Rethinking False Spring Risk

Temperate plants are at risk of being exposed to late spring freezes. These freeze events - often called false springs - are one of the strongest factors determining temperate plants species range limits and can impose high ecological and economic damage. As climate change may alter the prevalence and severity of false springs, our ability to forecast such events has become more critical, and it has led to a growing body of research. Many false spring studies largely simplify the myriad complexities involved in assessing false spring risks and damage. While these studies have helped advance the field and may provide useful estimates at large scales, studies at the individual to community levels must integrate more complexity for accurate predictions of plant damage from late spring freezes. Here we review current metrics of false spring, and how, when and where plants are most at risk of freeze damage. We highlight how life stage, functional group, species differences in morphology and phenology, and regional climatic differences contribute to the damage potential of false springs. More studies aimed at understanding relationships among species tolerance and avoidance strategies, climatic regimes, and the environmental cues that underlie spring phenology would improve predictions at all biological levels. An integrated approach to assessing past and future spring freeze damage would provide novel insights into fundamental plant biology, and offer more robust predictions as climate change progresses, which is essential for mitigating the adverse ecological and economic effects of false springs

Combination therapy with rituximab, low-dose cyclophosphamide, and prednisone for idiopathic membranous nephropathy: a case series

BACKGROUND: Membranous nephropathy is a common cause of the nephrotic syndrome. Treatment with standard regimens fails to induce complete remission in most patients. We evaluated the efficacy of combination therapy with rituximab, low-dose, oral cyclophosphamide, and an accelerated prednisone taper (RCP) for the treatment of idiopathic membranous nephropathy. METHODS: We analyzed 15 consecutive patients with idiopathic membranous nephropathy treated with RCP at Massachusetts General Hospital. Seven patients (47%) received RCP as initial therapy, and the other eight patients (53%) received RCP for relapsing or refractory disease. All patients had at least 1 year of follow-up. The co-primary outcomes were attainment of partial and complete remission. Partial remission was defined as a urinary protein to creatinine ratio (UPCR) < 3 g/g and a 50% reduction from baseline. Complete remission was defined as a UPCR < 0.3 g/g. Secondary outcomes were serious adverse events and the change in proteinuria, serum creatinine, serum albumin, cholesterol, triglycerides, and immunoglobulin G levels after 1 year of treatment. RESULTS: Over a median follow-up time of 37 (IQR, 34-44) months, 100% of patients achieved partial remission and 93% of patients achieved complete remission at a median time of 2 and 13 months, respectively. After 1 year of treatment, median (IQR) UPCR declined from 8.2 (6.6-11.1) to 0.3 (0.2-0.7) g/g (P < 0.001). Three serious adverse events occurred over 51 patient years. No patients died or progressed to ESKD. CONCLUSIONS: Treatment of idiopathic membranous nephropathy with RCP resulted in high rates of complete remission. Larger studies evaluating this regimen are warranted

Human influence on growing-period frosts like the early April 2021 in Central France

International audienceAbstract. In early April 2021 several days of harsh frost affected central Europe. This led to very severe damage in grapevine and fruit trees in France, in regions where young leaves had already unfolded due to unusually warm temperatures in the preceding month (March 2021). We analysed with observations and 172 climate model simulations how human-induced climate change affected this event over central France, where many vineyards are located. We found that, without human-caused climate change, such temperatures in April or later in spring would have been even lower by 1.2 ∘C (0.75 to 1.7 ∘C). However, climate change also caused an earlier occurrence of bud burst that we characterized in this study by a growing degree day index value. This shift leaves young leaves exposed to more winter-like conditions with lower minimum temperatures and longer nights, an effect that overcompensates the warming effect. Extreme cold temperatures occurring after the start of the growing season such as those of April 2021 are now 2 ∘C colder (0.5 to 3.3 ∘C) than in preindustrial conditions, according to observations. This observed intensification of growing-period frosts is attributable, at least in part, to human-caused climate change with each of the five climate model ensembles used here simulating a cooling of growing-period annual temperature minima of 0.41 ∘C (0.22 to 0.60 ∘C) since preindustrial conditions. The 2021 growing-period frost event has become 50 % more likely (10 %–110 %). Models accurately simulate the observed warming in extreme lowest spring temperatures but underestimate the observed trends in growing-period frost intensities, a fact that yet remains to be explained. Model ensembles all simulate a further intensification of yearly minimum temperatures occurring in the growing period for future decades and a significant probability increase for such events of about 30 % (20 %–40 %) in a climate with global warming of 2 ∘C

Cellphone-Based Hand-Held Microplate Reader for Point-of-Care Testing of Enzyme-Linked Immunosorbent Assays

Standard microplate based enzyme-linked immunosorbent assays (ELISA) are widely utilized for various nanomedicine, molecular sensing, and disease screening applications, and this multiwell plate batched analysis dramatically reduces diagnosis costs per patient compared to nonbatched or nonstandard tests. However, their use in resource-limited and field-settings is inhibited by the necessity for relatively large and expensive readout instruments. To mitigate this problem, we created a hand-held and cost-effective cellphone-based colorimetric microplate reader, which uses a 3D-printed optomechanical attachment to hold and illuminate a 96-well plate using a light-emitting-diode (LED) array. This LED light is transmitted through each well, and is then collected via 96 individual optical fibers. Captured images of this fiber-bundle are transmitted to our servers through a custom-designed app for processing using a machine learning algorithm, yielding diagnostic results, which are delivered to the user within ∼1 min per 96-well plate, and are visualized using the same app. We successfully tested this mobile platform in a clinical microbiology laboratory using FDA-approved mumps IgG, measles IgG, and herpes simplex virus IgG (HSV-1 and HSV-2) ELISA tests using a total of 567 and 571 patient samples for training and blind testing, respectively, and achieved an accuracy of 99.6%, 98.6%, 99.4%, and 99.4% for mumps, measles, HSV-1, and HSV-2 tests, respectively. This cost-effective and hand-held platform could assist health-care professionals to perform high-throughput disease screening or tracking of vaccination campaigns at the point-of-care, even in resource-poor and field-settings. Also, its intrinsic wireless connectivity can serve epidemiological studies, generating spatiotemporal maps of disease prevalence and immunity

L'utilisation par la viticulture française d'un exercice de prospective pour l'élaboration d'une stratégie d'adaptation au changement climatique

Foresight studies are regularly conducted at sectoral or geographical scales, in order to help policy makers and economic actors to define their strategy of adaptation to climate change (CC)

A retrospective analysis of clinical outcome of patients with chemo-refractory metastatic breast cancer treated in a single institution phase I unit

BACKGROUND AND METHODS: Novel approaches to treat chemo-refractory metastatic breast cancer (MBC) are currently under investigation. This retrospective series reviews the outcome of 70 MBC patients who have participated in 30 phase I trials at the Royal Marsden Hospital from 2002 to 2009. RESULTS: The median treatment lines before phase I trial entry for MBC was 5 (range: 1-12 lines). The overall response rate was 11.4% (95% CI: 4.0-18.9%) and the clinical benefit rate at 4 months was 20% (95% CI: 10.6-29.3). The median time to progression was 7.0 weeks (95% CI: 6.4-7.5) and median overall survival was 8.7 months (95% CI: 7.6-9.8) from start of first phase I treatment. No patients discontinued trial because of treatment-related toxicities. Abnormal lactate dehydrogenase, serum albumin <35 mg per 100 ml, >or=5 previous treatment lines, liver metastases and Eastern Cooperative Group performance status >or=2 at study entry were significantly associated with poor overall survival in multivariate analysis. CONCLUSION: This retrospective analysis provides evidence that patients with MBC tolerate phase I clinical trials and a significant proportion of patients with chemo-refractory disease, particularly those with triple-negative or Her2-positive breast cancer, may benefit from treatment

Dose Dependent Effects on Cell Cycle Checkpoints and DNA Repair by Bendamustine

Bendamustine (BDM) is an active chemotherapeutic agent approved in the U. S. for treating chronic lymphocytic leukemia and non-Hodgkin lymphoma. Its chemical structure suggests it may have alkylator and anti-metabolite activities; however the precise mechanism of action is not well understood. Here we report the concentration-dependent effects of BDM on cell cycle, DNA damage, checkpoint response and cell death in HeLa cells. Low concentrations of BDM transiently arrested cells in G2, while a 4-fold higher concentration arrested cells in S phase. DNA damage at 50, but not 200 µM, was efficiently repaired after 48 h treatment, suggesting a difference in DNA repair efficiency at the two concentrations. Indeed, perturbing base-excision repair sensitized cells to lower concentrations of BDM. Timelapse studies of the checkpoint response to BDM showed that inhibiting Chk1 caused both the S- and G2-arrested cells to prematurely enter mitosis. However, whereas the cells arrested in G2 (low dose BDM) entered mitosis, segregated their chromosomes and divided normally, the S-phase arrested cells (high dose BDM) exhibited a highly aberrant mitosis, whereby EM images showed highly fragmented chromosomes. The vast majority of these cells died without ever exiting mitosis. Inhibiting the Chk1-dependent DNA damage checkpoint accelerated the time of killing by BDM. Our studies suggest that BDM may affect different biological processes depending on drug concentration. Sensitizing cells to killing by BDM can be achieved by inhibiting base-excision repair or disrupting the DNA damage checkpoint pathway