Genetics of phenological development and implications for seed yield in lentil.

Understanding phenology, its genetics and agronomic consequences, is critical for crop adaptation. Here we aim at (1) characterising lentil response to photoperiod with a focus on five loci: the lentil ELF3 ortholog Sn, two loci linked to clusters of lentil FT orthologs and two loci without candidates in chromosomes 2 and 5 (exp. 1: 36 lines, short and long day in phytotron); (2) establishing phenology-yield relationship (exp. 2: 25 lines, 11 field environments). A vintage perspective, where we quantify time trends in phenotype over three decades of breeding, links both experiments. Yield increased linearly from older to newer varieties at 29 kg ha-1 yr-1 or 1.5% yr-1, correlated negatively with flowering time in both winter- and summer-rainfall regimes, and decoupled from biomass in favourable environments. Time to flowering shortened from older to newer varieties at -0.56 % yr-1 in the field, and -0.42 % yr-1 (short day) and -0.99 % yr-1 (long day) in the phytotron. Early-flowering lines of diverse origin carried multiple early alleles for the five loci, indicating that at least some of these loci affect phenology additively. Current germplasm primarily features the early flowering haplotype for an FTb cluster region, hence the potential to increase phenological diversity with yield implications.

Gliosarcoma with extensive extracranial metastatic spread and familial coincidence: A case report.

Gliosarcoma is a rare histopathological subtype of glioblastoma. Metastatic spreading is unusual. In this report, we illustrate a case of gliosarcoma with extensive extracranial metastases with confirmation of histological and molecular concordance between the primary tumor and a metastatic lesion of the lung. Only the autopsy revealed the extent of metastatic spread and the hematogenous pattern of metastatic dissemination. Moreover, the case bared a familial coincidence of malignant glial tumors as the patient's son was diagnosed with a high-grade glioma shortly after the patient's death. By molecular analysis (Sanger and next generation panel sequencing), we could confirm that both patient's tumors carried mutations in the TP53 gene. Interestingly, the detected mutations were located in different exons. Altogether, this case draws attention to the fact that sudden clinical aggravation could be caused by the rare phenomenon of metastatic spread and should therefore be always taken into consideration, even at an early disease stage. Furthermore, the presented case highlights the contemporary value of autoptic pathological examination.

Patterns, predictors and prognostic relevance of high-grade hematotoxicity after temozolomide or temozolomide-lomustine in the CeTeG/NOA-09 trial.

PURPOSE: In the randomized phase III trial CeTeG/NOA-09, temozolomide (TMZ)/lomustine (CCNU) combination therapy was superior to TMZ in newly diagnosed MGMT methylated glioblastoma, albeit reporting more frequent hematotoxicity. Here, we analyze high grade hematotoxicity and its prognostic relevance in the trial population. METHODS: Descriptive and comparative analysis of hematotoxicity adverse events ≥ grade 3 (HAE) according to the Common Terminology of Clinical Adverse Events, version 4.0 was performed. The association of HAE with survival was assessed in a landmark analysis. Logistic regression analysis was performed to predict HAE during the concomitant phase of chemotherapy. RESULTS: HAE occurred in 36.4% and 28.6% of patients under CCNU/TMZ and TMZ treatment, respectively. The median onset of the first HAE was during concomitant chemotherapy (i.e. first CCNU/TMZ course or daily TMZ therapy), and 42.9% of patients with HAE receiving further courses experienced repeat HAE. Median HAE duration was similar between treatment arms (CCNU/TMZ 11.5; TMZ 13 days). Chemotherapy was more often discontinued due to HAE in CCNU/TMZ than in TMZ (19.7 vs. 6.3%, p = 0.036). The occurrence of HAE was not associated with survival differences (p = 0.76). Regression analysis confirmed older age (OR 1.08) and female sex (OR 2.47), but not treatment arm, as predictors of HAE. CONCLUSION: Older age and female sex are associated with higher incidence of HAE. Although occurrence of HAE was not associated with shorter survival, reliable prediction of patients at risk might be beneficial to allow optimal management of therapy and allocation of supportive measures. TRIAL REGISTRATION: NCT01149109.

Promising functional outcomes following anterior cruciate ligament repair with suture augmentation.

PURPOSE: There has been a renewed interest in the repair of the torn anterior cruciate ligament (ACL). Purpose of this study was to evaluate the functional outcome of arthroscopic ACL repair with additional suture augmentation (SA), hypothesizing that isolated ACL ruptures would yield superior patient-reported outcome measures (PROMs) compared to those with concomitant meniscal and/or ligamentous injuries. METHODS: This is a retrospective analysis of 93 consecutive patients (67 female, median age 42 years) who underwent arthroscopic ACL repair with SA between January 2017 and March 2019 for an acute traumatic ACL tear confirmed by magnetic resonance imaging (MRI). Patients with pre- or intraoperative mid-substance or distal ACL tears and/or poor tissue quality of the ACL remnant were not considered for ACL repair but were scheduled for an ACL reconstruction with a tendon autograft. In patients who underwent ACL repair with SA, the SA construct was proximally stabilized with a flip-button and distally with a suture anchor. Surgery was preferably performed on the day of injury and all surgeries were performed by the same surgeon. Postoperative rehabilitation included partial weight-bearing (20 kg) for 6 weeks and immobilization in a brace limited at 90-degrees of knee flexion for 4 weeks. Patient-reported outcome measures (PROMs) were determined using International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form, Lysholm Score (LS), Tegner Activity Score (TS) and Forgotten Joint Score (FJS). Knee-laxity was assessed using the KT-1000 arthrometer (Med Metrics Corp. Inc., San Diego, USA). RESULTS: Nine patients underwent revision surgery for a traumatic re-tear (four patients) and chronic instability (five patients) and were excluded from further functional analysis. Functional results of 77 patients (54 female) with a median age of 44 years (IQR 33-51) on the day of surgery were available for follow-up after a median time of 35 months (IQR 33-44). Concomitant injuries were observed in 66 Patients (86%), meniscal injuries in 43 patients (55%) and ligamentous injuries in 50 patients (65%). Median interval from injury to surgery was 1 day (IQR 0-1) with 81% (62/77) of patients being treated within 24 h of injury. The median IKDC was 92 (IQR 86-99), the median LS was 95 (IQR 86-100), the median pre-traumatic TS was 7 (IQR 6-7), the median post-traumatic TS was 6 (IQR 5-7) with a non-significant median difference (TSDiff) of 0 (IQR 0-1). The median FJS was 95 (IQR 78-98). KT-1000 measurements were available in 34 of 77 patients with a median postoperative laxity compared to the uninjured side of 1 mm (IQR 0-2). Interval from injury to surgery, patients' age, body mass index (BMI), knee laxity and concomitant ligamentous or meniscal injuries had no statistically significant impact on postoperative PROMs (n.s.). CONCLUSION: Following arthroscopic ACL repair with SA good-to-excellent functional results were observed. However, a failure rate of 10% cannot be neglected and warrants further attention. Concomitant injuries to the meniscus and/or collateral ligaments do not seem to be associated with inferior PROMs. LEVEL OF EVIDENCE: Level IV.

Interfacial Engineering with a Nanoparticle-Decorated Porous Carbon Structure on ß″-Alumina Solid-State Electrolytes for Molten Sodium Batteries.

We present a novel anode interface modification on the ß″-alumina solid-state electrolyte that improves the wetting behavior of molten sodium in battery applications. Heat treating a simple slurry, composed only of water, acetone, carbon black, and lead acetate, formed a porous carbon network decorated with PbOx (0 ≤ x ≤ 2) nanoparticles between 10 and 50 nm. Extensive performance analysis, through impedance spectroscopy and symmetric cycling, shows a stable, low-resistance interface for close to 6000 cycles. Furthermore, an intermediate temperature Na-S cell with a modified ß″-alumina solid-state electrolyte could achieve an average stable cycling capacity as high as 509 mA h/g. This modification drastically decreases the amount of Pb content to approximately 3% in the anode interface (6 wt % or 0.4 mol %) and could further eliminate the need for toxic Pb altogether by replacing it with environmentally benign Sn. Overall, in situ reduction of oxide nanoparticles created a high-performance anode interface, further enabling large-scale applications of liquid metal anodes with solid-state electrolytes.

Ultrastructural analysis of explanted CyPass microstents and correlation with clinical findings.

PURPOSE: The purpose of this study was to obtain insight into cellular processes after CyPass microstent implantation into the supraciliary space. With this knowledge, we expected to find some reason for surgical failure. METHODS: Nine CyPass microstents of 8 patients with primary open-angle glaucoma (n = 1), pseudoexfoliation glaucoma (n = 5), uveitic glaucoma (n = 1), and posttraumatic open-angle glaucoma (n = 1) were explanted due to recurrence of IOP elevation, corneal decompensation, or persistent hypotony. The explants were processed for light and transmission electron microscopy. RESULTS: Fibrotic material, consisting of collagen fibrils, microfibrils, pseudoexfoliation fibrils produced by activated fibroblasts, was detected in the stent lumen of 4/5 pseudoexfoliation glaucoma patients and also in posttraumatic open-angle glaucoma. Fibrotic material was also present on the outer surface and within fenestrations of the majority of stents. Complete absence of fibrotic reaction was noticed in 3 of 9 microstents. CONCLUSION: Although MIGS is known to be less invasive than conventional surgery, implants placed in the suprachoroidal space may be adversely affected by a fibrotic tissue reaction resulting in implant failure. Understanding mechanisms and risk factors leading to fibrotic scarring following antiglaucomatous surgery may help to develop novel strategies that improve surgical outcome.

A retrospective audit of postoperative days alive and out of hospital, including before and after implementation of the WHO surgical safety checklist.

We implemented the World Health Organization surgical safety checklist at Auckland City Hospital from November 2007. We hypothesised that the checklist would reduce postoperative mortality and increase days alive and out of hospital, both measured to 90 postoperative days. We compared outcomes for cohorts who had surgery during 18-month periods before vs. after checklist implementation. We also analysed outcomes during 9 years that included these periods (July 2004-December 2013). We analysed 9475 patients in the 18-month period before the checklist and 10,589 afterwards. We analysed 57,577 patients who had surgery from 2004 to 2013. Mean number of days alive and out of hospital (95%CI) in the cohort after checklist implementation was 1.0 (0.4-1.6) days longer than in the cohort preceding implementation, p < 0.001. Ninety-day mortality was 395/9475 (4%) and 362/10,589 (3%) in the cohorts before and after checklist implementation, multivariable odds ratio (95%CI) 0.93 (0.80-1.09), p = 0.4. The cohort changes in these outcomes were indistinguishable from longer-term trends in mortality and days alive and out of hospital observed during 9 years, as determined by Bayesian changepoint analysis. Postoperative mortality to 90 days was 228/5686 (4.0%) for Maori and 2047/51,921 (3.9%) for non-Maori, multivariable odds ratio (95%CI) 0.85 (0.73-0.99), p = 0.04. Maori spent on average (95%CI) 1.1 (0.5-1.7) fewer days alive and out of hospital than non-Maori, p < 0.001. In conclusion, our patients experienced improving postoperative outcomes from 2004 to 2013, including the periods before and after implementation of the surgical checklist. Maori patients had worse outcomes than non-Maori.

Five-year cause-specific survival after meningioma surgery. A nationwide population-based study.

BACKGROUND: Survival after meningioma surgery is often reported with inadequate allowance for competing causes of death. METHODS: We processed the French administrative medical database (Système National des Données de Santé: SNDS), to retrieve appropriate cases of surgically treated meningioma. Cause-specific survival in meningioma-related death was analyzed with the Fine & Gray (F&G) and cause-specific (CS) Cox models to identify associated factors. RESULTS: Five-year cumulative incidence was 2.85% for meningioma-related death and 6.3% for unrelated death (P<0.001). In the adjusted F&G and cause-specific Cox regression models for meningioma-related death, gender, age at surgery, co-morbidities, neurofibromatosis type 2, tumor insertion, tumor grade, cerebrospinal fluid (CSF) shunt insertion, preoperative embolization and need for redo surgery for recurrence emerged as independent prognostic factors of cause-specific survival (CSS) in meningioma-related death. CONCLUSION: At 5 years, the risk of meningioma-unrelated death was 2.21-fold greater than the risk of dying from the meningioma disease. Five-year CSS after meningioma surgery was greater in younger adults with benign spinal meningioma with low comorbidity. Those with malignant cranial tumor requiring preoperative embolization or CSF shunting for associated hydrocephalus and with severely degraded overall health status showed a significantly increased risk of meningioma-related death. Redo surgery for recurrence failed to improve the risk of meningioma-related death. We recommend the use of net survival methods such as CSS in meningioma studies where unrelated mortality is predominant, as this approach results in more accurate estimates of disease risk and associated predictors.

Evaluation of owner medication adherence for canine cardiovascular disease in the referral setting.

OBJECTIVE: To evaluate owners' medication adherence for management of cardiovascular disease in the small animal specialty setting. ANIMALS, MATERIALS, AND METHODS: A questionnaire-based study of owners at a single, multispecialty, small animal referral center was conducted. Owners completed a written survey evaluating demographics, degree of medication adherence, and difficulties encountered for medication adherence. Owners were free to decline participation in the study. RESULTS: Ninety-six questionnaires were completed during the study period. Fifty-four respondents (56.3%) reported treating their pet for over one year for cardiovascular disease, and myxomatous mitral valve disease was the most common diagnosis (76.0%). Twenty-nine (30.2%) respondents felt they could consistently administer a maximum of three medications daily, and 46 (47.9%) respondents reported twice-daily dosing was the highest frequency of administration that could be consistently achieved. Twenty-two respondents (22.9%) reported that their pet required daily medications for at least one other chronic condition besides cardiac disease. Seventeen respondents (17.7%) reported at least occasionally missing medications, although only one (1.0%) reported it was more than 20% of medications per week. CONCLUSIONS: Medication adherence was high in this study population. Almost one-half of owners surveyed reported being unable to consistently administer more than three medications daily, and approximately one-quarter of patients were treated for at least one additional chronic condition requiring daily medications, in addition to cardiac disease. Clinicians should be aware of these factors when determining optimal treatment protocols for the management of cardiovascular disease in dogs.

Recent Progress in Cathode Materials for Sodium-Metal Halide Batteries.

Transitioning from fossil fuels to renewable energy sources is a critical goal to address greenhouse gas emissions and climate change. Major improvements have made wind and solar power increasingly cost-competitive with fossil fuels. However, the inherent intermittency of renewable power sources motivates pairing these resources with energy storage. Electrochemical energy storage in batteries is widely used in many fields and increasingly for grid-level storage, but current battery technologies still fall short of performance, safety, and cost. This review focuses on sodium metal halide (Na-MH) batteries, such as the well-known Na-NiCl2 battery, as a promising solution to safe and economical grid-level energy storage. Important features of conventional Na-MH batteries are discussed, and recent literature on the development of intermediate-temperature, low-cost cathodes for Na-MH batteries is highlighted. By employing lower cost metal halides (e.g., FeCl2, and ZnCl2, etc.) in the cathode and operating at lower temperatures (e.g., 190 °C vs. 280 °C), new Na-MH batteries have the potential to offer comparable performance at much lower overall costs, providing an exciting alternative technology to enable widespread adoption of renewables-plus-storage for the grid.

Daily fluctuations in occupation with and worry about COVID-19.

In the first week after the first COVID-19 patient was reported in the Netherlands, we conducted a pre-registered momentary assessment study (7 surveys per day, 50 participants, 7 days) to study the dynamic relationship between individuals' occupation with and worries about COVID-19 in daily life, and the moderating role of neuroticism in this relationship. At the group level, higher scores on occupation and worry co-occurred, and occupation predicted worry 1 h later, but not vice versa. There were substantial individual differences in the magnitudes and directions of the effects. For instance, occupation with COVID-19 was related to increases in worry for some but decreases in worry for others. Neuroticism did not predict any of these individual differences in the links between worry and occupation. This study suggests that it is important to go beyond group-level analyses and to account for individual differences in responses to COVID-19.

Faecal immunochemical testing and blood tests for prioritization of urgent colorectal cancer referrals in symptomatic patients: a 2-year evaluation.

BACKGROUND: A novel pathway incorporating faecal immunochemical testing (FIT) for rapid colorectal cancer diagnosis (RCCD) was introduced in 2017. This paper reports on the service evaluation after 2 years of pathway implementation. METHODS: The RCCD protocol was based on FIT, blood results and symptoms to stratify adult patients in primary care. Two-week-wait (2WW) investigation was indicated for patients with rectal bleeding, rectal mass and faecal haemoglobin (fHb) level of 10 µg Hb/g faeces or above or 4 µg Hb/g faeces or more in the presence of anaemia, low ferritin or thrombocytosis, in all other symptom groups. Patients with 100 µg Hb/g faeces or above had expedited investigation . A retrospective audit of colorectal cancer detected between 2017 and 2019 was conducted, fHb thresholds were reviewed and critically assessed for cancer diagnoses. RESULTS: In 2 years, 14788 FIT tests were dispatched with 13361 (90.4 per cent) completed returns. Overall, fHb was less than 4 µg Hb/g faeces in 9208 results (68.9 per cent), 4-9.9 µg Hb/g in 1583 (11.8 per cent), 10-99.9 µg Hb/g in 1850 (13.8 per cent) and 100 µg Hb/g faeces or above in 720 (5.4 per cent). During follow-up (median 10.4 months), 227 colorectal cancers were diagnosed. The cancer detection rate was 0.1 per cent in patients with fHb below 4 µg Hb/g faeces, 0.6 per cent in those with fHb 4-9.9 µg Hb/g faeces, 3.3 per cent for fHb 10-99.9 µg Hb/g faeces and 20.7 per cent for fHb 100 µg Hb/g faeces or above. The detection rate in the cohort with 10-19.9 µg Hb/g faeces was 1.4 per cent, below the National Institute for Health and Care Excellence threshold for urgent referral. The colorectal cancer rate in patients with fHb below 20 µg Hb/g faeces was less than 0.3 per cent. CONCLUSION: Use of FIT to "rule out" urgent referral from primary care misses a small number of cases. The threshold for referral may be adjusted with blood results to improve stratification .

[Clinical and sonographic examination findings in patients with carotid-cavernous sinus fistulas]. / Klinische und echographische Untersuchungsbefunde bei Patienten mit Carotis-Sinus-cavernosus-Fisteln.

BACKGROUND: Symptoms and clinical findings in patients with carotid-cavernous fistulas are specific. Nevertheless, they can be very mildly expressed. This study aims to point out the potential diagnostic value of ultrasound of the orbit. METHODS: A total of 25 patients with a reliable angiographic diagnosis of a fistula were reviewed retrospectively. We analyzed the symptoms, clinical findings and demonstrability in ultrasound of the orbit. RESULTS: The most common clinical findings were nerve palsy, dilation of episcleral vessels and exophthalmos. If an ultrasound had been part of the examination a dilation of the superior ophthalmic vein could be demonstrated in all cases. CONCLUSION: The expeditious ultrasound investigation provides valuable information for the diagnosis of red eyes which are resistant to treatment. The examiner has to consider a fistula and perform an ultrasound especially when diplopia has newly occurred. Finally, the expedient neuroimaging can be arranged.

[Contact lens-associated superficial stromal keratitis caused by Paecilomyces lilacinus]. / Kontaktlinsenassoziierte oberflächliche stromale Keratitis durch Paecilomyces lilacinus.

This article presents two cases of contact lens wearers with keratitis caused by Paecilomyces lilacinus. The special feature of these cases was the superficial manifestation of the infection in the upper stromal layer without infiltration into deeper layers. The pathogen was identified following epithelial debridement and corneal scraping. In both cases the fungal keratitis could be successfully managed by intensive topical treatment with voriconazole. Except for an epithelial debridement with EDTA chelation and an amniotic membrane transplantation in one case, no further surgical interventions were necessary.

Tissue paper-derived porous carbon encapsulated transition metal nanoparticles as advanced non-precious catalysts: Carbon-shell influence on the electrocatalytic behaviour.

Porous carbon encapsulated non-precious metal nanocatalysts have recently opened the ways towards the development of high-performance water remediation and energy conversion technologies. Herein, we report a facile, scalable and green synthetic methodology to fabricate porous carbon encapsulated transition metal nanocatalysts (M@TP: M = Cu, Ni, Fe and Co) using commercial tissue paper. The morphology, crystalline structure, chemical composition and textural properties of the M@TP nanocatalysts were thoroughly characterized. The catalytic activity of the M@TP nanocatalysts was investigated for the degradation of Congo red (CR) via peroxymonosulfate activation. Co@TP-6 was found to be the most active catalyst allowing 97.68% degradation in 30 min with a higher rate constant of 0.109 min-1. The nanocatalysts also displayed a carbon shell thickness-dependent electrocatalytic hydrogen evolution reaction (HER) activity, most likely due to the shielding effect of the carbon layers over the electron transfer (ET) processes at the metal core/carbon interfaces. Remarkably, the Ni@TP-6 electrocatalyst, with the smaller carbon shell thickness, showed the best electrocatalytic performance. They delivered an ultralow onset potential of -30 mV vs RHE, an overpotential of 105 mV at a current density of 10 mA·cm-2 and an excellent electrochemical stability to keep the 92% of the initial current applied after 25000 s, which is comparable with the HER activity of the state-of-the-art Ni-based catalysts.

GP access to FIT increases the proportion of colorectal cancers detected on urgent pathways in symptomatic patients in Nottingham.

OBJECTIVE: Service evaluation of GP access to Faecal Immunochemical Test (FIT) for colorectal cancer (CRC) detection in Nottinghamshire and use of FIT for "rule out", "rule in" and "first test selection". DESIGN: Retrospective audit of FIT results, CRC outcomes and resource utilisation before and after introduction of FIT in Primary Care in November 2017. Data from the new pathway up to December 2018 was compared with previous experience. RESULTS: Between November 2017 and December 2018, 6747 GP FIT test requests yielded 5733 FIT results, of which 4082 (71.2%) were <4.0 µg Hb/g faeces, 579 (10.1%) were 4.0-9.9 µg Hb/g faeces, 836 (14.6%) were 10.0-149.9 µg Hb/g faeces, and 236 (4.1%) were ≥150.0 µg Hb/g faeces. The proportion of "rule out" results <4.0 µg Hb/g faeces was significantly higher than in the Getting FIT cohort (71.2% vs 60.4%, Chi squared 42.8, p < 0.0001) and the proportion of "rule in" results ≥150.0 µg Hb/g faeces was significantly lower (4.1% vs 8.1%, Chi squared 27.3,P < 0.0001). There was a 33% rise in urgent referrals across Nottingham overall during the evaluation period. 2 CRC diagnoses were made in 4082 patients who had FIT<4.0 µg Hb/g faeces. 58.4% of new CRC diagnoses associated with a positive FIT were early stage cancers (Stage I and II). The proportion of all CRC diagnoses that follow an urgent referral s rose after introduction of FIT. CONCLUSIONS: FIT allows GP's to select a more appropriate cohort for urgent investigation without a large number of missed diagnoses. FIT appears to promise a "stage migration" effect which may ultimately improve CRC outcomes.