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The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
In contrast to temperate regions, relationships between basin characteristics (e.g., type/size) and fossil pollen archives have received little attention in Amazonia. Here, we compare fossil pollen records of a small palm swamp (Cuatro Vientos; CV) and a nearby large lake (Laguna Chaplin, LCH) in Bolivian Amazonia, demonstrating that palm swamps can yield Quaternary pollen archives recording the history of terrestrial vegetation beyond the basin margin, rather than merely a history of localized swamp vegetation dynamics. The pollen assemblages from these two contrasting basins display remarkable agreement throughout their late Quaternary history, indicating past drier climates supported savanna landscape during the last glacial maximum (LGM; 24,000–18,000 cal yr BP) and savanna/semideciduous forest mosaic during the middle Holocene (7000-4750 cal yr BP) at both regional (inferred from LCH) and local (inferred from CV) spatial scales. Additionally, the local-scale catchment of CV and the basin's proximity to the riverine forests of the Río Paraguá enables exploration of the extent of gallery/riverine forests during the LGM and middle Holocene. We show that, between 24,000–4000 cal yr BP, riverine/gallery rainforests were substantially reduced compared with present, challenging the hypothesis that gallery rainforests were important refugia for rainforest species during the drier LGM and middle Holocene.
A single radiocarbon date derived from the Buhl burial in south-central Idaho has frequently been used as a data point for the interpretation of the Western Stemmed Tradition (WST) chronology and technology because of the stemmed biface found in situ with the human remains. AMS dating of bone collagen in 1991 produced an age of 10,675 ± 95 14C BP, immediately postdating the most widely accepted age range for Clovis. The Buhl burial has been cited as evidence that stemmed point technology may have overlapped with Clovis technology in the Intermountain West. We discuss concerns about the radiocarbon date, arguing that even at face value, the calibrated date has minimal overlap with Clovis at the 95.4% range. Furthermore, the C:N ratio of 3.69 in the analyzed collagen is outside of the typical range for well-preserved samples, indicating a postdepositional change in carbon composition, which may make the date erroneously older or younger than the age of the skeleton. Finally, the potential dietary incorporation of small amounts of anadromous fish may indicate that the burial is younger than traditionally accepted. For these reasons, we argue that the Buhl burial cannot be used as evidence of overlap between WST and Clovis.
Adverse programming of adult non-communicable disease can be induced by poor maternal nutrition during pregnancy and the periconception period has been identified as a vulnerable period. In the current study, we used a mouse maternal low-protein diet fed either for the duration of pregnancy (LPD) or exclusively during the preimplantation period (Emb-LPD) with control nutrition provided thereafter and postnatally to investigate effects on fetal bone development and quality. This model has been shown previously to induce cardiometabolic and neurological disease phenotypes in offspring. Micro 3D computed tomography examination at fetal stages Embryonic day E14.5 and E17.4, reflecting early and late stages of bone formation, demonstrated LPD treatment caused increased bone formation of relative high mineral density quality in males, but not females, at E14.5, disproportionate to fetal growth, with bone quality maintained at E17.5. In contrast, Emb-LPD caused a late increase in male fetal bone growth, proportionate to fetal growth, at E17.5, affecting central and peripheral skeleton and of reduced mineral density quality relative to controls. These altered dynamics in bone growth coincide with increased placental efficiency indicating compensatory responses to dietary treatments. Overall, our data show fetal bone formation and mineral quality is dependent upon maternal nutritional protein content and is sex-specific. In particular, we find the duration and timing of poor maternal diet to be critical in the outcomes with periconceptional protein restriction leading to male offspring with increased bone growth but of poor mineral density, thereby susceptible to later disease risk.
Recent work suggests that antihypertensive medications may be useful as repurposed treatments for mood disorders. Using large-scale linked healthcare data we investigated whether certain classes of antihypertensive, such as angiotensin antagonists (AAs) and calcium channel blockers, were associated with reduced risk of new-onset major depressive disorder (MDD) or bipolar disorder (BD).
Two cohorts of patients treated with antihypertensives were identified from Scottish prescribing (2009–2016) and hospital admission (1981–2016) records. Eligibility for cohort membership was determined by a receipt of a minimum of four prescriptions for antihypertensives within a 12-month window. One treatment cohort (n = 538 730) included patients with no previous history of mood disorder, whereas the other (n = 262 278) included those who did. Both cohorts were matched by age, sex and area deprivation to untreated comparators. Associations between antihypertensive treatment and new-onset MDD or bipolar episodes were investigated using Cox regression.
For patients without a history of mood disorder, antihypertensives were associated with increased risk of new-onset MDD. For AA monotherapy, the hazard ratio (HR) for new-onset MDD was 1.17 (95% CI 1.04–1.31). Beta blockers' association was stronger (HR 2.68; 95% CI 2.45–2.92), possibly indicating pre-existing anxiety. Some classes of antihypertensive were associated with protection against BD, particularly AAs (HR 0.46; 95% CI 0.30–0.70). For patients with a past history of mood disorders, all classes of antihypertensives were associated with increased risk of future episodes of MDD.
There was no evidence that antihypertensive medications prevented new episodes of MDD but AAs may represent a novel treatment avenue for BD.
Determining infectious cross-transmission events in healthcare settings involves manual surveillance of case clusters by infection control personnel, followed by strain typing of clinical/environmental isolates suspected in said clusters. Recent advances in genomic sequencing and cloud computing now allow for the rapid molecular typing of infecting isolates.
To facilitate rapid recognition of transmission clusters, we aimed to assess infection control surveillance using whole-genome sequencing (WGS) of microbial pathogens to identify cross-transmission events for epidemiologic review.
Clinical isolates of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, and Klebsiella pneumoniae were obtained prospectively at an academic medical center, from September 1, 2016, to September 30, 2017. Isolate genomes were sequenced, followed by single-nucleotide variant analysis; a cloud-computing platform was used for whole-genome sequence analysis and cluster identification.
Most strains of the 4 studied pathogens were unrelated, and 34 potential transmission clusters were present. The characteristics of the potential clusters were complex and likely not identifiable by traditional surveillance alone. Notably, only 1 cluster had been suspected by routine manual surveillance.
Our work supports the assertion that integration of genomic and clinical epidemiologic data can augment infection control surveillance for both the identification of cross-transmission events and the inclusion of missed and exclusion of misidentified outbreaks (ie, false alarms). The integration of clinical data is essential to prioritize suspect clusters for investigation, and for existing infections, a timely review of both the clinical and WGS results can hold promise to reduce HAIs. A richer understanding of cross-transmission events within healthcare settings will require the expansion of current surveillance approaches.
We identified a pseudo-outbreak of Mycobacterium avium in an outpatient bronchoscopy clinic following an increase in clinic procedure volume. We terminated the pseudo-outbreak by increasing the frequency of automated endoscope reprocessors (AER) filter changes from quarterly to monthly. Filter changing schedules should depend on use rather than fixed time intervals.
Second-mode wave growth within the hypersonic boundary layer of a slender cone is investigated experimentally using high-speed schlieren visualizations. Experiments were performed in AEDC Tunnel 9 over a range of unit Reynolds number conditions at a Mach number of approximately 14. A thin lens with a known density profile placed within the field of view enables calibration of the schlieren set-up, and the relatively high camera frame rates employed allow for the reconstruction of time-resolved pixel intensities at discrete streamwise locations. The calibration in conjunction with the reconstructed signals enables integrated spatial amplification rates (
factors) to be calculated for each unit Reynolds number condition and compared to
factors computed from both pressure transducer measurements and linear parabolized stability equation (PSE) solutions. Good agreement is observed between
factors computed from the schlieren measurements and those computed from the PSE solutions for the most-amplified second-mode frequencies. The streamwise development of
factors calculated from the schlieren measurements compares favourably to that calculated from the pressure measurements with slight variations in the
factor magnitudes calculated for harmonic frequencies. Finally, a bispectral analysis is carried out to identify nonlinear phase-coupled quadratic interactions present within the boundary layer. Multiple interactions are identified and revealed to be associated with the growth of disturbances at higher harmonic frequencies.
Few herbicides are available for use in lettuce and hand weeding is required for commercially acceptable weed control. More effective herbicides are needed. Here field evaluations of pendimethalin and S-metolachlor for weed control in transplanted lettuce are reported. Pendimethalin was evaluated PRE at rates between 0.6 and 6.7 kg ai ha−1, and POST at 1.1 and 2.2 kg ha−1. Both pendimethalin PRE and POST applications were safe to transplanted lettuce and provided similar weed control. Pendimethalin PRE at rates of 1.1 kg ha−1 and higher provided better weed control than the industry standard, pronamide at 1.3 kg ha−1. S-Metolachlor PRE was evaluated at rates between 0.6 and 5.6 kg ha−1. S-Metolachlor at rates up to 2.8 kg ha−1 caused little or no crop injury or yield reduction in transplanted lettuce, and S-metolachlor at rates of 1.4 kg ha−1 and higher improved weed control compared with pronamide at 1.3 kg ha−1. Pendimethalin and S-metolachlor are not labeled for transplanted lettuce, but we suggest that labeling be pursued at rates of 1.1 and 0.7 kg ha−1, respectively. Pendimethalin at 1.1 kg ha−1 applied PRE or POST improved weed control by 57 and 42%, respectively compared with pronamide. S-Metolachlor PRE at 0.7 kg ha−1 was less effective on weeds than pendimethalin, but maintained weed control level similar to pronamide. Pendimethalin and S-metolachlor have potential for use in transplanted lettuce production and provide alternatives to current transplanted lettuce herbicides.
Age-related macular degeneration (AMD) is one of the leading causes of
blindness in the developed world, with an incidence of 1:500 in patients
aged 55–64, and 1:8 in patients over 85 . Retinitis pigmentosa
(RP) is an inherited disease blinding about 1 in every 4000 individuals much
earlier in life . In both of these conditions the photoreceptor layer
degenerates, while the inner retinal neurons survive to a large extent
[3–5]. Electrically activating these neurons provides an alternative
route for visual information and raises hope for the restoration of sight to
In a normal retina, photoreceptors convert light into neural signals that are
processed by inner retinal neurons, leading to generation of action
potentials in the retinal ganglion cells (RGCs). These signals travel to the
brain through the optic nerve and serve as the basis for visual perception.
Electrical stimulation of the retina with microelectrodes can also produce
action potentials in RGCs, creating spatially patterned percepts of light
called phosphenes. Indeed, recent clinical trials with retinal prosthetic
electrode arrays have restored visual acuity to subjects blinded by retinal
degeneration up to 20/1200 using epiretinal placement (facing the
ganglion cell side) , and up to 20/550 with subretinal
implantation . While this serves as an important proof of concept with
clinically useful implications, existing retinal prosthesis designs have a
number of shortcomings.
Clostridium difficile infection (CDI) places a high burden on the US healthcare system. Recurrent CDI (RCDI) occurs frequently. Recently proposed guidelines from the American College of Gastroenterology (ACG) and the American Gastroenterology Association (AGA) include fecal microbiota transplantation (FMT) as a therapeutic option for RCDI. The purpose of this study was to estimate the cost-effectiveness of FMT compared with vancomycin for the treatment of RCDI in adults, specifically following guidelines proposed by the ACG and AGA.
We constructed a decision-analytic computer simulation using inputs from the published literature to compare the standard approach using tapered vancomycin to FMT for RCDI from the third-party payer perspective. Our effectiveness measure was quality-adjusted life years (QALYs). Because simulated patients were followed for 90 days, discounting was not necessary. One-way and probabilistic sensitivity analyses were performed.
Base-case analysis showed that FMT was less costly ($1,669 vs $3,788) and more effective (0.242 QALYs vs 0.235 QALYs) than vancomycin for RCDI. One-way sensitivity analyses showed that FMT was the dominant strategy (both less expensive and more effective) if cure rates for FMT and vancomycin were ≥70% and <91%, respectively, and if the cost of FMT was <$3,206. Probabilistic sensitivity analysis, varying all parameters simultaneously, showed that FMT was the dominant strategy over 10, 000 second-order Monte Carlo simulations.
Our results suggest that FMT may be a cost-saving intervention in managing RCDI. Implementation of FMT for RCDI may help decrease the economic burden to the healthcare system.