Combining gradient ascent search and support vector machines for effective autofocus of a field emission–scanning electron microscope

Autofocus is an important issue in electron microscopy, particularly at high magnification. It consists in searching for sharp image of a specimen, that is corresponding to the peak of focus. The paper presents a machine learning solution to this issue. From seven focus measures, support vector machines fitting is used to compute the peak with an initial guess obtained from a gradient ascent search, that is search in the direction of higher gradient of focus. The solution is implemented on a Carl Zeiss Auriga FE-SEM with a three benchmark specimen and magnification ranging from x300 to x160 000. Based on regularized nonlinear least squares optimization, the solution overtakes the literature non-regularized search and Fibonacci search methods: accuracy improvement ranges from 1.25 to 8 times, fidelity improvement ranges from 1.6 to 28 times, and speed improvement ranges from 1.5 to 4 times. Moreover, the solution is practical by requiring only an off-line easy automatic train with cross-validation of the support vector machines

Sacral nerve stimulation in patients with ileal pouch-anal anastomosis

Purpose: Functional results after proctocolectomy and ileal pouch-anal anastomosis (IPAA) are generally good. However, some patients suffer from high stool frequency or fecal incontinence. Sacral nerve stimulation (SNS) may represent a therapeutic alternative in these patients, but little is known about indication and results. The aim of this study was to evaluate incontinence after IPAA and demonstrate SNS feasibility in these patients. Methods: This retrospective study includes patients who received a SNS between 1993 and 2020 for increased stool frequency or fecal incontinence after proctocolectomy with IPAA for ulcerative colitis. Proctocolectomy was performed in a two- or three-step approach with ileostomy closure as the last step. Demographic, follow-up data and functional results were obtained from the hospital database. Results: SNS was performed in 23 patients. Median follow-up time after SNS was 6.5 years (min. 4.2-max. 8.8). Two patients were lost to follow-up. The median time from ileostomy closure to SNS implantation was 6 years (min. 0.5-max. 14.5). Continence after SNS improved in 16 patients (69%) with a median St. Marks score for anal incontinence of 19 (min. 4-max. 22) before SNS compared to 4 (0-10) after SNS placement (p = 0.012). In seven patients, SNS therapy was not successful. Conclusion: SNS implantation improves symptoms in over two-thirds of patients suffering from high stool frequency or fecal incontinence after proctocolectomy with IPAA. Awareness of the beneficial effects of SNS should be increased in physicians involved in the management of these patients

Unabhängig, aber arm: Zur Dauer des Nichtbezuges von Sozialhilfe

Es gibt Menschen, die unterhalb des Existenzminimums leben und trotzdem keine Sozialhilfe beziehen. In einer Studie für die Sozialhilfe Basel-Stadt wurde erstmals untersucht, ob es sich beim Nichtbezug um ein kurzfristiges oder länger andauerndes Phänomen handelt. Was bedeuten die Erkenntnisse für die Armutsbekämpfung

Exercise reduces systemic immune inflammation index (SII) in childhood cancer patients

While exercise and physical activity have been suggested to reduce mortality and symptoms in cancer, knowledge on these associations in patients with childhood cancer (CCPs) is sparse. Anti-inflammatory properties of exercise might mediate these beneficial effects. We investigated the influence of exercise on the inflammation markers neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic-immune-inflammation index (SII) and associations to patient-reported-outcomes in CCPs in a randomized-controlled trial. Results show associations between inflammation markers and patient-reported outcomes. Compared to the control group, SII was significantly reduced following exercise (p=0.036). Anti-inflammatory effects of exercise are also present in CCPs and may underlie exercise-induced benefits on symptoms. Clinical Trial Registration Number: NCT0261202

High resilience of carbon transport in long-term drought-stressed mature Norway spruce trees within 2 weeks after drought release

Under ongoing global climate change, drought periods are predicted to increase in frequency and intensity in the future. Under these circumstances, it is crucial for tree\u27s survival to recover their restricted functionalities quickly after drought release. To elucidate the recovery of carbon (C) transport rates in c. 70-year-old Norway spruce (Picea abies [L.] KARST.) after 5 years of recurrent summer droughts, we conducted a continuous whole-tree $^{13}$C labeling experiment in parallel with watering. We determined the arrival time of current photoassimilates in major C sinks by tracing the $^{13}$C label in stem and soil CO$_{2}$ efflux, and tips of living fine roots. In the first week after watering, aboveground C transport rates (CTR) from crown to trunk base were still 50% lower in previously drought-stressed trees (0.16 ± 0.01 m h$^{-1}$) compared to controls (0.30 ± 0.06 m h$^{-1}$). Conversely, CTR below ground, that is, from the trunk base to soil CO$_{2}$ efflux were already similar between treatments (c. 0.03 m h$^{-1}$). Two weeks after watering, aboveground C transport of previously drought-stressed trees recovered to the level of the controls. Furthermore, regrowth of water-absorbing fine roots upon watering was supported by faster incorporation of $^{13}$C label in previously drought-stressed (within 12 ± 10 h upon arrival at trunk base) compared to control trees (73 ± 10 h). Thus, the whole-tree C transport system from the crown to soil CO$_{2}$ efflux fully recovered within 2 weeks after drought release, and hence showed high resilience to recurrent summer droughts in mature Norway spruce forests. This high resilience of the C transport system is an important prerequisite for the recovery of other tree functionalities and productivity

MEndoB, a chimeric lysin featuring a novel domain architecture and superior activity for the treatment of staphylococcal infections

One of the most pressing challenges of our era is the rising occurrence of bacteria that are resistant to antibiotics. Staphylococci are prominent pathogens in humans, which have developed multiple strategies to evade the effects of antibiotics. Infections caused by these bacteria have resulted in a high burden on the health care system and a significant loss of lives. In this study, we have successfully engineered lytic enzymes that exhibit an extraordinary ability to eradicate staphylococci. Our findings substantiate the importance of meticulous lead candidate selection to identify therapeutically promising peptidoglycan hydrolases with unprecedented activity. Hence, they offer a promising new avenue for treating staphylococcal infections

Dynamics of initial carbon allocation after drought release in mature Norway spruce—Increased belowground allocation of current photoassimilates covers only half of the carbon used for fine‐root growth

After drought events, tree recovery depends on sufficient carbon (C) allocation to the sink organs. The present study aimed to elucidate dynamics of tree-level C sink activity and allocation of recent photoassimilates (C$_{new}$) and stored C in c. 70-year-old Norway spruce (Picea abies) trees during a 4-week period after drought release. We conducted a continuous, whole-tree $^{13}$C labeling in parallel with controlled watering after 5 years of experimental summer drought. The fate of C$_{new}$ to growth and CO$_{2}$ efflux was tracked along branches, stems, coarse- and fine roots, ectomycorrhizae and root exudates to soil CO$_{2}$ efflux after drought release. Compared with control trees, drought recovering trees showed an overall 6% lower C sink activity and 19% less allocation of C$_{new}$ to aboveground sinks, indicating a low priority for aboveground sinks during recovery. In contrast, fine-root growth in recovering trees was seven times greater than that of controls. However, only half of the C used for new fine-root growth was comprised of C$_{new}$ while the other half was supplied by stored C. For drought recovery of mature spruce trees, in addition to C$_{new}$, stored C appears to be critical for the regeneration of the fine-root system and the associated water uptake capacity

IGF1R is a potential new therapeutic target for HGNET-BCOR brain tumor patients

(1) Background: The high-grade neuroepithelial tumor of the central nervous system with BCOR alteration (HGNET-BCOR) is a highly malignant tumor. Preclinical models and molecular targets are urgently required for this cancer. Previous data suggest a potential role of insulin-like growth factor (IGF) signaling in HGNET-BCOR. (2) Methods: The primary HGNET-BCOR cells PhKh1 were characterized by western blot, copy number variation, and methylation analysis and by electron microscopy. The expression of IGF2 and IGF1R was assessed by qRT-PCR. The effect of chemotherapeutics and IGF1R inhibitors on PhKh1 proliferation was tested. The phosphorylation of IGF1R and downstream molecules was assessed by western blot. (3) Results: Phkh1 cells showed a DNA methylation profile compatible with the DNA methylation class “HGNET-BCOR” and morphologic features of cellular cannibalism. IGF2 and IGF1R were highly expressed by three HGNET-BCOR tumor samples and PhKh1 cells. PhKh1 cells were particularly sensitive to vincristine, vinblastine, actinomycin D (IC50 < 10 nM for all drugs), and ceritinib (IC50 = 310 nM). Ceritinib was able to abrogate the proliferation of PhKh1 cells and blocked the phosphorylation of IGF1R and AKT. (4) Conclusion: IGF1R is as an attractive target for the development of new therapy protocols for HGNET-BCOR patients, which may include ceritinib and vinblastine