The limits of filopodium stability

Filopodia are long, finger-like membrane tubes supported by cytoskeletal filaments. Their shape is determined by the stiffness of the actin filament bundles found inside them and by the interplay between the surface tension and bending rigidity of the membrane. Although one might expect the Euler buckling instability to limit the length of filopodia, we show through simple energetic considerations that this is in general not the case. By further analyzing the statics of filaments inside membrane tubes, and through computer simulations that capture membrane and filament fluctuations, we show under which conditions filopodia of arbitrary lengths are stable. We discuss several in vitro experiments where this kind of stability has already been observed. Furthermore, we predict that the filaments in long, stable filopodia adopt a helical shape

Intraocular Pressure Correlates with Optic Nerve Sheath Diameter in Patients with Normal Tension Glaucoma

PURPOSE: 1. Identify differences in optic nerve sheath diameter (ONSD) as an indirect measure of intracranial pressure (ICP) in glaucoma patients and a healthy population. 2. Identify variables that may correlate with ONSD in primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) patients. METHODS: Patients with NTG (n = 46) and POAG (n = 61), and healthy controls (n = 42) underwent B-scan ultrasound measurement of ONSD by an observer masked to the patient diagnosis. Intraocular pressure (IOP) was measured in all groups, with additional central corneal thickness (CCT) and visual field defect measurements in glaucomatous patients. Only one eye per patient was selected. Kruskal-Wallis or Mann-Whitney were used to compare the different variables between the diagnostic groups. Spearman correlations were used to explore relationships among these variables. RESULTS: ONSD was not significantly different between healthy, NTG and POAG patients (6.09 ± 0.78, 6.03 ± 0.69, and 5.71 ± 0.83 respectively; p = 0.08). Visual field damage and CCT were not correlated with ONSD in either of the glaucoma groups (POAG, p = 0.31 and 0.44; NTG, p = 0.48 and 0.90 respectively). However, ONSD did correlate with IOP in NTG patients (r = 0.53, p  0.25 in all groups). CONCLUSIONS: Indirect measurements of ICP by ultrasound assessment of the ONSD may provide further insights into the retrolaminar pressure component in glaucoma. The correlation of ONSD with IOP solely in NTG patients suggests that the translaminar pressure gradient may be of particular importance in this type of glaucoma

Feeling Seen, Being Heard:Perspectives of Patients Suffering from Mental Illness on the Possibility of Physician-Assisted Death in the Netherlands

Physician-assisted death (PAD) for patients suffering from a mental illness is allowed in the Netherlands under certain conditions but is a very controversial topic, mainly discussed by ethicists and physicians. The voice of the patient is rarely included in the debate, so we know little about what their views on the topic are. We aim to understand the views of patients with mental illness and wish to die with regard to the possibility of PAD in the Netherlands. The data for this qualitative study were collected through 21 in-depth interviews with Dutch patients who have a wish for PAD as a result of suffering from a mental illness. We identified four themes in relation to the meaning of PAD for the patients suffering from mental illness and wish to die. These themes are (1) Autonomy and self-determination, (2) ending the suffering, (3) recognition, and (4) a dignified end-of-life. The option of PAD for patients suffering from mental illnesses was considered of great importance to the patients who have a wish to die. We highlight the importance of ‘recognition’ for the situation of the patient, as this could lead to new perspective. We argue that psychiatrists need to reflect on providing this recognition in earlier phases of treatment, taking seriously and discussing a wish for PAD in treatment is beneficial to patients. It provides space for the patient to discuss their wishes and could cause them not wanting to die anymore

The Use of Telehealth Technology in Assessing the Accuracy of Self-Reported Weight and the Impact of a Daily Immediate-Feedback Intervention among Obese Employees

Objective. To determine the accuracy of self-reported body weight prior to and following a weight loss intervention including daily self-weighing among obese employees. Methods. As part of a 6-month randomized controlled trial including a no-treatment control group, an intervention group received a series of coaching calls, daily self-weighing, and interactive telemonitoring. The primary outcome variable was the absolute discrepancy between self-reported and measured body weight at baseline and at 6 months. We used general linear mixed model regression to estimate changes and differences between study groups over time. Results. At baseline, study participants underreported their weight by an average of 2.06 (se = 0.33) lbs. The intervention group self-reported a smaller absolute body weight discrepancy at followup than the control group. Conclusions. The discrepancy between self-reported and measured body weight appears to be relatively small, may be improved through daily self-monitoring using immediate-feedback telehealth technology, and negligibly impacts change in body weight

Clinical radiography education across Europe

Purpose: To establish a picture of clinical education models within radiography programmes across Europe by surveying higher education institutions registered as affiliate members of the European Federation of Radiography Societies (EFRS). Method: An online survey was developed to ascertain data on: practical training, supervisory arrangements, placement logistics, quality assurance processes, and the assessment of clinical competencies. Responses were identifiable in terms of educational institution and country. All educational institutions who were affiliate members at the time of the study were invited to participate (n=46). Descriptive and thematic analyses are reported. Results: A response rate of 82.6% (n=38) was achieved from educational institutions representing 21 countries. Over half of responding institutions (n=21) allocated in excess of 60 European Credit Transfer and Accumulation System (ECTS) credits to practical training. In nearly three-quarters of clinical placements there was a dedicated clinical practice supervisor in place; two-thirds of these were employed directly by the hospital. Clinical practice supervisors were typically state registered radiographers, who had a number of years of clinical experience and had received specific training for the role. Typical responsibilities included monitoring student progress, providing feedback and completing paperwork, this did however vary between respondents. In almost all institutions there were support systems in place for clinical placement supervisors within their roles. Conclusions: Similarities exist in the provision of clinical radiography education across Europe. Clinical placements are a core component of radiography education and are supported by experienced clinical practice supervisors. Mechanisms are in place for the selection, training and support of clinical practice supervisors. Professional societies should work collaboratively to establish guidelines for effective clinical placements

Losing sight of Luck: Automatic approach tendencies toward gambling cues in Canadian moderate- to high-risk gamblers – A replication study

Evidence for approach bias tendencies to underly automatic behavioural impulses towards seeking out gambling activities in the presence of appetitive salient cues was first shown by Boffo et al. (2018) in a Dutch sample. Relative to non-problem gamblers, moderate-to-high-risk gamblers demonstrated stronger approach tendencies towards gambling-related stimuli compared with neutral ones. Moreover, gambling approach bias was associated with past-month gambling behaviour and predictive of gambling activity persistence over time. The current study aimed to replicate these findings within a Canadian sample evaluating the concurrent and longitudinal correlates of gambling approach bias. The study was conducted online, available throughout Canada. Twenty-seven non-treatment-seeking moderate-to-high-risk gamblers and 26 non-problem gamblers community-recruited via multiple channels (i.e., internet and newspaper advertisements, land-based flyers, and university recruitment portals). Participants completed two online assessment sessions 6-months apart. Each session included (1) self-report measures of gambling behaviour (frequency, duration, and expenditure), (2) self-report assessment of problem gambling severity (PGSI), and (3) a gambling approach-avoidance task, utilising culturally relevant stimuli tailored to individual gambling habits. However, our study failed to replicate Boffo et al. (2018) findings in a Canadian sample. Relative to non-problem gamblers, moderate-to-high-risk gamblers did not exhibit greater approach bias tendencies towards gambling-related stimuli compared to neutral stimuli. Moreover, gambling approach bias was not predictive of prospective gambling behaviour (frequency, duration, or expenditure) or severity of gambling problems. Reported results do not provide evidence for approach tendencies contributing to problematic gambling behaviour in a Canadian sample of moderate-to-high-risk gamblers compared to non-problematic gambler controls. Further replications on the topic are needed. Future research should evaluate approach tendencies within the gambling context, considering the potential impact of task reliability to assess approach bias in light of individual gambling modality preferences.</p

Peripheral neuropathy induced by combination chemotherapy of docetaxel and cisplatin.

Docetaxel, a new semisynthetic taxoid that has demonstrated promising activity as an antineoplastic agent, was administered in combination with cisplatin to 63 patients in a dose-escalating study. As both drugs were known to be potentially neurotoxic, peripheral neurotoxicity was prospectively assessed in detail. Neuropathy was evaluated by clinical sum-score for signs and symptoms and by measurement of the vibration perception threshold (VPT). The severity of neuropathy was graded according to the National Cancer Institute's 'Common Toxicity Criteria'. The docetaxel-cisplatin combination chemotherapy induced a predominantly sensory neuropathy in 29 (53%) out of 55 evaluable patients. At cumulative doses of both cisplatin and docetaxel above 200 mg m(-2), 26 (74%) out of 35 patients developed a neuropathy which was mild in 15, moderate in ten and severe in one patient. Significant correlations were present between both the cumulative dose of docetaxel and cisplatin and the post-treatment sum-score of neuropathy (P < 0.01) as well as the post-treatment VPT (P < 0.01). The neurotoxic effects of this combination were more severe than either cisplatin or docetaxel as single agent at similar doses

There and (slowly) back again: Entropy-driven hysteresis in a model of DNA overstretching

When pulled along its axis, double-stranded DNA elongates abruptly at a force of about 65 pN. Two physical pictures have been developed to describe this overstretched state. The first proposes that strong forces induce a phase transition to a molten state consisting of unhybridized single strands. The second picture instead introduces an elongated hybridized phase, called S-DNA, structurally and thermodynamically distinct from standard B-DNA. Little thermodynamic evidence exists to discriminate directly between these competing pictures. Here we show that within a microscopic model of DNA we can distinguish between the dynamics associated with each. In experiment, considerable hysteresis in a cycle of stretching and shortening develops as temperature is increased. Since there are few possible causes of hysteresis in a system whose extent is appreciable in only one dimension, such behavior offers a discriminating test of the two pictures of overstretching. Most experiments are performed upon nicked DNA, permitting the detachment (`unpeeling') of strands. We show that the long-wavelength progression of the unpeeled front generates hysteresis, the character of which agrees with experiment only if we assume the existence of S-DNA. We also show that internal melting (distinct from unpeeling) can generate hysteresis, the degree of which is strongly dependent upon the nonextensive loop entropy of single-stranded DNA.Comment: 18 pages, 10 figure