trials. Treatment strategies that specifically prevent, reduce or reverse organ dysfunction remain to be identified and evaluated to determine if such interventions impact mortality, morbidity and patient‐centred outcomes. This paper reflects current understanding among experts of the presentation and management of organ impairment in AHF and suggests priorities for future research to advance the field.
Pilocytic astrocytomas (PAs), WHO malignancy grade I, are the most frequently occurring central nervous system tumour in 5- to 19-year-olds. Recent reports have highlighted the importance of MAPK ...pathway activation in PAs, particularly through a tandem duplication leading to an oncogenic BRAF fusion gene. Here, we report two alternative mechanisms resulting in MAPK activation in PAs. Firstly, in striking similarity to the common BRAF fusion, tandem duplication at 3p25 was observed, which produces an in-frame oncogenic fusion between SRGAP3 and RAF1. This fusion includes the Raf1 kinase domain, and shows elevated kinase activity when compared with wild-type Raf1. Secondly, a novel 3 bp insertion at codon 598 in BRAF mimics the hotspot V600E mutation to produce a transforming, constitutively active BRaf kinase. Although these two alterations are not common, they bring the number of cases with an identified 'hit' on the Ras/Raf-signalling pathway to 36 from our series of 44 (82%), confirming its central importance to the development of pilocytic astrocytomas.
Abstract
CRISPR-based gene drives offer promising means to reduce the burden of pests and vector-borne diseases. These techniques consist of releasing genetically modified organisms carrying ...CRISPR-Cas nucleases designed to bias their inheritance and rapidly propagate desired modifications. Gene drives can be intended to reduce reproductive capacity of harmful insects or spread anti-pathogen effectors through wild populations, even when these confer fitness disadvantages. Technologies capable of halting the spread of gene drives may prove highly valuable in controlling, counteracting, and even reverting their effect on individual organisms as well as entire populations. Here we show engineering and testing of a genetic approach, based on the germline expression of a phage-derived anti-CRISPR protein (AcrIIA4), able to inactivate CRISPR-based gene drives and restore their inheritance to Mendelian rates in the malaria vector
Anopheles gambiae
. Modeling predictions and cage testing show that a single release of male mosquitoes carrying the AcrIIA4 protein can block the spread of a highly effective suppressive gene drive preventing population collapse of caged malaria mosquitoes.
Stereotactic body radiation therapy (SBRT) delivers fewer high-dose fractions of radiation which may be radiobiologically favorable to conventional low-dose fractions commonly used for prostate ...cancer radiotherapy. We report our early experience using SBRT for localized prostate cancer.
Patients treated with SBRT from June 2008 to May 2010 at Georgetown University Hospital for localized prostate carcinoma, with or without the use of androgen deprivation therapy (ADT), were included in this retrospective review of data that was prospectively collected in an institutional database. Treatment was delivered using the CyberKnife® with doses of 35 Gy or 36.25 Gy in 5 fractions. Biochemical control was assessed using the Phoenix definition. Toxicities were recorded and scored using the CTCAE v.3. Quality of life was assessed before and after treatment using the Short Form-12 Health Survey (SF-12), the American Urological Association Symptom Score (AUA) and Sexual Health Inventory for Men (SHIM) questionnaires. Late urinary symptom flare was defined as an AUA score ≥ 15 with an increase of ≥ 5 points above baseline six months after the completion of SBRT.
One hundred patients (37 low-, 55 intermediate- and 8 high-risk according to the D'Amico classification) at a median age of 69 years (range, 48-90 years) received SBRT, with 11 patients receiving ADT. The median pre-treatment prostate-specific antigen (PSA) was 6.2 ng/ml (range, 1.9-31.6 ng/ml) and the median follow-up was 2.3 years (range, 1.4-3.5 years). At 2 years, median PSA decreased to 0.49 ng/ml (range, 0.1-1.9 ng/ml). Benign PSA bounce occurred in 31% of patients. There was one biochemical failure in a high-risk patient, yielding a two-year actuarial biochemical relapse free survival of 99%. The 2-year actuarial incidence rates of GI and GU toxicity ≥ grade 2 were 1% and 31%, respectively. A median baseline AUA symptom score of 8 significantly increased to 11 at 1 month (p=0.001), however returned to baseline at 3 months (p=0.60). Twenty one percent of patients experienced a late transient urinary symptom flare in the first two years following treatment. Of patients who were sexually potent prior to treatment, 79% maintained potency at 2 years post-treatment.
SBRT for clinically localized prostate cancer was well tolerated, with an early biochemical response similar to other radiation therapy treatments. Benign PSA bounces were common. Late GI and GU toxicity rates were comparable to conventionally fractionated radiation therapy and brachytherapy. Late urinary symptom flares were observed but the majority resolved with conservative management. A high percentage of men who were potent prior to treatment remained potent two years following treatment.
Pathogens rarely cause extinctions of host species, and there are few examples of a pathogen changing species richness and diversity of an ecological community by causing local extinctions across a ...wide range of species. We report the link between the rapid appearance of a pathogenic chytrid fungus Batrachochytrium dendrobatidis in an amphibian community at El Copé, Panama, and subsequent mass mortality and loss of amphibian biodiversity across eight families of frogs and salamanders. We describe an outbreak of chytridiomycosis in Panama and argue that this infectious disease has played an important role in amphibian population declines. The high virulence and large number of potential hosts of this emerging infectious disease threaten global amphibian diversity.
Enhanced half‐life factor VIII and IX products are being introduced into routine clinical practice. Published data report on clinical trials and there are limited data available on how to use these ...products in routine clinical practice. Many patients, for example, those with a past history of an inhibitor, have been excluded from clinical trials and there are limited data published on children. This guidance document is a consensus statement from the UK Haemophilia Centres Doctors' Organisation and aims to give pragmatic advice on the use of these products in routine practice.
Objective
To ascertain the incidence of massive transfusion (MT) in obstetrics in the UK, and describe its management and clinical outcomes.
Design
A population‐based cross‐sectional study conducted ...through the UK Obstetric Surveillance System (UKOSS).
Settings
All UK hospitals with consultant‐led maternity units.
Population
Any pregnant woman at ≥20 weeks of gestation receiving ≥8 units of red blood cells within 24 hours of giving birth, from July 2012 to June 2013.
Methods
Prospective case identification through the monthly mailing of UKOSS.
Results
We identified 181 women who had undergone MT, making the estimated incidence of MT associated with postpartum haemorrhage (PPH) 23 per 100 000 maternities (95% confidence interval 19–26) per year. The median estimated blood loss was 6 l (interquartile range 4.5–8.0 l). The majority of women presented outside working hours (63%), 40% had had previous caesarean sections and 3% had normal vaginal births without risk factors. The main cause for MT was uterine atony (40%) and the main mode of birth was caesarean section (69%). Of the 181 women, 15 received >20 units of red blood cells. In total, 45% of women underwent hysterectomy, and among all causes of PPH, placenta accreta had the highest hysterectomy rate. Two women died, 82% were admitted to intensive care/high‐dependency units, and 28% developed major morbidities.
Conclusion
Massive transfusion due to PPH is associated with high rates of morbidity and hysterectomy. Clinical and research efforts should focus on approaches to recognise and optimise timely resuscitation and management of these severe cases.
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Massive transfusion due to postpartum haemorrhage is associated with high rates of morbidity and hysterectomy.
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Massive transfusion due to postpartum haemorrhage is associated with high rates of morbidity and hysterectomy.
Postpartum haemorrhage (PPH) can be exacerbated by haemostatic failure. Based on data from trauma studies, empirical infusions of fresh frozen plasma (FFP) are often given during severe PPH if ...coagulation tests are unavailable. This study observed a cohort of women with moderate/severe PPH in whom FFP infusion was guided by the use of viscoelastometric point-of-care testing (VE-POCT) and clinical assessment.
Women were enrolled into this observational study when blood loss was measured or suspected to be about 1000 mL. If Fibtem A5 determined by Rotem® thromboelastometry remained >15 mm, or bleeding stopped, FFP was withheld. If Fibtem A5 was ≤15 mm and bleeding ongoing, women were randomized into an interventional study as previously reported. Clinical and laboratory outcomes were recorded.
The study recruited 605 women and 98% had FFP withheld. The median (25th–75th centile) total blood loss was 1500 (1300–2000) mL with 300 (50–545) mL occurring after enrolment. Total blood loss was >2500 mL in 40/605 (6.6%) women. RBCs were transfused in 141/605 (23.3%) patients and 11 (1.8%) received ≥4 units. At least one invasive procedure was performed in 283/605 (46.8%) women. Level 3 care was required for 10/605 (1.7%) women. No women developed clinically significant haemostatic impairment.
Restrictive use of FFP guided by clinical assessment of bleeding and VE-POCT is feasible and did not result in clinically significant haemostatic impairment. Studies should compare the clinical and cost effectiveness of empirical FFP infusions, according to current guidelines, with targeted use of FFP based on VE-POCT.
ISRCTN46295339 (http://www.isrctn.com/ISRCTN46295339) (accessed July 24, 2017), EudraCT 2012-005511-11 (https://www.clinicaltrialsregister.eu/ctr-search?query=2011-005511-11) (accessed July 24, 2017).
Linked ContentThis article is linked to Bonovas et al papers. To view these articles visit https://doi.org/10.1111/apt.14023 and https://doi.org/10.1111/apt.14084.
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