CosMIC: a consistent metric for spike inference from calcium imaging

In recent years, the development of algorithms to detect neuronal spiking activity from two-photon calcium imaging data has received much attention. Meanwhile, few researchers have examined the metrics used to assess the similarity of detected spike trains with the ground truth. We highlight the limitations of the two most commonly used metrics, the spike train correlation and success rate, and propose an alternative, which we refer to as CosMIC. Rather than operating on the true and estimated spike trains directly, the proposed metric assesses the similarity of the pulse trains obtained from convolution of the spike trains with a smoothing pulse. The pulse width, which is derived from the statistics of the imaging data, reflects the temporal tolerance of the metric. The final metric score is the size of the commonalities of the pulse trains as a fraction of their average size. Viewed through the lens of set theory, CosMIC resembles a continuous Sørensen-Dice coefficient — an index commonly used to assess the similarity of discrete, presence/absence data. We demonstrate the ability of the proposed metric to discriminate the precision and recall of spike train estimates. Unlike the spike train correlation, which appears to reward overestimation, the proposed metric score is maximised when the correct number of spikes have been detected. Furthermore, we show that CosMIC is more sensitive to the temporal precision of estimates than the success rate

Aridification of Central Asia and uplift of the Altai and Hangay mountains, Mongolia: stable isotope evidence

Central Asia has become increasingly arid during the Cenozoic, though the mechanisms behind this aridification remain unresolved. Much attention has focused on the influence and uplift history of the Tibetan Plateau. However, the role of ranges linked to India-Asia convergence but well north of the Plateau—including the Altai, Sayan, and Hangay—in creating the arid climate of Central Asia is poorly understood. Today, these ranges create a prominent rain shadow, effectively separating the boreal forest to the north from the deserts of Central Asia. To explore the role of these mountains in modifying climate since the late Eocene, we measured carbon and oxygen stable isotopes in paleosol carbonates from three basins along a 650 km long transect at the northern edge of the Gobi Desert in Mongolia and in the lee of the Altai and Hangay mountains. We combine these data with modern air-parcel back-trajectory modeling to understand regional moisture transport pathways at each basin. In all basins, δ¹³C increases, with the largest increase in western Mongolia. The first δ¹³C increase occurs in central and southwestern Mongolia in the Oligocene. δ¹³C again increases from the upper Miocene to the Quaternary in western and southwestern Mongolia. We use a 1-D soil diffusion model to demonstrate that these δ¹³C increases are linked to declines in soil respiration driven by dramatic increases in aridity. Using modern-day empirical relations between mean annual precipitation and soil respiration, we estimate that precipitation has likely more than halved over the Neogene. Given the importance of the Hangay and Altai in steering moisture in Mongolia, we attribute these changes to differential surface uplift of the Hangay and Altai. Surface uplift in the Hangay began by the early Oligocene, blocking Siberian moisture and aridifying the northern Gobi. In contrast, surface uplift of the Altai began in the late Miocene, blocking moisture from reaching western Mongolia. Thus, the northern Gobi became increasingly arid east to west since the late Eocene, likely driven by orographic development in the Hangay during the Oligocene and the Altai in the late Miocene through Pliocene

Investigation and demonstration of dry carbon-based sorbent injection for mercury control. Quarterly technical report, October 1--December 31, 1996

The U.S. Department of Energy (DOE) has issued Public Service Company of Colorado (PSCo) a cost sharing contract to evaluate carbon-based sorbents for mercury control on a 600 acfm laboratory scale particulate control module (PCM). The PCM can simulate an electrostatic precipitator, a pulse-jet fabric filter, and a reverse air fabric filter and uses actual flue gas from an operating coal-fired power plant. Up to 3 different dry carbon-based sorbents will be tested to determine the mercury removal capability in the different configurations. The project is currently in the fifth quarter of an eight quarter Phase I project. The PCM has been fabricated and mercury removal testing with the ESP configuration has been completed. Original plans included the use on an on-line meercury analyzer to collect the test data. However, due to very low baseline mercury concentration, on-line measurement did not provide accurate data. The project has continued using a modified MESA method grab sample technique to determine inlet and outlet mercury concentrations. A major concern during sorbent evaluations has been the natural ability of the flyash at the test site to remove mercury. This has made determination of sorbent only mercury removal difficult. Overall vapor-phase mercury removals of 15 to 70% have been obtained but this includes mercury removals in the range of 30% by the flyash. It is believed that a maximum of approximately 40% removal due to the sorbent only has been obtained. A number of test and sampling modifications are in progress to increase the data confidence and many questions remain. Startup of the pulse jet configuration began in early November but results of this testing are not available at this time. The project team has decided to proceed with pulse jet testing using flue gas that does not contain significant flyash quantities to further investigate the sorbent only mercury removal

Is the Roux Limb a Determinant for Meal Size After Gastric Bypass Surgery?

The Roux-Y gastric bypass (RYGBP) is an effective weight-reducing procedure but the involved mechanisms of action are obscure. The Roux limb is the intestinal segment that following surgery is the primary recipient for food intake. The aims of the study were to explore the mechanosensory and biomechanical properties of the Roux limb and to make correlations with preferred meal size. Ten patients participated and were examined preoperatively, 6 weeks and 1 year after RYGBP. Each subject ingested unrestricted amounts of a standardized meal and the weight of the meal was recorded. On another study day, the Roux limb was subjected to gradual distension by the use of an intraluminal balloon. Luminal volume–pressure relationships and thresholds for induction of sensations were monitored. At 6 weeks and 1 year post surgery, the subjects had reduced their meal sizes by 62% and 41% (medians), respectively, compared to preoperative values. The thresholds for eliciting distension-induced sensations were strongly and negatively correlated to the preferred meal size. Intraluminal pressure during Roux limb distension, both at low and high balloon volumes, correlated negatively to the size of the meal that the patients had chosen to eat. The results suggest that the Roux limb is an important determinant for regulating food intake after Roux-Y bypass bariatric surgery

Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial

Background: Dapagliflozin reduces the risk of kidney failure and heart failure in patients with chronic kidney disease. We aimed to investigate the effects of dapagliflozin on kidney, cardiovascular, and mortality outcomes according to presence or absence of type 2 diabetes and according to underlying cause of chronic kidney disease, reported as diabetic nephropathy, chronic glomerulonephritides, ischaemic or hypertensive chronic kidney disease, or chronic kidney disease of other or unknown cause. Methods: DAPA-CKD was a multicentre, double-blind, placebo-controlled, randomised trial done at 386 study sites in 21 countries, in which participants with a urinary albumin-to-creatinine ratio of 200–5000 mg/g and an estimated glomerular filtration rate (eGFR) of 25–75 mL/min per 1·73m2 were randomly assigned (1:1) to dapagliflozin 10 mg once daily or matching placebo, as an adjunct to standard care. The primary outcome was a composite of sustained decline in eGFR of at least 50%, end-stage kidney disease, or kidney-related or cardiovascular death. Secondary efficacy outcomes were a kidney-specific composite (the same as the primary outcome but excluding cardiovascular death), a composite of cardiovascular death or hospital admission for heart failure, and all-cause mortality. In this study, we conducted a prespecified subgroup analysis of the DAPA-CKD primary and secondary endpoints by presence or absence of type 2 diabetes and by aetiology of chronic kidney disease. DAPA-CKD is registered with ClinicalTrials.gov, NCT03036150. Findings: The study took place between Feb 2, 2017, and June 12, 2020. 4304 participants were randomly assigned (2152 to dapagliflozin and 2152 to placebo) and were followed up for a median of 2·4 years (IQR 2·0–2·7). Overall, 2906 (68%) participants had a diagnosis of type 2 diabetes, of whom 396 (14%) had chronic kidney disease ascribed to causes other than diabetic nephropathy. The relative risk reduction for the primary composite outcome with dapagliflozin was consistent in participants with type 2 diabetes (hazard ratio [HR] 0·64, 95% CI 0·52–0·79) and those without diabetes (0·50, 0·35–0·72; pinteraction=0·24). Similar findings were seen for the secondary outcomes: kidney-specific composite outcome (0·57 [0·45–0·73] vs 0·51 [0·34–0·75]; Pinteraction=0·57), cardiovascular death or hospital admission for heart failure (0·70 [0·53–0·92] vs 0·79 [0·40–1·55]; Pinteraction=0·78), and all-cause mortality (0·74 [0·56–0·98] vs 0·52 [0·29–0·93]; Pinteraction=0·25). The effect of dapagliflozin on the primary outcome was also consistent among patients with diabetic nephropathy (n=2510; HR 0·63, 95% CI 0·51–0·78), glomerulonephritides (n=695; 0·43, 0·26–0·71), ischaemic or hypertensive chronic kidney disease (n=687; 0·75, 0·44–1·26), and chronic kidney disease of other or unknown cause (n=412; 0·58, 0·29–1·19; Pinteraction=0·53), with similar consistency seen across the secondary outcomes. The proportions of participants in the dapagliflozin and placebo groups who had serious adverse events or discontinued study drug due to adverse events did not vary between those with and those without type 2 diabetes. Interpretation: Dapagliflozin reduces the risks of major adverse kidney and cardiovascular events and all-cause mortality in patients with diabetic and non-diabetic chronic kidney disease

Gestational Diabetes Mellitus and Obesity

This is the sixth of a series of articles based on presentations at the America

Obesity-related cardiovascular risk factors after weight loss: a clinical trial comparing gastric bypass surgery and intensive lifestyle intervention

Objective: Weight reduction improves several obesity-related health conditions. We aimed to compare the effect of bariatric surgery and comprehensive lifestyle intervention on type 2 diabetes and obesityrelated cardiovascular risk factors. Design: One-year controlled clinical trial (ClinicalTrials.gov identifier NCT00273104). Methods: Morbidly obese subjects (19–66 years, mean (S.D.) body mass index 45.1 kg/m2 (5.6), 103 women) were treated with either Roux-en-Y gastric bypass surgery (nZ80) or intensive lifestyle intervention at a rehabilitation centre (nZ66). The dropout rate within both groups was 5%. Results: Among the 76 completers in the surgery group and the 63 completers in the lifestyle group, mean (S.D.) 1-year weight loss was 30% (8) and 8% (9) respectively. Beneficial effects on glucose metabolism, blood pressure, lipids and low-grade inflammation were observed in both groups. Remission rates of type 2 diabetes and hypertension were significantly higher in the surgery group than the lifestyle intervention group; 70 vs 33%, PZ0.027, and 49 vs 23%, PZ0.016. The improvements in glycaemic control and blood pressure were mediated by weight reduction. The surgery group experienced a significantly greater reduction in the prevalence of metabolic syndrome, albuminuria and electrocardiographic left ventricular hypertrophy than the lifestyle group. Gastrointestinal symptoms and symptomatic postprandial hypoglycaemia developed more frequently after gastric bypass surgery than after lifestyle intervention. There were no deaths. Conclusions: Type 2 diabetes and obesity-related cardiovascular risk factors were improved after both treatment strategies. However, the improvements were greatest in those patients treated with gastric bypass surgery