Assessing temperature-based adaptation limits to climate change of temperate perennial fruit crops.

Temperate perennial fruit and nut trees play varying roles in world food diversity-providing edible oils and micronutrient, energy, and protein dense foods. In addition, perennials reuse significant amounts of biomass each year providing a unique resilience. But they also have a unique sensitivity to seasonal temperatures, requiring a period of dormancy for successful growing season production. This paper takes a global view of five temperate tree fruit crops-apples, cherries, almonds, olives, and grapes-and assesses the effects of future temperature changes on thermal suitability. It uses climate data from five earth system models for two CMIP6 climate scenarios and temperature-related indices of stress to indicate potential future areas where crops cannot be grown and highlight potential new suitable regions. The loss of currently suitable areas and new additions in new locations varies by scenario. In the southern hemisphere (SH), end-century (2081-2100) suitable areas under the SSP 5-8.5 scenario decline by more than 40% compared to a recent historical period (1991-2010). In the northern hemisphere (NH) suitability increases by 20% to almost 60%. With SSP1-2.6, however, the changes are much smaller with SH area declining by about 25% and NH increasing by about 10%. The results suggest substantial restructuring of global production for these crops. Essentially, climate change shifts temperature-suitable locations toward higher latitudes. In the SH, most of the historically suitable areas were already at the southern end of the landmass limiting opportunities for adaptation. If breeding efforts can bring chilling requirements for the major cultivars closer to that currently seen in some cultivars, suitable areas at the end of the century are greater, but higher summer temperatures offset the extent. The high value of fruit crops provides adaptation opportunities such as cultivar selection, canopy cooling using sprinklers, shade netting, and precision irrigation.

Variability in endometrial carcinoma pathology practice: opportunities for improvement with molecular classification.

We assessed the landscape of diagnostic pathology practice and how molecular classification could potentially impact management of patients with endometrial cancer by collecting patient samples, clinicopathologic data, and patient outcomes from EC patients diagnosed in 2016 at 10 Canadian tertiary cancer centers and 19 community hospitals. ProMisE molecular subtype (POLEmut, MMRd, p53abn, No Specific Molecular Profile (NSMP)) was assigned retrospectively. 1357 patients were fully evaluable including 85 POLEmut (6.3%), 380 MMRd (28.0%), 643 NSMP (47.4%), and 249 p53abn ECs (18.3%). Immunohistochemistry (IHC) for MMR proteins was undertaken at the time of primary diagnosis in 2016 in only 42% of the cohort (570/1357; range 3.5-95.4%/center). p53 IHC had only been performed in 21.1% of the cohort (286/1357; range 10.1-41.9%/center). Thus, based on the retrospective molecular subtype assignment, 54.7% (208/380) of MMRd EC had not been tested with MMR IHC (or MSI) and 48.2% (120/249) of p53abn ECs were not tested with p53 IHC in 2016. Molecular subtype diversity within histotypes was profound; most serous carcinomas were p53abn (91.4%), but only 129/249 (51.8%) p53abn EC were serous. Low-grade (Gr1-2) endometrioid carcinomas were mostly NSMP (589/954, 61.7%) but included all molecular subtypes, including p53abn (19/954, 2.0%). Molecular subtype was significantly associated with clinical outcomes (p < 0.001) even in patients with stage I disease (OS p = 0.006, DSS p < 0.001, PFS p < 0.001). Assessment of national pathologic practice in 2016 shows highly variable use of MMR and p53 IHC and demonstrates significant opportunities to improve and standardize biomarker reporting. Inconsistent, non-reflexive IHC resulted in missed opportunities for Hereditary Cancer Program referral and Lynch Syndrome diagnosis, and missed potential therapeutic implications (e.g., chemotherapy in p53abn EC, immune blockade for MMRd EC). Routine integration of molecular subtyping into practice can improve the consistency of EC pathology assessment and classification.

Climate change and Australia's primary industries: factors hampering an effective and coordinated response.

Australia's primary production sector operates in one of the world's most variable climates with future climate change posing a challenge to its ongoing sustainability. Recognising this, Australia has invested in understanding climate change risks to primary production with a substantial amount of research produced. Recently, focus on this research space has broadened, with interests from the financial sector and expanded scopes of works from government and industry. These expanded needs require sector- and country-wide assessments to assist with the implementation of climate strategies. We considered the applicability of the current research body for these needs by reviewing 188 peer-reviewed studies that considered the quantitative impacts of climate change on Australia's primary industries. Our broad review includes cropping, livestock, horticulture, forestry and fisheries and biosecurity threats. This is the first such review for Australia, and no other similar country-wide review was found. We reviewed the studies through three lenses, industry diversity, geographic coverage and study comparability. Our results show that all three areas are lacking for sector- and country-wide assessments. Industry diversity was skewed towards cropping and biosecurity threats (64% of all studies) with wheat in particular a major focus (25% of all studies). Geographic coverage at a state level appeared to be evenly distributed across the country; however, when considered in conjunction with industry focus, gaps emerged. Study comparability was found to be very limited due to the use of different historical baseline periods and different impact models. We make several recommendations to assist with future research directions, being (1) co-development of a standard set of method guidelines for impact assessments, (2) filling industry and geographic knowledge gaps, and (3) improving transparency in study method descriptions. Uptake of these recommendations will improve study application and transparency enabling and enhancing responses to climate change in Australia's primary industries.

Extracellular vesicle secretion of miR-142-3p from lung adenocarcinoma cells induces tumor promoting changes in the stroma through cell-cell communication.

Extracellular vesicles (EVs) are mediators of communication between cancer cells and the surrounding tumor microenvironment. EV content is able to influence key tumorigenic changes including invasion, metastasis, and inducing pro-tumor changes in the stroma. MiR-142-3p is a known tumor suppressor in LAC and was recently shown to be enriched within LAC EVs, indicating its potential as a key signaling miRNA. Our research demonstrates the role EV associated miR-142-3p plays when transferred from LAC cells to both endothelial and fibroblast cells. We demonstrate that transfer of miR-142-3p in LAC EVs to endothelial cells promotes angiogenesis through inhibition of TGFßR1. Additionally, we show EV associated miR-142-3p promotes the cancer-associated fibroblast phenotype in lung fibroblast cells which we show is independent of TGFß signaling. These findings suggest that miR-142-3p within LAC EVs can be transferred from LAC cells to both endothelial and fibroblast cells to promote tumor associated changes.

Divergent Elementoboration: 1,3-Haloboration versus 1,1-Carboboration of Propargyl Esters.

This work showcases the 1,3-haloboration reaction of alkynes in which boron and chlorine add to propargyl systems in a proposed sequential oxazoliumborate formation with subsequent ring-opening and chloride migration. In addition, the functionalization of these propargyl esters with dimethyl groups in the propargylic position leads to stark differences in reactivity whereby a formal 1,1-carboboration prevails to give the 2,2-dichloro-3,4-dihydrodioxaborinine products as an intramolecular chelate. Density functional theory calculations are used to rationalize the distinct carboboration and haloboration pathways. Significantly, this method represents a metal-free route to highly functionalized compounds in a single step to give structurally complex products.

Tris(2,4,6-trifluorophenyl)borane: An Efficient Hydroboration Catalyst.

The metal-free catalyst tris(2,4,6-trifluorophenyl)borane has demonstrated its extensive applications in the 1,2-hydroboration of numerous unsaturated reagents, namely alkynes, aldehydes and imines, consisting of a wide array of electron-withdrawing and donating functionalities. A range of over 50 borylated products are reported, with many reactions proceeding with low catalyst loading under ambient conditions. These pinacol boronate esters, in the case of aldehydes and imines, can be readily hydrolyzed to leave the respective alcohol and amine, whereas alkynyl substrates result in vinyl boranes. This is of great synthetic use to the organic chemist.

Tris(pentafluorophenyl)borane and Beyond: Modern Advances in Borylation Chemistry.

As main-group chemistry, in particular boron chemistry, has expanded and developed over the past 20 years, one reagent has risen to prominence as well. Tris(pentafluorophenyl)borane, B(C6F5)3 (commonly known as BCF), has demonstrated extensive applications in a wide variety of reactions, including borylation, hydrogenation, hydrosilylation, frustrated Lewis pair (FLP) chemistry, Lewis acid catalysis, and more. The high Lewis acidity of B(C6F5)3 is derived from the electronic effects of its three C6F5 rings, rendering it a versatile reagent for a great number of reactions. In addition, the steric bulk of these rings also allows it to function as the Lewis acid in a FLP, granting this reagent yet another synthetically useful application. However, as main-group chemistry continues to evolve as a field, new reagents are required that go beyond BCF, increasing not only the range of reactions available but also the breadth of compounds attainable. Great strides have already been made in order to accomplish this task, and this review will highlight modern advances in boron chemistry relating to borylation reactions. Herein, we will show the recent uses of B(C6F5)3 in borylation reactions while also focusing on current advances in novel borane and borocation usage that eclipses that of the stalwart B(C6F5)3.

Five-year follow-up of a randomized, controlled trial comparing saphenofemoral ligation and stripping of the great saphenous vein with endovenous laser ablation (980 nm) using local tumescent anesthesia.

OBJECTIVE: The objective of this study was to compare the long-term results (groin-related recurrence, great saphenous vein [GSV] occlusion rate, Clinical class, Etiology, Anatomy, and Pathophysiology [CEAP] staging, and quality of life [QoL]) after the treatment of a GSV incompetence by saphenofemoral ligation and stripping (SFL/S) with endovenous laser ablation bare fiber, 980 nm (EVLA). METHODS: Patients with GSV insufficiency and varicose veins were randomized to either undergo SFL/S or EVLA, both of which were performed under tumescent anesthesia. The long-term results, which included the anatomic occlusion rate, varicose vein recurrence at the saphenofemoral junction (SFJ), relief of venous symptoms and QoL, were compared up to 5 years after treatment. RESULTS: A total of 130 legs of 121 patients were treated with either SFL/S (n = 68) or EVLA (n = 62). In the first 12 months, three recanalizations of the GSV were observed after EVLA. Up to 5 years later, more recurrent varicose veins caused by neoreflux in incompetent tributaries of the SFJ were observed in after EVLA (31%; 19/61) compared with SFL/S (7%; 4/60; P < .01). Neovascularization in the groin with clinically visible recurrence identified at 3 and 5 years post-treatment follow-up was only observed in the SFL/S group (n = 6). After 5 years, clinically visible recurrences originating from the SFJ region after EVLA were observed 33% (20/61) compared with 17% of patients (10/60) after SFL/S (P < .04). In both treatment groups, venous symptoms improved significantly. Patients in both groups reported a continuing significant cosmetic improvement measured on a visual analog scale of 1 to 10 (mean, 7.49; P < .01). There was no difference in the CEAP staging and a standardized, non-disease-specific instrument for describing and valuing health states (EuroQol-5D), between the groups up to 5 years after follow-up. CONCLUSIONS: At the 5-year follow-up, a significantly higher varicose vein recurrence rate originated at the SFJ region after EVLA compared with SFL/S. There were no differences in the relief of venous symptoms, CEAP staging, or general QoL between the groups.

The Propargyl Rearrangement to Functionalised Allyl-Boron and Borocation Compounds.

A diverse range of Lewis acidic alkyl, vinyl and aryl boranes and borenium compounds that are capable of new carbon-carbon bond formation through selective migratory group transfer have been synthesised. Utilising a series of heteroleptic boranes [PhB(C6 F5 )2 (1), PhCH2 CH2 B(C6 F5 )2 (2), and E-B(C6 F5 )2 (C6 F5 )C=C(I)R (R=Ph 3 a, nBu 3 b)] and borenium cations [phenylquinolatoborenium cation ([QOBPh][AlCl4 ], 4)], it has been shown that these boron-based compounds are capable of producing novel allyl- boron and boronium compounds through complex rearrangement reactions with various propargyl esters and carbamates. These reactions yield highly functionalised, synthetically useful boron substituted organic compounds with substantial molecular complexity in a one-pot reaction.

Contrasting Frustrated Lewis Pair Reactivity with Selenium- and Boron-Based Lewis Acids.

The activation of π-bonds in diynyl esters has been investigated by using soft and hard Lewis acids. In the case of the soft selenium Lewis acid PhSeCl, sequential activation of the alkyne bonds leads initially to an isocoumarin (1 equiv PhSeCl) and then to a tetracyclic conjugated structure with the isocoumarin subunit fused to a benzoselenopyran (3 equiv PhSeCl). Conversely, the reaction with the hard Lewis acidic borane B(C6 F5 )3 initiates a cascade reaction to yield a complex π-conjugated system containing phthalide and indene subunits.

Delivery of electroconvulsive therapy in Canada: a first national survey report on usage, treatment practice, and facilities.

OBJECTIVES: The aims of this study were to document electroconvulsive therapy use in Canada with respect to treatment facilities and caseloads based on a survey of practice (Canadian Electroconvulsive Therapy Survey/Enquete Canadienne Sur Les Electrochocs-CANECTS/ECANEC) and to consider these findings in the context of guideline recommendations. METHOD: All 1273 registered hospitals in Canada were contacted, and 175 sites were identified as providing electroconvulsive therapy; these sites were invited to complete a comprehensive questionnaire. The survey period was calendar year 2006 or fiscal year 2006/2007. National usage rates were estimated from the responses. RESULTS: Sixty-one percent of the sites completed the questionnaire; a further 10% provided caseload data. Seventy were identified as general; 31, as university teaching; and 21, as provincial psychiatric/other single specialty (psychiatric) hospitals. Caseload volumes ranged from a mean of fewer than 2 to greater than 30 treatments per week. Estimated national usage during the 1-year survey period was 7340 to 8083 patients (2.32-2.56 per 10,000 population) and 66,791 to 67,424 treatments (2.11-2.13 per 1000 population). The diagnostic indications, admission status, and protocols for course end points are described. CONCLUSIONS: The usage rates are in keeping with earlier Canadian data and with those from other jurisdictions. The difficulty obtaining caseload data from individual hospitals is indicative of the need for standardized data collection to support both clinical research and quality assurance. The wide variation in protocols for number of treatments per course indicates a need for better informed clinical guidelines. The broad range of caseload volumes suggests the need to review the economies of scale in the field.

Formation of C(sp(2))-boronate esters by borylative cyclization of alkynes using BCl3.

BCl3 is an inexpensive electrophile which induces the borylative cyclization of a wide range of substituted alkynes to regioselectively form polycycles containing synthetically versatile C(sp(2) )boronate esters. It proceeds rapidly, with good yields and is compatible with a range of functional groups and substitution patterns. Intermolecular 1,2-carboboration of alkynes is also achieved using BCl3 to generate trisubstituted vinyl boronate esters.

Recent developments linking retroviruses to human breast cancer: infectious agent, enemy within or both?

Evidence is accumulating that one or more beta-retrovirus is associated with human breast cancer. Retroviruses can exist as an infectious (exogenous) virus or as a part of the genetic information of cells due to germline integration (endogenous). An exogenous virus with a genome that is highly homologous to mouse mammary tumour virus is gaining acceptance as possibly being associated with human breast cancer, and recently furnished evidence is discussed in this article, as is the evidence for involvement of an endogenous human beta-retrovirus, HERV-K. Modes of interaction are also reviewed and linkages to the APOBEC3 family are suggested.

Mechanistic studies into amine-mediated electrophilic arene borylation and its application in MIDA boronate synthesis.

Direct electrophilic borylation using Y(2)BCl (Y(2) = Cl(2) or o-catecholato) with equimolar AlCl(3) and a tertiary amine has been applied to a wide range of arenes and heteroarenes. In situ functionalization of the ArBCl(2) products is possible with TMS(2)MIDA, to afford bench-stable and easily isolable MIDA-boronates in moderate to good yields. According to a combined experimental and computational study, the borylation of activated arenes at 20 °C proceeds through an S(E)Ar mechanism with borenium cations, [Y(2)B(amine)](+), the key electrophiles. For catecholato-borocations, two amine dependent reaction pathways were identified: (i) With [CatB(NEt(3))](+), an additional base is necessary to accomplish rapid borylation by deprotonation of the borylated arenium cation (σ complex), which otherwise would rather decompose to the starting materials than liberate the free amine to effect deprotonation. Apart from amines, the additional base may also be the arene itself when it is sufficiently basic (e.g., N-Me-indole). (ii) When the amine component of the borocation is less nucleophilic (e.g., 2,6-lutidine), no additional base is required due to more facile amine dissociation from the boron center in the borylated arenium cation intermediate. Borenium cations do not borylate poorly activated arenes (e.g., toluene) even at high temperatures; instead, the key electrophile in this case involves the product from interaction of AlCl(3) with Y(2)BCl. When an extremely bulky amine is used, borylation again does not proceed via a borenium cation; instead, a number of mechanisms are feasible including via a boron electrophile generated by coordination of AlCl(3) to Y(2)BCl, or by initial (heteroarene)AlCl(3) adduct formation followed by deprotonation and transmetalation.

Human papillomavirus and Epstein Barr virus in prostate cancer: Koilocytes indicate potential oncogenic influences of human papillomavirus in prostate cancer.

INTRODUCTION: The purpose of this study is to determine if high risk human papillomaviruses (HPV) and Epstein Barr virus (EBV) are both present in the same prostate cancer specimens. METHODS: We used a range of analytical techniques including in situ polymerase chain reaction (IS-PCR) and standard liquid PCR followed by sequencing of the product to seek to identify HPV and EBV in normal, benign, and malignant prostate tissues. RESULTS: Both HPV type 18 and EBV gene sequences were identified in a high and approximately equal proportion of normal, benign, and prostate cancer specimens. These sequences were located in the nuclei of prostate epithelial cells. HPV associated koilocytes were identified in 24% of prostate cancer specimens. CONCLUSIONS: The presence of both HPV and EBV gene sequences in most of the same normal, benign, and malignant prostate specimens is particularly noteworthy because of recent experimental evidence demonstrating that EBV and HPV can collaborate to increase proliferation of cultured cervical cells. Because the presence of EBV and HPV in normal, benign, and malignant prostate tissues appears to be ubiquitous, it is possible that they are harmless. On the other hand HPV type 18 in particular, has high oncogenic potential and may be associated with some prostate cancers. The identification of HPV associated koilocytes in prostate cancer specimens is an indication of HPV infection and potential oncogenic influences of human papillomavirus in prostate cancer.

Electroconvulsive therapy teaching in Canada: cause for concern.

AIM: The objective of this study was to present survey data on the teaching of electroconvulsive therapy (ECT) in health care centers across Canada. METHODS: Of 1273 centers identified, 175 were found to practice ECT. These centers were asked to complete a questionnaire, and 107 (61%) of them answered 5 questions dealing specifically with ECT teaching. These questions were as follows: (1) Does your facility have an ECT teaching program for residents in psychiatry? (2) How is ECT taught to residents in psychiatry? (3) If direct supervision of the administration of ECT is a requirement of the psychiatry training program, is there a minimum number of supervised treatments or minimum duration of training period? (4) Do residents provide unsupervised ECT at your center? (5) Which other groups of learners, if any, are provided with orientation, teaching, or training in ECT? RESULTS: Sixty percent of respondents had no ECT teaching program for psychiatry residents. Pedagogical methods varied, ranging from direct observation of ECT treatments to directed readings. Few centers required a minimum number of supervised treatments. No resident-administered ECT is performed without direct supervision. Interestingly, various groups of health care professionals were often invited to participate in ECT training. CONCLUSIONS: The situation regarding ECT teaching continues to be a cause for concern given the noted absence of organized, structured, and mandatory programs. No resident administering ECT, however, goes unsupervised, which is in keeping with good practice. Electroconvulsive therapy is taught in many different ways, and teaching is accessible to different groups of health care professionals. However, much remains to be done to standardize ECT teaching to render this therapy available to all those who need it and to overcome the stigma and bias associated with it.

Delivery of electroconvulsive therapy in Canada: a first national survey report on devices and technique.

OBJECTIVE: Electroconvulsive therapy (ECT) is an effective treatment for mood and other psychiatric disorders. Despite widespread use, the specifics of ECT practice in Canada are largely unknown. A nationwide survey designed to document current delivery was therefore conducted. METHOD: One hundred seventy-five Canadian ECT delivery sites were identified. A detailed questionnaire (13 pages, 76 questions grouped in 11 subheadings) was developed, translated into French, piloted, and then forwarded to all ECT centers. RESULTS: Return rate for the full questionnaire was 61%. Wide-ranging information pertaining to ECT was gathered. This article, which addresses the data specifically pertaining to ECT devices, electrical stimulus parameters and electrode placements, showed that many core aspects of ECT practice in Canada are in keeping with current recommendations. The use of old sine wave devices is virtually nonexistent. Electroencephalographic (EEG) monitoring of seizures is widespread. CONCLUSIONS: Specific concerns were identified, including the need for access to back-up devices at all centers, the lack of ECT credentialing requirements by Canadian hospitals, and a striking variation in dosing practices. An audit of Canadian practice and the development of a National Standards Document would be an essential next undertaking.

Descriptive epidemiology of upper respiratory disease and associated risk factors in cats in an animal shelter in coastal western Canada.

We examined 250 cats at an animal shelter in the coastal temperate region of Canada to determine whether age, source, gender, and sterilization status influenced risk of shedding at intake, transmission of infection, and development of clinical upper respiratory disease (URD). On admission, 28% of the cats were positive for 1 or more infectious agent related to URD; 21% were carriers of Mycoplasma felis and < 3% were carriers of feline calicivirus (FCV), feline herpesvirus-1 (FHV-1) or Bordetella bronchiseptica. Chlamydophila felis and H1N1 influenza virus were not detected. Carrier status was not affected by source, gender, sterilization status, or age (P > 0.05). Viral and bacterial shedding increased by 9% and 11%, respectively, over 3 sampling times (days 1, 4, and 10). Over 40 days after admission, the cumulative probability of developing URD was 2.2 times greater for stray than owner-surrendered cats (P = 0.02) and 0.5 times as great for neutered cats as for intact cats (P = 0.03). Cats that were shedding at intake were 2.6 times more likely to develop URD than were non-carriers (P < 0.002). Cats with FHV-1 and B. bronchiseptica infections were most at risk compared with non-shedding cats (P < 0.01).

Épidémiologie descriptive de la maladie respiratoire supérieure et facteurs de risque chez le chat dans un refuge situé dans la côte ouest du Canada. Nous avons examiné 250 chats dans un refuge de la région côtière tempérée du Canada. Nous avons déterminé la présence d'infection latente chez les chats de provenance diverses, par âge, par sexe (castré ou non-castré) lors de leur arrivé au refuge. Nous avons aussi étudié la transmission des pathogènes et le développement de symptômes rhinosinusites pendant leur séjour (40 jours). Au prélèvement du premier écouvillonnage, 21 % était positif pour le Mycoplasme felis (M. Felis) et moins de 3 % était positif pour le calicivirus félin (FCV), l'herpèsvirus félin de type 1 (FHV1) ou le Bordetella bronchiseptica. Ni Chlamydophila felis (C. felis) ni H1N1 n'ont été dépisté. Le nombre de porteurs latents n'était pas affecté par l'origine des chats, le sexe ou l'âge (P > 0,05). La probabilité cumulée de développer des symptômes de maladie était 2,64 fois supérieure pour les porteurs latents que pour les non-porteurs (P < 0,002); 2,21 fois supérieure pour les chats errants que pour les chats de maison (P = 0,02) et 0,5 fois supérieure pour les chats castrés que pour les chats non castré (P = 0,03). En particulier, les porteurs de FHV1 et B. bronchiseptica étaient plus à risque que les chats non-porteurs (P < 0,01). Nous avons conclu que les chats avec une infection latente de FHV1 ou B. Bronchiseptica, les chats errants et les chats castrés étaient plus vulnérables a la maladie des voies respiratoires supérieures dans ce refuge.(Traduit par les auteurs).

Haloboration of internal alkynes with boronium and borenium cations as a route to tetrasubstituted alkenes.

Hail boration! 2-Dimethylaminopyridine-ligated dihaloborocations [X2B(2-DMAP)](+) with a strained four-membered boracycle were used for the haloboration of terminal and dialkyl internal alkynes (see scheme). Esterification then provided vinyl boronate esters as useful precursors to tetrasubstituted alkenes. Following mechanistic studies, the scope of the haloboration was expanded simply by variation of the amine. Pin = 2,3-dimethyl-2,3-butanedioxy.