The SWADE model for landslide dating in time series of optical satellite imagery

Landslides are destructive natural hazards that cause substantial loss of life and impact on natural and built environments. Landslide frequencies are important inputs for hazard assessments. However, dating landslides in remote areas is often challenging. We propose a novel landslide dating technique based on Segmented WAvelet-DEnoising and stepwise linear fitting (SWADE), using the Landsat archive (1985–2017). SWADE employs the principle that vegetation is often removed by landsliding in vegetated areas, causing a temporal decrease in normalized difference vegetation index (NDVI). The applicability of SWADE and two previously published methods for landslide dating, harmonic modelling and LandTrendr, are evaluated using 66 known landslides in the Buckinghorse River area, northeastern British Columbia, Canada. SWADE identifies sudden changes of NDVI values in the time series and this may result in one or more probable landslide occurrence dates. The most-probable date range identified by SWADE detects 52% of the landslides within a maximum error of 1 year, and 62% of the landslides within a maximum error of 2 years. Comparatively, these numbers increase to 68% and 80% when including the two most-probable landslide date ranges, respectively. Harmonic modelling detects 79% of the landslides with a maximum error of 1 year, and 82% of the landslides with a maximum error of 2 years, but requires expert judgement and a well-developed seasonal vegetation cycle in contrast to SWADE. LandTrendr, originally developed for mapping deforestation, only detects 42% of landslides within a maximum error of 2 years. SWADE provides a promising fully automatic method for landslide dating, which can contribute to constructing landslide frequency-magnitude distributions in remote areas

Pyruvate Dehydrogenase Kinase Inhibition by Dichloroacetate in Melanoma Cells Unveils Metabolic Vulnerabilities

Melanoma is characterized by high glucose uptake, partially mediated through elevated pyruvate dehydrogenase kinase (PDK), making PDK a potential treatment target in melanoma. We aimed to reduce glucose uptake in melanoma cell lines through PDK inhibitors dichloroacetate (DCA) and AZD7545 and through PDK knockdown, to inhibit cell growth and potentially unveil metabolic co-vulnerabilities resulting from PDK inhibition. MeWo cells were most sensitive to DCA, while SK-MEL-2 was the least sensitive, with IC50 values ranging from 13.3 to 27.0 mM. DCA strongly reduced PDH phosphorylation and increased the oxygen consumption rate:extracellular acidification rate (OCR:ECAR) ratio up to 6-fold. Knockdown of single PDK isoforms had similar effects on PDH phosphorylation and OCR:ECAR ratio as DCA but did not influence sensitivity to DCA. Growth inhibition by DCA was synergistic with the glutaminase inhibitor CB-839 (2-to 5-fold sensitization) and with diclofenac, known to inhibit monocarboxylate transporters (MCTs) (3-to 8-fold sensitization). CB-839 did not affect the OCR:ECAR response to DCA, whereas diclofenac strongly inhibited ECAR and further increased the OCR:ECAR ratio. We conclude that in melanoma cell lines, DCA reduces proliferation through reprogramming of cellular metabolism and synergizes with other metabolically targeted drugs

Testicular cancer: Determinants of cisplatin sensitivity and novel therapeutic opportunities:Determinants of cisplatin sensitivity and novel therapeutic opportunities

Testicular cancer (TC) is the most common solid tumor among men aged between 15 and 40 years. TCs are highly aneuploid and the 12p isochromosome is the most frequent chromosomal abnormality. The mutation rate is of TC is low, with recurrent mutations in  KIT and  KRAS observed only at low frequency in seminomas. Overall cure rates are high, even in a metastatic setting, resulting from excellent cisplatin sensitivity of TCs. Factors contributing to the observed cisplatin sensitivity include defective DNA damage repair and a hypersensitive apoptotic response to DNA damage. Nonetheless, around 10–20% of TC patients with metastatic disease cannot be cured by cisplatin-based chemotherapy. Resistance mechanisms include downregulation of OCT4 and failure to induce PUMA and NOXA, elevated levels of MDM2, and hyperactivity of the PI3K/AKT/mTOR pathway. Several pre-clinical approaches have proven successful in overcoming cisplatin resistance, including specific targeting of PARP, MDM2 or AKT/mTOR combined with cisplatin. Finally, patient-derived xenograft models hold potential for mechanistic studies and pre-clinical validation of novel therapeutic strategies in TC. While clinical trials investigating targeted drugs have been disappointing, pre-clinical successes with chemotherapy and targeted drug combinations fuel the need for further investigation in clinical setting

Managing Load to Optimize Well-Being and Recovery During Short-Term Match Congestion in Elite Basketball

In elite basketball, players are exposed to intensified competition periods when participating in both national and international competitions. How coaches manage training between matches and in reference to match scheduling for a full season is not yet known. PURPOSE: First, to compare load during short-term match congestion (ie, ≥2-match weeks) with regular competition (ie, 1-match weeks) in elite male professional basketball players. Second, to determine changes in well-being, recovery, neuromuscular performance, and injuries and illnesses between short-term match congestion and regular competition. METHODS: Sixteen basketball players (age 24.8 [2.0] y, height 195.8 [7.5] cm, weight 94.8 [14.0] kg, body fat 11.9% [5.0%], VO2max 51.9 [5.3] mL·kg-1·min-1) were monitored during a full season. Session rating of perceived exertion (s-RPE) was obtained, and load was calculated (s-RPE × duration) for each training session or match. Perceived well-being (fatigue, sleep quality, general muscle soreness, stress levels, and mood) and total quality of recovery were assessed each training day. Countermovement jump height was measured, and a list of injuries and illnesses was collected weekly using the adapted Oslo Sports Trauma Research Center Questionnaire on Health Problems. RESULTS: Total load (training sessions and matches; P < .001) and training load (P < .001) were significantly lower for ≥2-match weeks. Significantly higher well-being (P = .01) and less fatigue (P = .001) were found during ≥2-match weeks compared with 1-match weeks. CONCLUSION: Total load and training load were lower during short-term match congestion compared with regular competition. Furthermore, better well-being and less fatigue were demonstrated within short-term match congestion. This might indicate that coaches tend to overcompensate training load in intensified competition

Evaluating pellet and meal feeding regimens on finishing pig performance, stomach morphology, and carcass characteristics

Citation: De Jong, J. A., DeRouchey, J. M., Tokach, M. D., Dritz, S. S., Goodband, R. D., Woodworth, J. C., & Allerson, M. W. (2016). Evaluating pellet and meal feeding regimens on finishing pig performance, stomach morphology, and carcass characteristics. Journal of Animal Science, 94(11), 4781-4788. doi:10.2527/jas2016-0461A total of 2,100 pigs (PIC 327 x 1050; initially 31.2 kg BW) were used in a 118-d trial to determine the effects of pellet or meal feeding regimens on finishing pig growth performance, stomach morphology, and carcass characteristics. Pens of pigs were balanced by initial BW and randomly allotted to 1 of 6 dietary treatments (14 pens/treatment with 25 pigs/pen). Pens were sorted by gender allowing for 7 barrow pens and 7 gilt pens per treatment. The same corn-soybean meal-based diets containing 15% dried distillers' grains with solubles were used for all treatments and fed in 5 phases. Phases were fed from d 0 to 28, 28 to 56, 56 to 84, 84 to 98, and 98 to 118. The 6 treatments included a meal or pelleted diet fed from d 0 to 118, a meal diet fed from d 0 to 70 followed by pellets from d 70 to 118, a pelleted diet fed from d 0 to 70 followed by a meal diet from d 70 to 118, or pellets and meal rotated every 2 wk starting with meal or pellets. On d 110, 4 pigs from each pen were harvested and stomachs collected, from which a combined ulcer and keratinization score was determined for each pig. Overall, there were no differences in ADG across feeding regimens. Pigs fed meal throughout had the greatest (P < 0.05) ADFI, whereas pigs fed pellets throughout had the lowest (P < 0.05), with all other treatments intermediate (P < 0.05). Pigs fed pelleted diets throughout had the greatest (P < 0.05) G: F, whereas pigs fed meal throughout had the worst G: F (P < 0.05), with all other treatments intermediate (P < 0.05). When pelleted diets were fed for the last 58 d or for the entire trial, the incidence of ulceration and keratinization increased (P < 0.05), whereas pigs fed meal for the last 58 d had a lower incidence (P < 0.05), with all other treatments intermediate (P < 0.05). Feeding pellets throughout increased (P < 0.05) the number of pigs removed per pen compared with all other treatments. Pig removals were determined by an on-site farm manager when pigs were at risk due to weight loss, health, or animal welfare concerns and needed to be separated from the general population. There were no differences for any carcass characteristics measured including HCW, carcass yield, backfat depth, loin depth, and percentage lean. In conclusion, feeding pelleted diets improved G: F but increased stomach ulceration and pig removals; however, rotating pellets and meal diets provided an intermediate G: F response and moderated stomach ulcerations compared with feeding only pellets

Among B cell non-Hodgkin's lymphomas, MALT lymphomas express a unique antibody repertoire with frequent rheumatoid factor reactivity

We analyzed the structure of antigen receptors of a comprehensive panel of mature B non-Hodgkin's lymphomas (B-NHLs) by comparing, at the amino acid level, their immunoglobulin (Ig)VH-CDR3s with CDR3 sequences present in GenBank. Follicular lymphomas, diffuse large B cell lymphomas, Burkitt's lymphomas, and myelomas expressed a CDR3 repertoire comparable to that of normal B cells. Mantle cell lymphomas and B cell chronic lymphocytic leukemias (B-CLLs) expressed clearly restricted albeit different CDR3 repertoires. Lymphomas of mucosa-associated lymphoid tissues (MALTs) were unique as 8 out of 45 (18%) of gastric- and 13 out of 32 (41%) of salivary gland-MALT lymphomas expressed B cell antigen receptors with strong CDR3 homology to rheumatoid factors (RFs). Of note, the RF-CDR3 homology without exception included N-region–encoded residues in the hypermutated IgVH genes, indicating that they were stringently selected for reactivity with auto-IgG. By in vitro binding studies with 10 MALT lymphoma–derived antibodies, we showed that seven of these cases, of which four with RF-CDR3 homology, indeed possessed strong RF reactivity. Of one MALT lymphoma, functional proof for selection of subclones with high RF affinity was obtained. Interestingly, RF-CDR3 homology and t(11;18) appeared to be mutually exclusive features and RF-CDR3 homology was not encountered in any of the 19 pulmonary MALT lymphomas studied

Effects of increasing dietary wheat middlings on nursery pig performance from 15 to 50 lb

A total of 210 pigs (PIC 327 × 1050, initially 15.12 lb BW) were used in a 35-d trial to evaluate the effects of increasing dietary wheat middlings (midds) on growth performance of 15- to 50-lb nursery pigs. Pens of pigs were balanced by initial BW and randomly allotted to 1 of 5 dietary treatments with 6 replications per treatment. The 5 corn-soybean meal–based diets contained 0, 5, 10, 15, or 20% midds. Pigs were fed in a 2-phase feeding program from d 0 to 14 and d 14 to 35. Diets were not balanced for energy; thus, as midds increased, dietary energy concentrations decreased. From d 0 to 14, midds had no effect on growth performance; however, from d 14 to 35, pigs fed increasing midds had decreased ADG (linear, P \u3c 0.02) and poorer F/G (linear, P \u3c 0 .004). Furthermore, pigs fed increasing midds had lower (linear, P \u3c 0.05) feed cost/pig, revenue/pig, and income over feed cost (IOFC), and a tendency for increased (quadratic, P \u3c 0.07) feed cost/lb gain. Overall (d 0 to 35), increasing dietary midds worsened F/G (quadratic, P \u3c 0.01), driven by poorer F/G for pigs fed 15 and 20% midds. We also observed a quadratic effect (P \u3c 0.004) for feed cost/lb gain, with inclusion rates of 0 and 20% having the highest value. Caloric efficiency responded in a quadratic manner (P \u3c 0.01) on both an ME and NE basis with improved caloric effi¬ciencies at intermediate levels (mainly 5%) of dietary middlings compared with 0 and 20% inclusions. These data suggest that the inclusion of midds at levels up to 15% do not negatively affect performance in 15- to 50-lb nursery pigs. Although we observed a linear decrease in overall IOFC, both inclusion rates of 5 and 10% were numerically more profitable than the control.; Swine Day, Manhattan, KS, November 15, 201

Adrenocorticotropic hormone elicits gonadotropin secretion in premenopausal women

STUDY QUESTION Does adrenocorticotropic hormone (ACTH) induce gonadotropin release in premenopausal women? SUMMARY ANSWER Administration of ACTH stimulates gonadotropin release, most likely by stimulation of the production of cortisol, in premenopausal women. WHAT IS KNOWN ALREADY In animal models, acute activation of the hypothalamic-pituitary-adrenal (HPA) axis has been shown to induce gonadotropin release in the presence of sufficiently high estrogen levels. However, it is unknown whether the HPA axis has a similar influence on gonadotropin release in humans. STUDY DESIGN, SIZE, DURATION This study had a mixed factorial design. A total of 60 healthy female participants participated in the experimental study. PARTICIPANTS/MATERIALS, SETTING, METHODS The study sample comprised three distinct hormonal-based populations according to their levels of progesterone (PROG) and estradiol (E2): (i) low-PROG-low-E2, (ii) low-PROG-high-E2 and (iii) high-PROG-high-E2 women. A low dose (1 μg) of ACTH was administered to all study participants. Serum steroid and gonadotropin concentrations were measured prior to, and at 30 and 90 minutes after, intravenous ACTH administration. MAIN RESULTS AND THE ROLE OF CHANCE Mean serum cortisol levels increased significantly following ACTH administration in all groups (P < 0.001). Similarly, the serum levels of 17-OH-PROG, androstenedione, dehydroepiandrosterone and testosterone increased significantly in all groups (P < 0.01). The low-PROG-high-E2 and high-PROG-high-E2 groups exhibited a significant increase in LH and FSH levels (P < 0.001), whereas the low-PROG-low-E2 group demonstrated blunted LH and FSH responses to ACTH administration (P < 0.05). LIMITATIONS, REASONS FOR CAUTION Testing was performed during the lut

A manual-based individual therapy to improve metacognition in schizophrenia:protocol of a multi-center RCT

BACKGROUND: Metacognitive dysfunction has been widely recognized as a feature of schizophrenia. As it is linked with deficits in several aspects of daily life functioning, improvement of metacognition may lead to improvement in functioning. Individual psychotherapy might be a useful form of treatment to improve metacognition in patients with schizophrenia; multiple case reports and a pilot study show promising results. The present study aims to measure the effectiveness of an individual, manual-based therapy (Metacognitive Reflection and Insight Therapy, MERIT) in improving metacognition in patients with schizophrenia. We also want to examine if improvement in metacognitive abilities is correlated with improvements in aspects of daily life functioning namely social functioning, experience of symptoms, quality of life, depression, work readiness, insight and experience of stigma. METHODS/DESIGN: MERIT is currently evaluated in a multicenter randomized controlled trial. Thirteen therapists in six mental health institutions in the Netherlands participate in this study. Patients are randomly assigned to either MERIT or the control condition: treatment as usual (TAU). DISCUSSION: If proven effective, MERIT can be a useful addition to the care for schizophrenia patients. The design brings along some methodological difficulties, these issues are addressed in the discussion of this paper. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN16659871

Differential hormone-dependent transcriptional activation and -repression by naturally occurring human glucocorticoid receptor variants

The molecular mechanisms underlying primary glucocorticoid resistance or hypersensitivity are not well understood. Using transfected COS-1 cells as a model system, we studied gene regulation by naturally occurring mutants of the glucocorticoid receptor (GR) with single-point mutations in the regions encoding the ligand-binding domain or the N-terminal domain reflecting different phenotypic expression. We analyzed the capacity of these GR variants to regulate transcription from different promoters, either by binding directly to positive or negative glucocorticoid-response elements on the DNA or by interfering with protein-protein interactions. Decreased dexamethasone (DEX) binding to GR variants carrying mutations in the ligand-binding domain correlated well with decreased capacity to activate transcription from the mouse mammary tumor virus (MMTV) promoter. One variant, D641V, which suboptimally activated MMTV promoter-mediated transcription, repressed a PRL promoter element containing a negative glucocorticoid-response element with wild type activity. DEX-induced repression of transcription from elements of the intercellular adhesion molecule-1 promoter via nuclear factor-kappaB by the D641V variant was even more efficient compared with the wild type GR. We observed a general DEX-responsive AP-1-mediated transcriptional repression of the collagenase-1 promoter, even when receptor variants did not activate transcription from the MMTV promoter. Our findings indicate that different point mutations in the GR can affect separate pathways of gene regulation in a differential fashion, which can explain the various phenotypes observed