Spin-asymmetric graphene nanoribbons in graphane on silicon dioxide

Hydrogenated graphene, graphane, is studied on oxygen-terminated silicon dioxide substrate using ab initio calculations. A structure with hydrogenation only on one side of the graphene layer is found stable and its hydrogen configurations are presented. Additionally, we form zigzag graphene nanoribbons by selectively removing hydrogens from the epitaxial graphane layer. In these ribbons, the spin degeneracy of the freestanding antiferromagnetic zigzag ribbons is broken, and band gaps of different magnitude emerge for the opposite spin species. This degeneracy breaking is due to a charge imbalance in the substrate below the ribbon, introduced through the asymmetric alignment of the substrate atoms with respect to the edges of the graphene ribbon

Quantum confined electronic states in atomically well-defined graphene nanostructures

Despite the enormous interest in the properties of graphene and the potential of graphene nanostructures in electronic applications, the study of quantum confined states in atomically well-defined graphene nanostructures remains an experimental challenge. Here, we study graphene quantum dots (GQDs) with well-defined edges in the zigzag direction, grown by chemical vapor deposition (CVD) on an iridium(111) substrate, by low-temperature scanning tunneling microscopy (STM) and spectroscopy (STS). We measure the atomic structure and local density of states (LDOS) of individual GQDs as a function of their size and shape in the range from a couple of nanometers up to ca. 20 nm. The results can be quantitatively modeled by a relativistic wave equation and atomistic tight-binding calculations. The observed states are analogous to the solutions of the text book "particle-in-a-box" problem applied to relativistic massless fermions.Comment: accepted for publication in Phys. Rev. Let

Haptoglobin Hp1 Variant Does Not Associate with Small Vessel Disease

Haptoglobin (Hp) is a plasma protein that binds free hemoglobin and protects tissues from oxidative damage. An Hp2 allele has been associated with an increased risk of cardiovascular complications. On the other hand, recent studies have suggested that Hp1 allele increases risk to develop severe cerebral small vessel disease. We aimed to replicate this finding in a first-ever stroke patient cohort. Hp was genotyped by PCR and gel electrophoresis in the Helsinki Stroke Aging Memory Study in patients with DNA and magnetic resonance imaging (MRI) available (SAM; n = 316). Lacunar infarcts and white matter lesions (WML) classified by Fazekas grading from brain MRI were associated with Hp genotypes. As population controls, we used participants of Cardiovascular diseases-a sub study of Health 2000 Survey (n = 1417). In the SAM cohort, 63.0% of Hp1-1 carriers (n = 46), 52.5% of Hp1-2 carriers (n = 141) and 51.2% of Hp2-2 carriers (n = 129) had severe WML (p = 0.372). There was no difference in severe WMLs between Hp1-1 vs. Hp1-2 and Hp2-2 carriers (p = 0.201). In addition, 68.9% of Hp1-1 carriers (n = 45), 58.5% of Hp1-2 carriers (n = 135), and 61.8% of Hp2-2 carriers (n = 126) had one or more lacunar lesions (p = 0.472). There was no difference in the number of patients with at least one lacunar infarct between Hp1-1 vs. Hp1-2 and Hp2-2 groups (p = 0.322). Neither was there any difference when diabetic patients (type I and II) were examined separately. Hp1 allele is not associated with an increased risk for cerebral small vessel disease in a well-characterized Finnish stroke patient cohort

How communication affects prescription decisions in consultations for acute illness in children:a systematic review and meta-ethnography

BACKGROUND: Communication within primary care consultations for children with acute illness can be problematic for parents and clinicians, with potential misunderstandings contributing to over–prescription of antibiotics. This review aimed to synthesise the evidence in relation to communication and decision making in consultations for children with common acute illness. METHODS: A systematic search of MEDLINE, EMBASE, CINAHL, PsycINFO, SSCI, SIGLE, Dissertation Express and NHS economic evaluation databases was conducted. Studies of primary care settings in high income countries which made direct observations of consultations and reported qualitative data were included. Included studies were appraised using the process recommended by the Cochrane Qualitative Methods Group. Credibility was assessed as high for most studies but transferability was usually assessed low or unclear. Data were synthesised using a meta–ethnographic approach. RESULTS: Thirty–five papers and 2 theses reporting on 13 studies were included, 7 of these focussed on children with respiratory tract infections (RTI) and the remaining 6 included children with any presenting illness. Parent communication focussed on their concerns and information needs, whereas clinician communication focussed on diagnosis and treatment decisions. During information exchanges, parents often sought to justify the need for the consultation, while clinicians frequently used problem minimising language, resulting in parents and clinicians sometimes talking at cross–purposes. In the context of RTIs, a range of parent communication behaviours were interpreted by clinicians as indicating an expectation for antibiotics; however, most were ambiguous and could also be interpreted as raising concerns or requests for further information. The perceived expectation for antibiotics often changed clinician decision making into clinician–parent negotiation. CONCLUSIONS: Misunderstandings occurred due to parents and clinicians talking at cross purposes about the ‘seriousness’ of the illness and because parents’ expressions of concern or requests for additional information were sometimes perceived as a challenge to the clinicians’ diagnosis or treatment decision. This modifiable problem may be an important contribution to the unnecessary and unwanted prescribing of antibiotics. Primary care clinicians should be offered training to understand parent communication primarily as expressions of concern or attempts at understanding and always to check rather than infer parental expectations

Expected impact of MRI-related interreader variability on ProScreen prostate cancer screening trial: a pre-trial validation study

Background: The aim of this study is to investigate the potential impact of prostate magnetic resonance imaging (MRI) -related interreader variability on a population-based randomized prostate cancer screening trial (ProScreen). Methods: From January 2014 to January 2018, 100 men aged 50-63 years with clinical suspicion of prostate cancer (PCa) in Helsinki University Hospital underwent MRI. Nine radiologists individually reviewed the pseudonymized MRI scans of all 100 men in two ProScreen trial centers. All 100 men were biopsied according to a histological composite variable comprising radical prostatectomy histology (N = 38) or biopsy result within 1 year from the imaging (N = 62). Fleiss' kappa (kappa) was used to estimate the combined agreement between all individual radiologists. Sample data were subsequently extrapolated to 1000-men subgroups of the ProScreen cohort. Results: Altogether 89% men of the 100-men sample were diagnosed with PCa within a median of 2.4 years of follow-up. Clinically significant PCa (csPCa) was identified in 76% men. For all PCa, mean sensitivity was 79% (SD +/- 10%, range 62-96%), and mean specificity 60% (SD +/- 22%, range 27-82%). For csPCa (Gleason Grade 2-5) MRI was equally sensitive (mean 82%, SD +/- 9%, range 67-97%) but less specific (mean 47%, SD +/- 20%, range 21-75%). Interreader agreement for any lesion was fair (kappa 0.40) and for PI-RADS 4-5 lesions it was moderate (kappa 0.60). Upon extrapolating these data, the average sensitivity and specificity to a screening positive subgroup of 1000 men from ProScreen with a 30% prevalence of csPCa, 639 would be biopsied. Of these, 244 men would be true positive, and 395 false positive. Moreover, 361 men would not be referred to biopsy and among these, 56 csPCas would be missed. The variation among the radiologists was broad as the least sensitive radiologist would have twice as many men biopsied and almost three times more men would undergo unnecessary biopsies. Although the most sensitive radiologist would miss only 2.6% of csPCa (false negatives), the least sensitive radiologist would miss every third. Conclusions: Interreader agreement was fair to moderate. The role of MRI in the ongoing ProScreen trial is crucial and has a substantial impact on the screening process.Peer reviewe

Expected impact of MRI-related interreader variability on ProScreen prostate cancer screening trial: a pre-trial validation study

Background: The aim of this study is to investigate the potential impact of prostate magnetic resonance imaging (MRI) -related interreader variability on a population-based randomized prostate cancer screening trial (ProScreen). Methods: From January 2014 to January 2018, 100 men aged 50-63 years with clinical suspicion of prostate cancer (PCa) in Helsinki University Hospital underwent MRI. Nine radiologists individually reviewed the pseudonymized MRI scans of all 100 men in two ProScreen trial centers. All 100 men were biopsied according to a histological composite variable comprising radical prostatectomy histology (N = 38) or biopsy result within 1 year from the imaging (N = 62). Fleiss' kappa (kappa) was used to estimate the combined agreement between all individual radiologists. Sample data were subsequently extrapolated to 1000-men subgroups of the ProScreen cohort. Results: Altogether 89% men of the 100-men sample were diagnosed with PCa within a median of 2.4 years of follow-up. Clinically significant PCa (csPCa) was identified in 76% men. For all PCa, mean sensitivity was 79% (SD +/- 10%, range 62-96%), and mean specificity 60% (SD +/- 22%, range 27-82%). For csPCa (Gleason Grade 2-5) MRI was equally sensitive (mean 82%, SD +/- 9%, range 67-97%) but less specific (mean 47%, SD +/- 20%, range 21-75%). Interreader agreement for any lesion was fair (kappa 0.40) and for PI-RADS 4-5 lesions it was moderate (kappa 0.60). Upon extrapolating these data, the average sensitivity and specificity to a screening positive subgroup of 1000 men from ProScreen with a 30% prevalence of csPCa, 639 would be biopsied. Of these, 244 men would be true positive, and 395 false positive. Moreover, 361 men would not be referred to biopsy and among these, 56 csPCas would be missed. The variation among the radiologists was broad as the least sensitive radiologist would have twice as many men biopsied and almost three times more men would undergo unnecessary biopsies. Although the most sensitive radiologist would miss only 2.6% of csPCa (false negatives), the least sensitive radiologist would miss every third. Conclusions: Interreader agreement was fair to moderate. The role of MRI in the ongoing ProScreen trial is crucial and has a substantial impact on the screening process.Peer reviewe

Gene expression differences between stroke-associated and asymptomatic carotid plaques

Atherosclerotic carotid stenosis is an important risk factor for stroke. Carotid plaques (CPs) causing stroke may present a distinct type of molecular pathology compared with transient ischemic attack (TIA)-associated or asymptomatic plaques. We compared the gene expression profiles of CPs from stroke patients (n = 12) and asymptomatic patients (n = 9), both with similar risk factors and severity of carotid stenosis (>70%). Sixty probes showed over 1.5-fold expression difference at 5% false discovery rate. Functional clustering showed enrichment of genes in 51 GO categories and seven pathways, the most significant of which relate to extracellular-matrix interaction, PPAR gamma signaling, scavanger receptor activity, and lysosomal activity. Differential expression of ten genes was confirmed in an extended replication group (n = 43), where the most significant expression differences were found in CD36 (2.1-fold change, p = 0.005), CD163 (1.7-fold change, p = 0.007) and FABP4 (2.2-fold change, p = 0.015). These include four genes not previously linked to plaque destabilization: GLUL (2.2-fold change, p = 0.016), FUCA1 (2.2-fold change, p = 0.025), IL1RN (1.6-fold change, p = 0.034), and S100A8 (2.5-fold change, p = 0.047). Strong correlations were found to plaque ulceration, plaque hemorrhage, and markers of apoptosis and proliferation (activated caspase 3, TUNEL, and Ki67). Protein expression of these genes was confirmed by immunohistochemistry and was found in the atheromatous areas of CPs critical for plaque destabilization. This study presents a comprehensive transcriptional analysis of stroke-associated CPs and demonstrates a significant transcriptome difference between stroke-associated and asymptomatic CPs. Follow-up studies on the identified genes are needed to define whether they could be used as biomarkers of symptomatic CPs or have a role in plaque destabilization