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Abstract Wildlife in cities divides people, with some animals bringing positive benefits and others causing conflict, for example due to property damage. Urban wildlife professionals from municipal administration, nature conservation, and hunting associations have a crucial role in shaping human‐wildlife relationships in cities and fostering conflict‐free coexistence. While many studies on urban wildlife have focused on the views of citizens, few have investigated the perspectives of experts to date. To address this knowledge gap, we interviewed 36 urban wildlife professionals giving guidance in the context of urban wildlife management, either in one of the four largest German cities by population (Berlin, Hamburg, Munich and Cologne) or at the national level. Red foxes, wild boars, raccoons, stone martens and Eurasian beavers were the five mammal species most frequently highlighted in interviews to cause human‐wildlife conflicts. The interviewees saw wild boars and raccoons as the most controversial urban wild mammals but emphasized the need to create refuges for beavers and better inform the public about foxes. Management in terms of public outreach, urban planning and population control, as well as establishing official contact points and stricter fines of activities violating regulations were highlighted as important elements of a toolkit to manage urban wildlife conflicts. Read the free Plain Language Summary for this article on the Journal blog.

Abstract While reintroductions of regionally extinct native species usually benefit ecosystems, reintroduced animals often struggle to locate appropriate habitats where they can establish themselves without conflict with humans. European beavers (Castor fiber) were successfully reintroduced to Germany almost 60 years ago and have reached high abundances again. As beavers can damage trees and change landscapes, they are increasingly in conflict with humans. We investigated human perceptions of beavers in Germany using an online survey, as they are an example of a reintroduced species with an expanding population and potential conflicts with humans. We asked participants about their emotions (anger, fear, interest, joy) towards beavers and what they consider to be acceptable beaver habitats. Of nearly 1500 survey participants, 803 (53%) were from the general public, 475 (32%) from the agricultural sector and 219 (15%) from forestry. People in these sectors had very different perspectives: beavers were positively perceived by the general public, but negatively by stakeholders working in agriculture and forestry. Independently of stakeholder groups, we also found regional differences, as participants from Bavaria—the German state with the highest beaver densities—viewed beavers more negatively than those from the rest of Germany. Zoos and wildlife parks, as well as urban and nature conservation areas, were considered to be the most acceptable habitats for beavers, whereas survey participants did not accept private gardens and cultivated areas as beaver habitats. We discuss the sources of negative emotions towards beavers and how ecologically suitable habitats differ from those that appear acceptable by humans. Even 60 years after their reintroduction, beavers in Germany are still being recognized as both a novelty and a nuisance. Our findings highlight the need for active beaver management and increased public engagement to enable positive coexistence between beavers and humans in Germany. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Background Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC‐specific survival (BCSS) compared to non‐carriers. Aim To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Methods Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow‐up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi‐state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. Results There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55–0.78)]. No association was observed with radiotherapy. Results from the multi‐state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non‐carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09–1.56)]. Conclusion Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk.

Abstract Objectives Oral rehabilitation can be a challenge in patients on high‐dose antiresorptive medication (HDAR), especially if the alveolar anatomy has changed due to previous medication‐related osteonecrosis of the jaw (MRONJ) resection. In healthy patients, dental implant treatment has found wide acceptance in prosthetic rehabilitation as it increases the patient's oral health‐related quality of life. However, it is considered contraindicated in patients on HDAR due to the risk of MRONJ, although a recent feasibility study indicates that implant treatment may indeed be an option in these patients. The aim of the present case report is to illustrate the risk of MRONJ in a patient with cancer on HDAR and to discuss the reasons behind the outcomes of the implant treatment. Materials and Methods A patient with prostate cancer with bone metastases on high‐dose denosumab therapy with previous MRONJ had four implants inserted bilaterally in the maxilla (14, 13, 23, 24). Two identical implant‐supported screw‐retained cantilever bridges were fabricated. The patient was followed for more than 1 year. Results and Conclusion Peri‐implantitis, and/or MRONJ, was diagnosed around two of the implants (23, 24), probably induced by crestal bone trauma from a healing abutment and/or a misfitting prosthetic reconstruction. A peri‐implantitis operation was performed, but without the desired response, and the two implants (23, 24) were later removed in an MRONJ resection. The implants on the other side of the maxilla (14, 13) remained without complications. Dental implant treatment is feasible in patients on HDAR, but comorbidities (e.g., diabetes mellitus) and polypharmacy (e.g., chemotherapy and steroids) may add to the risk of implant failure. Minimal trauma surgery and prosthodontics are crucial to increase the chance of successful healing in an HDAR patient.

Abstract GDC‐0334 is a novel small molecule inhibitor of transient receptor potential cation channel member A1 (TRPA1), a promising therapeutic target for many nervous system and respiratory diseases. The pharmacokinetic (PK) profile and pharmacodynamic (PD) effects of GDC‐0334 were evaluated in this first‐in‐human (FIH) study. A starting single dose of 25 mg was selected based on integrated preclinical PK, PD, and toxicology data following oral administration of GDC‐0334 in guinea pigs, rats, dogs, and monkeys. Human PK and PK‐PD of GDC‐0334 were characterized after single and multiple oral dosing using a population modeling approach. The ability of GDC‐0334 to inhibit dermal blood flow (DBF) induced by topical administration of allyl isothiocyanate (AITC) was evaluated as a target‐engagement biomarker. Quantitative models were developed iteratively to refine the parameter estimates of the dose‐concentration‐effect relationships through stepwise estimation and extrapolation. Human PK analyses revealed that bioavailability, absorption rate constant, and lag time increase when GDC‐0334 was administered with food. The inhibitory effect of GDC‐0334 on the AITC‐induced DBF biomarker exhibited a clear sigmoid‐Emax relationship with GDC‐0334 plasma concentrations in humans. This study leveraged emerging preclinical and clinical data to enable iterative refinement of GDC‐0334 mathematical models throughout the FIH study for dose selection in subsequent cohorts throughout the study. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? GDC‐0334 is a novel, small molecule TRPA1 inhibitor and a pharmacokinetic‐pharmacodynamic (PK‐PD) modeling strategy could be implemented in a systematic and step‐wise manner to build and learn from emerging data for early clinical development. WHAT QUESTION DID THIS STUDY ADDRESS? Can noncompartmental and population‐based analyses be used to describe the PK and PD characteristics of GDC‐0334 in preclinical and clinical studies? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? GDC‐0334 exposure generally increased with dose in rats, dogs, and monkeys. The starting dose (25 mg) in the clinical study was determined based on the preclinical data. GDC‐0334 exhibited linear PK in humans and the bioavailability was increased with food. The inhibitory effect of GDC‐0334 on dermal blood flow induced by the TRPA1 agonist allyl isothiocyanate in humans indicates a clear PK‐PD relationship. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? The models developed based on TRPA1 agonist‐induced dermal blood flow inhibition data can be used to predict PK‐PD relationships in future preclinical and clinical studies evaluating new drug entities that target TRPA1.

Abstract Background Aging is associated with sarcopenia (low muscle mass) and dynapenia (low muscle strength) leading to disability and mortality. Widely used previous cut‐points for sarcopenia were established from dated, small, or pooled cohorts. We aimed to identify cut‐points of low strength as a determinant of impaired physical performance and cut‐points of low appendicular lean mass (ALM) as a predictor of low strength in a single, large, and contemporary cohort of community‐dwelling older adults and compare these criteria with others. Methods Cross‐sectional analyses were conducted on baseline data from 4725 and 4363 community‐dwelling men and women (65–86 years, 96.8% Caucasian) of the Canadian longitudinal study on aging comprehensive cohort. Physical performance was evaluated from gait speed, timed up‐and‐go, chair rise, and balance tests; a weighted‐sum score was computed using factor analysis. Strength was measured by handgrip dynamometry; ALM, by dual‐energy X‐ray absorptiometry and ALM index (ALMI; kg/m2), was calculated. Classification and regression tree analyses determined optimal sex‐specific cut‐points of ALMI predicting low strength and of strength predicting impaired physical performance (score

A high-input voltage 2-phase series-capacitor (2-pscB) DC-DC buck converter is theoretically analyzed, designed, and implemented. A new design approach for an automatic current sharing scheme was presented for a 2-phase series-capacitor synchronous buck converter. The series-capacitor voltage is used to achieve current sharing between phases without a current sensing circuit or external control loop as each phase inductor charges and discharges the series capacitor to maintain its average capacitor voltage constant. A novel isolated gate driver circuit to accommodate an energy storage capacitor is proposed to deliver isolated gate voltages to the switching transistors. An I2 control scheme that uses only one feedback path control for the four gate drivers is proposed to enable higher voltage conversion. An experimental 110-12 V 6 A load prototype converter was designed, and its current sharing characteristics were experimentally verified.

Substantial progress has been made in identifying the extracellular signalling pathways that regulate neural stem and precursor cell biology in the central nervous system (CNS). The bone morphogenetic proteins (BMPs), in particular BMP4, are key players regulating neuronal and glial cell development from neural precursor cells in the embryonic, postnatal, and injured CNS. Here we review recent studies on BMP4 signalling in the generation of neurons, astrocytes, and oligodendroglial cells in the CNS. We also discuss putative mechanisms that BMP4 may utilise to influence glial cell development following CNS injury and highlight some questions for further research.

Purpose. To report 7 cases of intraocular lens (IOL) opacification following treatment of postoperative anterior chamber fibrin with recombinant tissue plasminogen activator (rtPA) after cataract surgery. Methods. Retrospective case series of 7 eyes in 7 patients who developed IOL opacification after receiving rtPA for anterior chamber inflammatory membrane formation resulting from phacoemulsification cataract surgery. Three explanted IOLs were investigated with light microscopy, histochemical analysis, scanning electron microscopy, and X-ray spectrometry. Results. All patients underwent uncomplicated cataract surgery and posterior chamber hydrophilic IOL implantation. Anterior chamber inflammatory membranes developed between 1 and 4 weeks of surgery and were treated with intracameral rtPA. IOL opacification was noted between 4 weeks and 6 years after rtPA treatment with reduced visual acuity, and IOL exchange was carried out in 3 patients. Light microscopy evaluation revealed diffuse fine granular deposits on the anterior surface/subsurface of IOL optic that stained positive for calcium salts. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectrometry (EDS) confirmed the presence of calcium and phosphate on the IOL. Conclusions. Intracameral rtPA, though rapidly effective in the treatment of anterior chamber inflammatory membranes following cataract surgery, may be associated with IOL opacification.