776 research outputs found
Controllable Photonic Time-Bin Qubits from a Quantum Dot
Photonic time bin qubits are well suited to transmission via optical fibres
and waveguide circuits. The states take the form , with and referring to
the early and late time bin respectively. By controlling the phase of a laser
driving a spin-flip Raman transition in a single-hole-charged InAs quantum dot
we demonstrate complete control over the phase, . We show that this
photon generation process can be performed deterministically, with only a
moderate loss in coherence. Finally, we encode different qubits in different
energies of the Raman scattered light, demonstrating wavelength division
multiplexing at the single photon level
Intra-ocular melanoma metastatic to an axillary lymph node: A case report
<p>Abstract</p> <p>Background</p> <p>Unusual metastatic presentation of intra-ocular melanoma.</p> <p>Study Design</p> <p>Case report.</p> <p>Discussion</p> <p>Extra-regional lymphatic spread of intra-ocular melanoma has not been reported previously in the literature. The usual pattern of metastasis for intra-ocular melanoma is hematogenous. There are few reports of regional spread to the maxillofacial bones. We report an interesting case of a 51 year old female with prior history of right eye melanoma, now presenting with metastasis to the left axilla, which is an extra-regional nodal basin.</p> <p>Conclusion</p> <p>In female patients presenting with an isolated axillary mass, with a negative breast work up and known prior history of melanoma, the differential diagnosis should include possible metastatic melanoma. Core biopsy will confirm the diagnosis and tailor subsequent management.</p
Prediction of melanoma metastasis by the Shields index based on lymphatic vessel density
<p>Abstract</p> <p>Background</p> <p>Melanoma usually presents as an initial skin lesion without evidence of metastasis. A significant proportion of patients develop subsequent local, regional or distant metastasis, sometimes many years after the initial lesion was removed. The current most effective staging method to identify early regional metastasis is sentinel lymph node biopsy (SLNB), which is invasive, not without morbidity and, while improving staging, may not improve overall survival. Lymphatic density, Breslow's thickness and the presence or absence of lymphatic invasion combined has been proposed to be a prognostic index of metastasis, by Shields et al in a patient group.</p> <p>Methods</p> <p>Here we undertook a retrospective analysis of 102 malignant melanomas from patients with more than five years follow-up to evaluate the Shields' index and compare with existing indicators.</p> <p>Results</p> <p>The Shields' index accurately predicted outcome in 90% of patients with metastases and 84% without metastases. For these, the Shields index was more predictive than thickness or lymphatic density. Alternate lymphatic measurement (hot spot analysis) was also effective when combined into the Shields index in a cohort of 24 patients.</p> <p>Conclusions</p> <p>These results show the Shields index, a non-invasive analysis based on immunohistochemistry of lymphatics surrounding primary lesions that can accurately predict outcome, is a simple, useful prognostic tool in malignant melanoma.</p
Biological diversification linked to environmental stabilization following the Sturtian Snowball glaciation
The body fossil and biomarker records hint at an increase in biotic complexity between the two Cryogenian Snowball Earth episodes (ca. 661 million to ≤650 million years ago). Oxygen and nutrient availability can promote biotic complexity, but nutrient (particularly phosphorus) and redox dynamics across this interval remain poorly understood. Here, we present high-resolution paleoredox and phosphorus phase association data from multiple globally distributed drill core records through the non-glacial interval. These data are first correlated regionally by litho- and chemostratigraphy, and then calibrated within a series of global chronostratigraphic frameworks. The combined data show that regional differences in postglacial redox stabilization were partly controlled by the intensity of phosphorus recycling from marine sediments. The apparent increase in biotic complexity followed a global transition to more stable and less reducing conditions in shallow to mid-depth marine environments and occurred within a tolerable climatic window during progressive cooling after post-Snowball super-greenhouse conditions
Histological validation of a type 1 diabetes clinical diagnostic model for classification of diabetes
This is the final version. Available on open access from Wiley via the DOI in this recordAims: Misclassification of diabetes is common due to an overlap in the clinical features of type 1 and type 2 diabetes. Combined diagnostic models incorporating clinical and biomarker information have recently been developed that can aid classification, but they have not been validated using pancreatic pathology. We evaluated a clinical diagnostic model against histologically defined type 1 diabetes. Methods: We classified cases from the Network for Pancreatic Organ donors with Diabetes (nPOD) biobank as type 1 (n = 111) or non-type 1 (n = 42) diabetes using histopathology. Type 1 diabetes was defined by lobular loss of insulin-containing islets along with multiple insulin-deficient islets. We assessed the discriminative performance of previously described type 1 diabetes diagnostic models, based on clinical features (age at diagnosis, BMI) and biomarker data [autoantibodies, type 1 diabetes genetic risk score (T1D-GRS)], and singular features for identifying type 1 diabetes by the area under the curve of the receiver operator characteristic (AUC-ROC). Results: Diagnostic models validated well against histologically defined type 1 diabetes. The model combining clinical features, islet autoantibodies and T1D-GRS was strongly discriminative of type 1 diabetes, and performed better than clinical features alone (AUC-ROC 0.97 vs. 0.95; P = 0.03). Histological classification of type 1 diabetes was concordant with serum C-peptide [median < 17 pmol/l (limit of detection) vs. 1037 pmol/l in non-type 1 diabetes; P < 0.0001]. Conclusions: Our study provides robust histological evidence that a clinical diagnostic model, combining clinical features and biomarkers, could improve diabetes classification. Our study also provides reassurance that a C-peptide-based definition of type 1 diabetes is an appropriate surrogate outcome that can be used in large clinical studies where histological definition is impossible. Parts of this study were presented in abstract form at the Network for Pancreatic Organ Donors Conference, Florida, USA, 19–22 February 2019 and Diabetes UK Professional Conference, Liverpool, UK, 6–8 March 2019.Diabetes UKNational Institutes of Health (NIH)National Institute for Health Research (NIHR)JDRFHelmsley Charitable Trus
Investigating hyper-vigilance for social threat of lonely children
The hypothesis that lonely children show hypervigilance for social threat was examined in a series of three studies that employed different methods including advanced eye-tracking technology. Hypervigilance for social threat was operationalized as hostility to ambiguously motivated social exclusion in a variation of the hostile attribution paradigm (Study 1), scores on the Children’s Rejection-Sensitivity Questionnaire (Study 2), and visual attention to socially rejecting stimuli (Study 3). The participants were 185 children (11 years-7 months to 12 years-6 months), 248 children (9 years-4 months to 11 years-8 months) and 140 children (8 years-10 months to 12 years-10 months) in the three studies, respectively. Regression analyses showed that, with depressive symptoms covaried, there were quadratic relations between loneliness and these different measures of hypervigilance to social threat. As hypothesized, only children in the upper range of loneliness demonstrated elevated hostility to ambiguously motivated social exclusion, higher scores on the rejection sensitivity questionnaire, and disengagement difficulties when viewing socially rejecting stimuli. We found that very lonely children are hypersensitive to social threat
Safety and effectiveness of SGLT2 inhibitors in a UK population with type 2 diabetes and aged over 70 years: an instrumental variable approach
This is the final version. Available on open access from Springer via the DOI in this recordData availability: CPRD data are available by application to the CPRD Independent Scientific Advisory Committee. R code to preproduce the analysis in this paper is available at https://github.com/Exeter-Diabetes/CPRD-Laura-SGLT2i-in-older-adultsAIMS/HYPOTHESIS: Older adults are under-represented in trials, meaning the benefits and risks of glucose-lowering agents in this age group are unclear. The aim of this study was to assess the safety and effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in people with type 2 diabetes aged over 70 years using causal analysis. METHODS: Hospital-linked UK primary care data (Clinical Practice Research Datalink, 2013-2020) were used to compare adverse events and effectiveness in individuals initiating SGLT2i compared with dipeptidyl peptidase-4 inhibitors (DPP4i). Analysis was age-stratified: <70 years (SGLT2i n=66,810, DPP4i n=76,172), ≥70 years (SGLT2i n=10,419, DPP4i n=33,434). Outcomes were assessed using the instrumental variable causal inference method and prescriber preference as the instrument. RESULTS: Risk of diabetic ketoacidosis was increased with SGLT2i in those aged ≥70 (incidence rate ratio compared with DPP4i: 3.82 [95% CI 1.12, 13.03]), but not in those aged <70 (1.12 [0.41, 3.04]). However, incidence rates with SGLT2i in those ≥70 was low (29.6 [29.5, 29.7]) per 10,000 person-years. SGLT2i were associated with similarly increased risk of genital infection in both age groups (incidence rate ratio in those <70: 2.27 [2.03, 2.53]; ≥70: 2.16 [1.77, 2.63]). There was no evidence of an increased risk of volume depletion, poor micturition control, urinary frequency, falls or amputation with SGLT2i in either age group. In those ≥70, HbA1c reduction was similar between SGLT2i and DPP4i (-0.3 mmol/mol [-1.6, 1.1], -0.02% [0.1, 0.1]), but in those <70, SGLT2i were more effective (-4 mmol/mol [4.8, -3.1], -0.4% [-0.4, -0.3]). CONCLUSIONS/INTERPRETATION: Causal analysis suggests SGLT2i are effective in adults aged ≥70 years, but increase risk for genital infections and diabetic ketoacidosis. Our study extends RCT evidence to older adults with type 2 diabetes.Medical Research Council (MRC)EFSD/Novo NordiskResearch EnglandWellcome TrustNational Institute for Health and Care Research (NIHR
Toward a Unified Genetic Map of Higher Plants, Transcending the Monocot-Dicot Divergence
Closely related (confamilial) genera often retain large chromosomal tracts in which gene order is colinear, punctuated by structural mutations such as inversions and translocations 1. To explore the possibility that conservation of gene order might extrapolate to more distantly related taxa, we first estimated an average structural mutation rate. Nine pairs of taxa, for which there exist both comparative genetic maps and plausible estimates of divergence time, showed an average of0.14 (±0.06) structural mutations per chromosome per million years of divergence (Myr; Table 1). This value is offered as a first approximation, acknowledging that refined comparative data and/or divergence estimates may impel revision
Quantum Computing
Quantum mechanics---the theory describing the fundamental workings of
nature---is famously counterintuitive: it predicts that a particle can be in
two places at the same time, and that two remote particles can be inextricably
and instantaneously linked. These predictions have been the topic of intense
metaphysical debate ever since the theory's inception early last century.
However, supreme predictive power combined with direct experimental observation
of some of these unusual phenomena leave little doubt as to its fundamental
correctness. In fact, without quantum mechanics we could not explain the
workings of a laser, nor indeed how a fridge magnet operates. Over the last
several decades quantum information science has emerged to seek answers to the
question: can we gain some advantage by storing, transmitting and processing
information encoded in systems that exhibit these unique quantum properties?
Today it is understood that the answer is yes. Many research groups around the
world are working towards one of the most ambitious goals humankind has ever
embarked upon: a quantum computer that promises to exponentially improve
computational power for particular tasks. A number of physical systems,
spanning much of modern physics, are being developed for this task---ranging
from single particles of light to superconducting circuits---and it is not yet
clear which, if any, will ultimately prove successful. Here we describe the
latest developments for each of the leading approaches and explain what the
major challenges are for the future.Comment: 26 pages, 7 figures, 291 references. Early draft of Nature 464, 45-53
(4 March 2010). Published version is more up-to-date and has several
corrections, but is half the length with far fewer reference
Spatio-temporal Models of Lymphangiogenesis in Wound Healing
Several studies suggest that one possible cause of impaired wound healing is
failed or insufficient lymphangiogenesis, that is the formation of new
lymphatic capillaries. Although many mathematical models have been developed to
describe the formation of blood capillaries (angiogenesis), very few have been
proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a
markedly different process from angiogenesis, occurring at different times and
in response to different chemical stimuli. Two main hypotheses have been
proposed: 1) lymphatic capillaries sprout from existing interrupted ones at the
edge of the wound in analogy to the blood angiogenesis case; 2) lymphatic
endothelial cells first pool in the wound region following the lymph flow and
then, once sufficiently populated, start to form a network. Here we present two
PDE models describing lymphangiogenesis according to these two different
hypotheses. Further, we include the effect of advection due to interstitial
flow and lymph flow coming from open capillaries. The variables represent
different cell densities and growth factor concentrations, and where possible
the parameters are estimated from biological data. The models are then solved
numerically and the results are compared with the available biological
literature.Comment: 29 pages, 9 Figures, 6 Tables (39 figure files in total
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