Hypnotic and sedative anaesthetic agents are employed during multiple medical interventions to prevent patient awareness. Careful titration of agent dosing is required to avoid negative side effects; ...the accuracy thereof may be improved by Depth of Anaesthesia Monitoring. This work investigates the potential of a patient specific depth monitoring prediction using electroencephalography recorded neural oscillation from the frontal lobe of 10 patients during sedation, where a comparison of the prediction accuracy was made across five different approaches to post‐processing; Noise Assisted‐Empirical Mode Decomposition, the Raw Signal, Linear Series Decomposition Learner, Deep Wavelet Scattering and Deep Learning features. These methods towards anaesthesia depth prediction were investigated using the Bispectral Index as ground truth, where it was seen that the Raw Signal, enhanced feature set and a low complexity classification model (Linear Discriminant Analysis) provided the best classification accuracy, in the region of 85.65 % ±10.23 % across the 10 subjects. Subsequent work in this area would now build on these results and validate the best performing methods on a wider cohort of patients, investigate means of continuous DoA estimation using regressions, and also feature optimisation exercises in order to further streamline and reduce the computation complexity of the designed model.
Summary Background By contrast with many observational studies, women in the Women's Health Initiative (WHI) trial who were randomly allocated to receive oestrogen alone had a lower incidence of ...invasive breast cancer than did those who received placebo. We aimed to assess the influence of oestrogen use on longer term breast cancer incidence and mortality in extended follow-up of this cohort. Methods Between 1993 and 1998, the WHI enrolled 10 739 postmenopausal women from 40 US clinical centres into a randomised, double-masked, placebo-controlled trial. Women aged 50–79 years who had undergone hysterectomy and had expected 3-year survival and mammography clearance were randomly allocated by a computerised, permuted block algorithm, stratified by age group and centre, to receive oral conjugated equine oestrogen (0·625 mg per day; n=5310) or matched placebo (n=5429). The trial intervention was terminated early on Feb 29, 2004, because of an adverse effect on stroke. Follow-up continued until planned termination (March 31, 2005). Consent was sought for extended surveillance from the 9786 living participants in active follow-up, of whom 7645 agreed. Using data from this extended follow-up (to Aug 14, 2009), we assessed long-term effects of oestrogen use on invasive breast cancer incidence, tumour characteristics, and mortality. We used Cox regression models to estimate hazard ratios (HRs) in the intention-to-treat population. This study is registered with ClinicalTrials.gov , number NCT00000611. Findings After a median follow-up of 11·8 years (IQR 9·1–12·9), the use of oestrogen for a median of 5·9 years (2·5–7·3) was associated with lower incidence of invasive breast cancer (151 cases, 0·27% per year) compared with placebo (199 cases, 0·35% per year; HR 0·77, 95% CI 0·62–0·95; p=0·02) with no difference (p=0·76) between intervention phase (0·79, 0·61–1·02) and post-intervention phase effects (0·75, 0·51–1·09). In subgroup analyses, we noted breast cancer risk reduction with oestrogen use was concentrated in women without benign breast disease (p=0·01) or a family history of breast cancer (p=0·02). In the oestrogen group, fewer women died from breast cancer (six deaths, 0·009% per year) compared with controls (16 deaths, 0·024% per year; HR 0·37, 95% CI 0·13–0·91; p=0·03). Fewer women in the oestrogen group died from any cause after a breast cancer diagnosis (30 deaths, 0·046% per year) than did controls (50 deaths, 0·076%; HR 0·62, 95% CI 0·39–0·97; p=0·04). Interpretation Our findings provide reassurance for women with hysterectomy seeking relief of climacteric symptoms in terms of the effects of oestrogen use for about 5 years on breast cancer incidence and mortality. However, our data do not support use of oestrogen for breast cancer risk reduction because any noted benefit probably does not apply to populations at increased risk of such cancer. Funding US National Heart, Lung, and Blood Institute; Wyeth.
Anesthetic agents are widely used for their hypnotic and sedative effects as part of surgical procedures, but despite their widespread use there continues to be suboptimal dosing of the anesthetic to ...the patients, which necessitates more effective means of monitoring the depth of anesthesia (DoA) as anesthetic agents are administered. Effective means towards DoA monitoring could improve the optimal dosing for each patient to reduce the incidence awareness under general anesthesia and post-operative cognitive dysfunction; as well as reduce the incidence of complications associated with overdosing, such as hypertension. This work presents a novel pilot case study on an ongoing research around more effective means of DoA prediction, where patient-specific models are designed using a combination of signal processing and machine learning alongside electroencephalography (EEG) signals acquired from the frontal cortex. This particular case study investigates the use of various intelligence sources, i.e., machine intelligence, representing unsupervised feature extraction from a convolutional neural network (CNN), and expert-based intelligence via handcrafted features for the prediction of the DoA. It was seen that the handcrafted features provided the highest prediction accuracy across the various patient data, due to the ability to ‘bake-in’ prior knowledge regarding the physics of the process into the feature extraction process. The highest prediction accuracy was seen to be 86.5 ± 9.9 % for the LDA classification model upon pre-processing with the Linear Series Decomposition Learner (LSDL) algorithm. The fusion of both intelligence sources also provided an equivalent prediction accuracy similar to that of the hand-crafted features only.
The anesthetic dosing procedure is a key element of safe surgical practice, where it is paramount to ensure sufficient dosing of the anesthetic agent to the patient in order to reach the desired ...depth of sedation for the necessary procedure. One means of monitoring the depth of anesthesia (DoA) involves the use of the bispectral index (BIS), which decodes electroencephalography (EEG) signals acquired from the frontal cortex in a continuous fashion. The shortcomings of this include the complexity of the decoding of EEG signals, insensitivity to certain anesthetic agents, and the costly nature of the technology, which limits its adoption in resource-constrained settings. In this paper, we investigate an alternative source of physiological measurement modalities that can track DoA sufficiently while being much more affordable. Thus, we investigate this notion with the use of the University of Queensland database, which comprises EEG-EMG-ECG physiological data from patients going through a variety of surgical procedures. As part of this, select patient datasets were utilized in addition to a variety of signal decomposition and machine learning models—which totaled around 200 simulations—in order to investigate the most optimal combination of algorithms to track DoA using different physiological measurement modalities. The results showed that under certain algorithmic combinations and modeling processes, the ECG measurement (a ubiquitous monitor in anesthetic practice) can rival and occasionally surpass the accuracy of the EEG for DoA monitoring. In addition to this, we also propose a 2-phase modeling process that involves an algorithmic selection stage followed by a model deployment stage. Subsequent work in this area is advised to involve the acquisition of more physiological data from a broader mix of patients in order to further validate the consistency of the findings made in this study.
There is growing evidence that individual bacteria sense and respond to changes in mechanical loading. However, the subtle responses of multispecies biofilms to dynamic fluid shear stress are not ...well documented because experiments often fail to disentangle any beneficial effects of shear stress from those delivered by convective transport of vital nutrients. We observed the development of biofilms with lognormally distributed microcolony sizes in drinking water on the walls of flow channels underflow regimes of increasing complexity. First, where regular vortices induced oscillating wall shear and simultaneously enhanced mass transport, which produced the thickest most extensive biofilms. Second, where unsteady uniform flow imposed an oscillating wall shear, with no enhanced transport, and where the biomass and coverage were only 20% smaller. Finally, for uniform steady flows with constant wall shear where the extent, thickness, and density of the biofilms were on average 60% smaller. Thus, the dynamics of shear stress played a significant role in promoting biofilm development, over and above its magnitude or mass transfer effects, and therefore, mechanosensing may prevail in complex multispecies biofilms which could open up new ways of controlling biofilm structure.
Individuals with “metabolically benign” obesity (obesity unaccompanied by hypertension, dyslipidemia, and diabetes) are not at elevated 10‐year risk of cardiovascular disease (CVD) compared to normal ...weight individuals. It remains unclear whether these obese individuals or normal weight individuals with clustering of cardiometabolic factors display heightened immune activity. Therefore, we characterized levels of acute‐phase reactants (C‐reactive protein (CRP), interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), white blood cell (WBC) count), adhesion molecules (E‐selectin, vascular cell adhesion molecule‐1), and coagulation products (fibrinogen, plasminogen activator inhibitor‐1 (PAI‐1)) among four body size phenotypes (normal weight with 0/1 vs. ≥2 metabolic syndrome components/diabetes and overweight/obesity with 0/1 vs. ≥2 metabolic syndrome components/diabetes) in cross‐sectional analyses of 1,889 postmenopausal women from the Women's Health Initiative Observational Study (WHI‐OS) nested case–control stroke study. Higher levels of all three inflammatory marker categories were found among women with overweight/obesity or ≥2 metabolic syndrome components or diabetes. Compared to normal weight women with 0 or 1 metabolic syndrome components, normal weight women with ≥2 metabolic syndrome components or diabetes were more likely to have ≥3 inflammatory markers in the top quartile (multivariate odds ratio (OR) 2.0, 95% confidence interval (CI): 1.3–3.0), as were overweight/obese women with 0 or 1 metabolic syndrome components (OR 2.3; 95% CI: 1.5–3.5). Overweight/obese women with ≥2 metabolic syndrome components or diabetes had the highest OR (OR 4.2; 95% CI: 2.9–5.9). Despite findings that metabolically benign obese individuals are not at increased 10‐year risk of CVD compared to normal weight individuals, the current results suggest that overweight/obese women without clustering of cardiometabolic risk factors still possess abnormal levels of inflammatory markers.
OBJECTIVE:--Experimental and epidemiologic studies suggest that calcium and vitamin D may reduce the risk of developing diabetes. We examined the effect of calcium plus vitamin D supplementation on ...the incidence of drug-treated diabetes in postmenopausal women. RESEARCH DESIGN AND METHODS--The Women's Health Initiative Calcium/Vitamin D Trial randomly assigned postmenopausal women to receive 1,000 mg elemental calcium plus 400 IU of vitamin D3 daily, or placebo, in a double-blind fashion. Among 33,951 participants without self-reported diabetes at baseline, we ascertained by treatment assignment new diagnoses of diabetes treated with oral hypoglycemic agents or insulin. Effects of the intervention on fasting measurements of glucose, insulin, and insulin resistance were examined among a subset of participants. RESULTS:--Over a median follow-up time of 7 years, 2,291 women were newly diagnosed with diabetes. The hazard ratio for incident diabetes associated with calcium/vitamin D treatment was 1.01 (95% CI 0.94-1.10) based on intention to treat. This null result was robust in subgroup analyses, efficacy analyses accounting for nonadherence, and analyses examining change in laboratory measurements. CONCLUSIONS:--Calcium plus vitamin D3 supplementation did not reduce the risk of developing diabetes over 7 years of follow-up in this randomized placebo-controlled trial. Higher doses of vitamin D may be required to affect diabetes risk, and/or associations of calcium and vitamin D intake with improved glucose metabolism observed in nonrandomized studies may be the result of confounding or of other components of foods containing these nutrients.
Methanogenic sludge granules are densely packed, small, spherical biofilms found in anaerobic digesters used to treat industrial wastewaters, where they underpin efficient organic waste conversion ...and biogas production. Each granule theoretically houses representative microorganisms from all of the trophic groups implicated in the successive and interdependent reactions of the anaerobic digestion (AD) process. Information on exactly how methanogenic granules develop, and their eventual fate will be important for precision management of environmental biotechnologies. Granules from a full-scale bioreactor were size-separated into small (0.6-1 mm), medium (1-1.4 mm), and large (1.4-1.8 mm) size fractions. Twelve laboratory-scale bioreactors were operated using either small, medium, or large granules, or unfractionated sludge. After >50 days of operation, the granule size distribution in each of the small, medium, and large bioreactor sets had diversified beyond-to both bigger and smaller than-the size fraction used for inoculation. Interestingly, extra-small (XS; <0.6 mm) granules were observed, and retained in all of the bioreactors, suggesting the continuous nature of granulation, and/or the breakage of larger granules into XS bits. Moreover, evidence suggested that even granules with small diameters could break. "New" granules from each emerging size were analyzed by studying community structure based on high-throughput 16S rRNA gene sequencing.
,
,
, and
represented the majority of the community in new granules. H2-using, and not acetoclastic, methanogens appeared more important, and were associated with abundant syntrophic bacteria. Multivariate integration (MINT) analyses identified distinct discriminant taxa responsible for shaping the microbial communities in different-sized granules.
Experimental and epidemiological studies suggest that calcium and vitamin D supplements may lower blood pressure. We examined the effect of calcium plus vitamin D supplementation on blood pressure ...and the incidence of hypertension in postmenopausal women. The Womenʼs Health Initiative Calcium/Vitamin D Trial randomly assigned 36 282 postmenopausal women to receive 1000 mg of elemental calcium plus 400 IU of vitamin D3 daily or placebo in a double-blind fashion. Change in blood pressure and the incidence of hypertension were ascertained. Over a median follow-up time of 7 years, there was no significant difference in the mean change over time in systolic blood pressure (0.22 mm Hg; 95% CI−0.05 to 0.49 mm Hg) and diastolic blood pressure (0.11 mm Hg; 95% CI−0.04 to 0.27 mm Hg) between the active and placebo treatment groups. This null result was robust in analyses accounting for nonadherence to study pills and in baseline subgroups of interest, including black subjects and women with hypertension or high levels of blood pressure, with low intakes of calcium and vitamin D or low serum levels of vitamin D. In 17 122 nonhypertensive participants at baseline, the hazard ratio for incident hypertension associated with calcium/vitamin D treatment was 1.01 (95% CI0.96 to 1.06.) In postmenopausal women, calcium plus vitamin D3 supplementation did not reduce either blood pressure or the risk of developing hypertension over 7 years of follow-up.
Bdellovibrio bacteriovorus is a predatory, Gram-negative bacteria that feeds on many pathogenic bacteria and has been investigated as a possible solution for mitigating biofilms in different fields. ...The application depends on more fundamental ecological studies into the dynamics between
and their prey. To do so requires an accurate, reliable, and, preferably rapid, way of enumerating the cells. Flow cytometry (FCM) is potentially a rapid, accurate, and inexpensive tool for this, but it has yet to be validated in the enumeration of
. In this study, we developed a protocol to measure the number of
in samples of various densities using FCM and compared the results with those of other methods: optical density (OD), PFU assay (PFU), and quantitative PCR (qPCR). We observed a strong correlation between values obtained using FCM and PFU (ρ = 0.923) and FCM and qPCR (ρ = 0.987). Compared to optical density there was a much weaker correlation (ρ = 0.784), which was to be expected given the well-documented uncertainty in converting optical density (OD) to cell numbers. The FCM protocol was further validated by demonstrating its ability to distinguish and count mixed populations of
and the prey Pseudomonas. Thus, the accuracy of FCM as well as its speed and reproducibility make it a suitable alternative for measuring
cell numbers, especially where many samples are required to capture the dynamics of predator-prey interactions.
The rise of antibiotic resistance and the unwanted growth of bacteria is a universally growing problem. Predatory bacteria can be used as a biological alternative to antibiotics because they grow by feeding on other bacteria. To apply this effectively requires further study and a deeper understanding of the forces that drive a prey population to elimination. Initially, such studies require more reliable methods to count these cells. Flow cytometry (FCM) is potentially a rapid, accurate, and inexpensive tool for this, but it has yet to be validated for predatory bacteria. This study develops a protocol to count the predatory bacteria Bdellovibrio bacteriovorus and its Pseudomonas prey using FCM and compare the results with those of other methods, demonstrating its ability for studies into B. bacteriovorus predation dynamics. This could lead to the use of B. bacteriovorus for killing bacterial biofilms in fields, such as drinking water and agriculture.
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