Thermal induced deflection in atomic force microscopy cantilevers: analysis and solution

Atomic force microscopy (AFM) cantilevers are commonly made from two material layers: a reflective coating and structural substrate. Although effective, this can result in thermally induced cantilever deflection due to ambient and local temperature changes. While this has been previously documented, key aspects of this common phenomenon have been overlooked. This work explores the impact of thermally induced cantilever deflection when in- and out-of-contact, including the topographic scan artefacts produced. Scanning thermal microscopy probes were employed to provide direct cantilever temperature measurement from Peltier and microheater sources, whilst permitting cantilever deflection to be simultaneously monitored. Optical lever-based measurements of thermal deflection in the AFM were found to vary by up to 250% depending on the reflected laser spot location on the cantilever. This highlights AFM's inherent inability to correctly measure and account for thermal induced cantilever deflection in its feedback system. This is particularly problematic when scanning a tip in-contact with the surface, when probe behaviour is closer mechanically to that of a bridge than a cantilever regarding thermal bending. In this case, measurements of cantilever deflection and inferred surface topography contained significant artefacts and varied from negative to positive for different optical lever laser locations on the cantilevers. These topographic errors were measured to be up to 600 nm for a small temperature change of 2 K. However, all cantilevers measured showed a point of consistent, complete thermal deflection insensitivity 55% to 60% along their lengths. Positioning the reflected laser at this location, AFM scans exhibited improvements of up-to 97% in thermal topographic artefacts relative to other laser positions

Buffalo, Bush Meat, and the Zoonotic Threat of Brucellosis in Botswana

Brucellosis is a zoonotic disease of global importance infecting humans, domestic animals, and wildlife. Little is known about the epidemiology and persistence of brucellosis in wildlife in Southern Africa, particularly in Botswana.Archived wildlife samples from Botswana (1995-2000) were screened with the Rose Bengal Test (RBT) and fluorescence polarization assay (FPA) and included the African buffalo (247), bushbuck (1), eland (5), elephant (25), gemsbok (1), giraffe (9), hartebeest (12), impala (171), kudu (27), red lechwe (10), reedbuck (1), rhino (2), springbok (5), steenbok (2), warthog (24), waterbuck (1), wildebeest (33), honey badger (1), lion (43), and zebra (21). Human case data were extracted from government annual health reports (1974-2006).Only buffalo (6%, 95% CI 3.04%-8.96%) and giraffe (11%, 95% CI 0-38.43%) were confirmed seropositive on both tests. Seropositive buffalo were widely distributed across the buffalo range where cattle density was low. Human infections were reported in low numbers with most infections (46%) occurring in children (<14 years old) and no cases were reported among people working in the agricultural sector.Low seroprevalence of brucellosis in Botswana buffalo in a previous study in 1974 and again in this survey suggests an endemic status of the disease in this species. Buffalo, a preferred source of bush meat, is utilized both legally and illegally in Botswana. Household meat processing practices can provide widespread pathogen exposure risk to family members and the community, identifying an important source of zoonotic pathogen transmission potential. Although brucellosis may be controlled in livestock populations, public health officials need to be alert to the possibility of human infections arising from the use of bush meat. This study illustrates the need for a unified approach in infectious disease research that includes consideration of both domestic and wildlife sources of infection in determining public health risks from zoonotic disease invasions

A written self-help intervention for depressed adults comparing behavioural activation combined with physical activity promotion with a self-help intervention based upon behavioural activation alone: study protocol for a parallel group pilot randomised controlled trial (BAcPAc)

notes: PMCID: PMC4061537types: Journal Article© 2014 Farrand et al.; licensee BioMed Central Ltd.Challenges remain to find ways to support patients with depression who have low levels of physical activity (PA) to overcome perceived barriers and enhance the perceived value of PA for preventing future relapse. There is an evidence-base for behavioural activation (BA) for depression, which focuses on supporting patients to restore activities that have been avoided, but practitioners have no specific training in promoting PA. We aimed to design and evaluate an integrated BA and PA (BAcPAc) practitioner-led, written, self-help intervention to enhance both physical and mental health.NPRI-

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification