Emergence of multi-body interactions in a fermionic lattice clock.

Alkaline-earth atoms have metastable 'clock' states with minute-long optical lifetimes, high-spin nuclei and SU(N)-symmetric interactions, making them powerful platforms for atomic clocks1, quantum information processing2 and quantum simulation3. Few-particle systems of such atoms provide opportunities to observe the emergence of complex many-body phenomena with increasing system size4. Multi-body interactions among particles are emergent phenomena, which cannot be broken down into sums over underlying pairwise interactions. They could potentially be used to create exotic states of quantum matter5,6, but have yet to be explored in ultracold fermions. Here we create arrays of isolated few-body systems in an optical clock based on a three-dimensional lattice of fermionic 87Sr atoms. We use high-resolution clock spectroscopy to directly observe the onset of elastic and inelastic multi-body interactions among atoms. We measure the frequency shifts of the clock transition for varying numbers of atoms per lattice site, from n = 1 to n = 5, and observe nonlinear interaction shifts characteristic of elastic multi-body effects. These measurements, combined with theory, elucidate an emergence of SU(N)-symmetric multi-body interactions, which are unique to fermionic alkaline-earth atoms. To study inelastic multi-body effects, we use these frequency shifts to isolate n-occupied sites in the lattice and measure the corresponding lifetimes of the clock states. This allows us to access the short-range few-body physics without experiencing the systematic effects that are encountered in a bulk gas. The lifetimes that we measure in the isolated few-body systems agree very well with numerical predictions based on a simple model for the interatomic potential, suggesting a universality in ultracold collisions. By connecting these few-body systems through tunnelling, the favourable energy and timescales of the interactions will allow our system to be used for studies of high-spin quantum magnetism7,8 and the Kondo effect3,9.

Dipole-Dipole Frequency Shifts in Multilevel Atoms.

Dipole-dipole interactions lead to frequency shifts that are expected to limit the performance of next-generation atomic clocks. In this work, we compute dipolar frequency shifts accounting for the intrinsic atomic multilevel structure in standard Ramsey spectroscopy. When interrogating the transitions featuring the smallest Clebsch-Gordan coefficients, we find that a simplified two-level treatment becomes inappropriate, even in the presence of large Zeeman shifts. For these cases, we show a net suppression of dipolar frequency shifts and the emergence of dominant nonclassical effects for experimentally relevant parameters. Our findings are pertinent to current generations of optical lattice and optical tweezer clocks, opening a way to further increase their current accuracy, and thus their potential to probe fundamental and many-body physics.

Preoperative neutrophil:lymphocyte and platelet:lymphocyte ratios predict endometrial cancer survival.

BACKGROUND: Variations in systemic inflammatory response biomarker levels have been associated with adverse clinical outcome in various malignancies. This study determined the prognostic significance of preoperative neutrophil:lymphocyte (NLR), platelet:lymphocyte (PLR) and monocyte:lymphocyte (MLR) ratios in endometrial cancer. METHODS: Clinicopathological and 5-year follow-up data were obtained for a retrospective series of surgically treated endometrial cancer patients (n=605). Prognostic significance was determined for overall (OS) and cancer-specific survival (CSS) using Cox proportional hazards models and Kaplan-Meier analysis. Receiver-operator characteristic and log-rank functions were used to optimise cut-offs. NLR, PLR and MLR associations with clinicopathological variables were determined using non-parametric tests. RESULTS: Applying cut-offs of ⩾2.4 (NLR), ⩾240 (PLR) and ⩾0.19 (MLR), NLR and PLR (but not MLR) had independent prognostic significance. Combining NLR and PLR scores stratified patients into low (NLR-low and PLR-low), intermediate (NLR-high or PLR-high) and high risk (NLR-high and PLR-high) groups: multivariable hazard ratio (HR) 2.51; P<0.001 (OS); HR 2.26; P<0.01 (CSS) for high vs low risk patients. Increased NLR and PLR were most strongly associated with advanced stage (P<0.001), whereas increased MLR was strongly associated with older age (P<0.001). CONCLUSION: Both NLR and PLR are independent prognostic indicators for endometrial cancer, which can be combined to provide additional patient stratification.

Severe sepsis in the emergency department - an observational cohort study from the university hospital of the West Indies.

OBJECTIVE: To describe the incidence, treatment and outcomes of patients with severe sepsis and septic shock in a setting where early goal directed therapy (EGDT) is not routinely performed. METHOD: An observational study of all adult patients admitted from the emergency department (ED) of the University Hospital of the West Indies (UHWI) with a diagnosis of severe sepsis and septic shock from July 5, 2007 to September 1, 2008 was conducted. Baseline parameters, treatment patterns and in-hospital outcomes were evaluated. RESULTS: A total of 58 011 patients were seen and 762 (1.3%) had sepsis, 117 (15.4%) of whom were classified as severe sepsis or septic shock. Mean (SD) age was 59.2 (23.3) years and 49% were female. Medical history included hypertension (29%), diabetes mellitus (26%), stroke (8%), heart failure (6%) and HIV (6%). The most common sources of sepsis were pneumonia (67%) and urinary tract infection (46%). Median, interquartile range (IQR) time from triage to antibiotic administration was 126 (88, 220) minutes and antibiotics were given to 65.7% within three hours. Overall, organisms were sensitive to empirical antibiotics in 69%. Median (IQR) lactate was 5.3 (4.5, 7.5) mmol/L. Most patients (95%) were admitted to the ward; 1% went to the intensive care unit (ICU) and 2% died in the ED. Mean (SD) length of hospital stay was 9.5 (10.3) days. In-hospital mortality was 25% and survival correlated inversely with age (rpb = -0.25; p = 0.006). CONCLUSION: Despite a lack of EGDT, sepsis treatment patterns were consistent with "best-practice" and mortality was lower than international comparators.

Health impact of research in emergency medicine--moving forward in the field.

This article provides a brief description of the conceptual framework of some specific areas of research carried out either collaboratively or independently in the Emergency Department in an effort to positively impact on health issues in an era of evidence-based medicine. The paper focusses on epidemiological studies of infectious diseases, chronic non-communicable diseases, and a recent update on trauma patterns. Conduction of clinical trials is also highlighted. The role of collaboration in Emergency medicine is also discussed. Research must be developed deliberately to facilitate the primary goal of improved patient care and outcomes. Further recommendations are suggested.

ASPM and microcephalin expression in epithelial ovarian cancer correlates with tumour grade and survival.

BACKGROUND: The clinico-pathological and molecular heterogeneity of epithelial ovarian cancer (EOC) complicates its early diagnosis and successful treatment. Highly aneuploid tumours and the presence of ascitic fluids are hallmarks of EOC. Two microcephaly-associated proteins, abnormal spindle-like microcephaly-associated protein (ASPM) and microcephalin, are involved in mitosis and DNA damage repair. Their expression is deregulated at the RNA level in EOC. Here, ASPM and microcephalin protein expression in primary cultures established from the ascites of patients with EOC was determined and correlated with clinical data to assess their suitability as biomarkers. METHODS: Five established ovarian cancer cell lines, cells derived from two benign ovarian ascites samples and 40 primary cultures of EOC derived from ovarian ascites samples were analysed by protein slot blotting and/or immunofluorescence to determine ASPM and microcephalin protein levels and their cellular localisation. Results were correlated with clinico-pathological data. RESULTS: A statistically significant correlation was identified for ASPM localisation and tumour grade, with high levels of cytoplasmic ASPM correlating with grade 1 tumours. Conversely, cytoplasmic microcephalin was only identified in high-grade tumours. Furthermore, low levels of nuclear microcephalin correlated with reduced patient survival. CONCLUSION: Our results suggest that ASPM and microcephalin have the potential to be biomarkers in ovarian cancer.

Comparison of pegvisomant and long-acting octreotide in patients with acromegaly naïve to radiation and medical therapy.

BACKGROUND: Normalization of IGF-I in patients with acromegaly is associated with a decrease in mortality. Pegvisomant may be more effective in lowering IGF-I than octreotide. SUBJECTS AND METHODS: The efficacy and safety of pegvisomant and octreotide long-acting release (LAR) were compared in 118 patients with acromegaly in this 52-week, multicenter, open-label, randomized study. The primary endpoint was IGF-I normalization at week 52. Secondary endpoints included mean changes from baseline in IGF-I, IGF binding protein 3, acromegaly signs and symptom scores, ring size, acromegaly quality of life questionnaire scores, and safety. RESULTS: Fifty-six patients received pegvisomant and 57 received octreotide LAR. IGF-I normalized in 51% of pegvisomant patients and 34% treated with octreotide LAR (p=0.09, ns). Patients with baseline IGF-I > or = 2x upper limit of normal had a higher rate of IGF-I normalization with pegvisomant vs octreotide LAR (p=0.05). Among the patients who did not achieve a normalized IGF-I, pegvisomant-treated patients were more likely to be receiving < 30 mg of study drug (71% vs 16%). Treatment-related adverse events were mild-to-moderate in both groups. Mean fasting glucose decreased in diabetic and non-diabetic patients on pegvisomant whereas octreotide LAR was associated with an increase at week 52 (p=0.005 and p=0.003 between groups, respectively). Mean change in tumor volume during treatment was similar between groups. CONCLUSIONS: Pegvisomant and octreotide LAR were equally effective in normalizing IGF-I in the overall population, and pegvisomant was more effective in patients with higher baseline IGF-I levels. Pegvisomant had a more favorable effect on parameters of glycemic control.

Delays in presentations of stroke patients at the University Hospital of the West Indies.

Thrombolytic therapy has been proven to be beneficial in selected patients with ischaemic strokes. Early diagnosis is paramount because there is a narrow therapeutic window for these patients to derive benefit from thrombolytics. We sought to evaluate the timing of stroke presentations at the University Hospital of the West Indies (UHWI) in order to assess the potential eligibility for definitive therapy A retrospective audit of all consecutive patients who had emergent computed tomographic (CT) scans for suspected ischaemic stroke at the UHWI was performed over a six-month period between February 2006 and July 2006. Data were extracted from the hospital records and analysed using SPSS version 12. There were 331 patients evaluated with brain CT for a clinically suspected stroke during the study period. Complete time documentation and CT scans were available for analysis in 171 patients with ischaemic strokes. The average age was 64.5 years (range +/- SD: 3-98 +/- 19.9 years) with a slight male preponderance (58% vs. 42%). There was considerable pre-hospital delay with 63% of patients presenting more than 12 hours after the onset of symptoms. There were also long inhospital delays. Only 52% of patients were assessed by a physician within an hour of presentation to hospital and only 55% of patients had CT scans completed within three hours of a physician s request. Although thrombolysis is not routinely performed for ischaemic strokes at our institution, sensitization of physicians and the general public in our setting to symptoms and signs of this disease is urgently needed to improve stroke management, whereby definitive treatment can be considered for selected patients.

Abnormal connectivity in the posterior cingulate and hippocampus in early Alzheimer's disease and mild cognitive impairment.

BACKGROUND: Brain imaging studies of early Alzheimer's disease (AD) have shown decreased metabolism predominantly in the posterior cingulate cortex (PCC), medial temporal lobe, and inferior parietal lobe. This study investigated functional connectivity between these regions, as well as connectivity between these regions and the whole brain. METHODS: Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) studies were performed in subjects with early AD, mild cognitive impairment (MCI), and normal controls. RESULTS: The data indicate both decreased fiber connections and disrupted connectivity between the hippocampus and PCC in early AD. The MCI group showed reduced fiber numbers derived from PCC and hippocampus to the whole brain. CONCLUSIONS: The fMRI and DTI results confirmed decreased connectivity from both the PCC and hippocampus to the whole brain in MCI and AD and reduction in connectivity between these two regions, which plausibly represents an early imaging biomarker for AD.

The evolution of emergency medicine in Jamaica.

Emergency Medicine in Jamaica has evolved rapidly over the past 20 years and has gained recognition as a specialty. A residency training programme has been established, trademark life support courses are now available, moves to develop areas of sub-specialization have begun and an emergency medicine association has been formed. There has been an increase in the diagnostic modalities in the main teaching institution, the University Hospital of the West Indies (UHWI). There is an urgent need for improvements in pre-hospital care. This will require the development of an efficient Emergency Medical Service (EMS). More emphasis and attention is required on disaster medicine, toxicology and trauma. Increased training of emergency physicians and nurses, advances in academia and research, and greater advocacy by local emergency physicians will further advance the specialty.

Machine Learning in Radiology: Applications Beyond Image Interpretation.

Much attention has been given to machine learning and its perceived impact in radiology, particularly in light of recent success with image classification in international competitions. However, machine learning is likely to impact radiology outside of image interpretation long before a fully functional "machine radiologist" is implemented in practice. Here, we describe an overview of machine learning, its application to radiology and other domains, and many cases of use that do not involve image interpretation. We hope that better understanding of these potential applications will help radiology practices prepare for the future and realize performance improvement and efficiency gains.

A Fermi-degenerate three-dimensional optical lattice clock.

Strontium optical lattice clocks have the potential to simultaneously interrogate millions of atoms with a high spectroscopic quality factor of 4 × 1017 Previously, atomic interactions have forced a compromise between clock stability, which benefits from a large number of atoms, and accuracy, which suffers from density-dependent frequency shifts. Here we demonstrate a scalable solution that takes advantage of the high, correlated density of a degenerate Fermi gas in a three-dimensional (3D) optical lattice to guard against on-site interaction shifts. We show that contact interactions are resolved so that their contribution to clock shifts is orders of magnitude lower than in previous experiments. A synchronous clock comparison between two regions of the 3D lattice yields a measurement precision of 5 × 10-19 in 1 hour of averaging time.

Eukaryotic gene expression: metabolite control by amino acids.

Our understanding of the metabolite control in mammalian cells lags far behind that in prokaryotes. This is particularly true for amino-acid-dependent gene expression. Few proteins have been identified for which synthesis is selectively regulated by amino-acid availability, and the mechanisms for control of transcription and translation in response to changes in amino-acid availability have not yet been elucidated. The intimate relationship between amino-acid supply and the fundamental cellular process of protein synthesis makes amino-acid-dependent control of gene expression particularly important. Future studies should provide important insight into amino-acid and other nutrient signaling pathways, and their impact on cellular growth and metabolism.

Improved Survival from Ovarian Cancer in Patients Treated in Phase III Trial Active Cancer Centres in the UK.

AIMS: Ovarian cancer is the principal cause of gynaecological cancer death in developed countries, yet overall survival in the UK has been reported as being inferior to that in some Western countries. As there is a range of survival across the UK we hypothesised that in major regional centres, outcomes are equivalent to the best internationally. MATERIALS AND METHODS: Data from patients treated in multicentre international and UK-based trials were obtained from three regional cancer centres in the UK; Manchester, University College London and Leeds (MUL). The median progression-free survival (PFS) and overall survival were calculated for each trial and compared with the published trial data. Normalised median survival values and the respective 95% confidence intervals (ratio of pooled MUL data to trial median survival) were calculated to allow inter-trial survival comparisons. This strategy then allowed a comparison of median survival across the UK, in three regional UK centres and in international centres. RESULTS: The analysis showed that the trial-reported PFS was the same in the UK, in the MUL centres and in international centres for each of the trials included in the study. Overall survival was, however, 45% better in major regional centre-treated patients (95% confidence interval 9-73%) than the median overall survival reported in UK trials, whereas the median overall survival in MUL centres equated with that achieved in international centres. CONCLUSION: The data suggest that international survival statistics are achieved in UK regional cancer centres.

Systematic evaluation of an atomic clock at 2 × 10(-18) total uncertainty.

The pursuit of better atomic clocks has advanced many research areas, providing better quantum state control, new insights in quantum science, tighter limits on fundamental constant variation and improved tests of relativity. The record for the best stability and accuracy is currently held by optical lattice clocks. Here we take an important step towards realizing the full potential of a many-particle clock with a state-of-the-art stable laser. Our (87)Sr optical lattice clock now achieves fractional stability of 2.2 × 10(-16) at 1 s. With this improved stability, we perform a new accuracy evaluation of our clock, reducing many systematic uncertainties that limited our previous measurements, such as those in the lattice ac Stark shift, the atoms' thermal environment and the atomic response to room-temperature blackbody radiation. Our combined measurements have reduced the total uncertainty of the JILA Sr clock to 2.1 × 10(-18) in fractional frequency units.

Genetic interrelationships of saccharolytic Clostridium botulinum types B, E and F and related clostridia as revealed by small-subunit rRNA gene sequences.

The phylogenetic interrelationships of saccharolytic C. botulinum types B, E and F together with eleven other saccharolytic clostridia were examined by 16S rRNA gene sequencing. Comparative analysis of the sequence data revealed that the saccharolytic C. botulinum types B, E and F were highly related and represent a single genetic group. Strains of C. barati and C. butyricum that produce botulinal neurotoxin revealed almost 100% 16S rRNA sequence identity with their respective non-toxigenic counterparts and were phylogenetically distinct from saccharolytic C. botulinum (types B, E and F). Proteolytic C. botulinum type F was shown to be phylogenetically remote from the saccharolytic C. botulinum group. The implications of the sequence data for the taxonomy of the C. botulinum complex are discussed.

Towards a phylogeny of the clostridia based on 16S rRNA sequences.

The 16S rRNA sequences of 17 species of the genus Clostridium were determined by direct sequencing of their PCR amplified genes. The sequences were aligned with those from other known clostridial species and representative low G + C Gram-positive relatives, and a phylogenetic tree was constructed. It was evident from the comparative sequence analysis that the genus Clostridium as presently constituted is phylogenetically extremely heterogeneous. This study corroborates and extends earlier findings in showing that many non-sporeforming bacteria are phylogenetically closely intermixed with Clostridium species. The taxonomic implications of the phylogenetic findings are discussed.

Corynebacterium lipophiloflavum sp. nov. isolated from a patient with bacterial vaginosis.

A unique coryneform bacterium was isolated from a patient with bacterial vaginosis. Chemotaxonomical investigations demonstrated that the unknown bacterium belonged to the genus Corynebacterium. The yellow-pigmented, slightly lipophilic, oxidative, urea-hydrolyzing bacterium could be phenotypically readily differentiated from the other members of the genus Corynebacterium. Comparative 16S rRNA gene analysis revealed that the bacterium represented a new subline within the genus Corynebacterium for which the name Corynebacterium lipophiloflavum sp. nov. is proposed. The type strain is CCUG 37336 (DSM 44291).