OBJECTIVE

To determine if the International Hypoglycaemia Study Group (IHSG) level 2 low glucose definition can identify clinically relevant hypoglycemia in clinical trials and offer value as an end point for future trials.

OBJECTIVE

To evaluate the respective contributions of short-term glycemic variability and mean daily glucose (MDG) concentration to the risk of hypoglycemia in type 1 diabetes.

OBJECTIVE

The vast number of antihyperglycemic medications and growing amount of evidence make clinical decision making difficult. The aim of this study was to investigate the safety of antihyperglycemic dual and triple therapies for type 2 diabetes management with respect to major adverse cardiovascular events, severe hypoglycemia, and all-cause mortality in a real-life clinical setting.

OBJECTIVE

We analyzed data from inpatients with diabetes admitted to a large university hospital to predict the risk of hypoglycemia through the use of machine learning algorithms.

OBJECTIVE

In patients with type 2 diabetes (T2D) and critical limb ischemia (CLI), migration of circulating CD34⁺ cells predicted cardiovascular mortality at 18 months after revascularization. This study aimed to provide long-term validation and mechanistic understanding of the biomarker.

OBJECTIVE

Despite evidence of a relationship among obstructive sleep apnea (OSA), metabolic dysregulation, and diabetes, it is uncertain whether OSA treatment can improve metabolic parameters. We sought to determine effects of long-term continuous positive airway pressure (CPAP) treatment on glycemic control and diabetes risk in patients with cardiovascular disease (CVD) and OSA.

OBJECTIVE

The aim of this study was to examine the association of circulating retinol-binding protein 4 (RBP4) levels with β-cell function across the spectrum of glucose tolerance from normal to overt type 2 diabetes.

This is what I think of as an honest cake - not tizzy, just homely, buttery and ever-so more-ish with its tender, nutty crumb and sweet, caramelised pineapple topping. I particularly love the way the sides, through some kind of magical alchemy of heat and sugar, become ever-so-slightly crunchy. There are a couple of little things I've noticed when I bake it - the first is that it cooks better and looks better when baked in a regular, not a non-stick, cake tin. And the second is that it's really important not to overload the tin with pineapple or it will release too much liquid and the centre of the cake will be soggy.

140g unsalted butter 200g dark chocolate 100g light brown sugar 100g caster sugar 2 teaspoons vanilla extract 2 eggs 1 egg yolk 85g plain flour 55g macadamia nuts, lightly toasted, chopped 30g crystallised ginger, chopped Sifted cocoa powder, to dust

I seriously love cooking on the Weber more in winter cooler temperature make us feel more cosy and accentuate the taste buds and smell . Replaced the traditional peanuts with our wonderful local macadamias

Delicious Australian dish with fresh Lilly Pilly and finger lime spritzer.

125g butter, softened 1 cup caster sugar 1 egg 1 tsp vanilla essence 1 and 1/2 cups plain flour, sifted 1 tsp baking powder 1/4 tsp. pepper leaf spice, ground 1 cup white chocolate chips 1/3 cup raw macadamia nuts, chopped

Love this time of year where our makers are abundant with the sweet aroma of fresh basil . Here is my take on a fancy potato salad of macadamia pesto , crispy prosciutto, sweet cherry tomatoes

The local lady finger bananas are so sweet and moorish!

This salad is inspired by a good chef friend of mine who cooked with me last weekend. Such a healthy way to enjoy broccoli which is so delicious at the moment. It's wonderful to utilize the whole vegetable and the added fibre in the stalk which we use in the salad.Feel free to explore with certain quantities in this recipe therefore I encourage you to taste and adjust to your own personal taste. You can also add chopped green olives which add an extra dimension.

Nothing beats beautifully roasted vegetables caramelized in their own sugar content to accompany a simple roast dinner or even on their own with a nice salad. The addition of perfumed lemon thyme and macadamia gives a nice touch.

This salad is our go-to staple. Everyone loves it. It's healthy, colourful and so, so easy. It can also be made entirely with local ingredients.

OBJECTIVE

Diabetes is a major risk factor for renal function decline and failure. The availability of multiplex panels of biochemical markers provides the opportunity to identify novel biomarkers that can better predict changes in renal function than routinely available clinical markers.

OBJECTIVE

Impaired insulin-stimulated myocardial glucose uptake has occurred in patients with type 2 diabetes with or without coronary artery disease. Whether cardiac insulin resistance is present remains uncertain in subjects at risk for type 2 diabetes, such as individuals with impaired glucose tolerance (IGT) or those with normal glucose tolerance (NGT) and 1-h postload glucose ≥155 mg/dL during an oral glucose tolerance test (NGT 1-h high). This issue was examined in this study.

OBJECTIVE

Previous studies suggested that childhood prediabetes may develop prior to obesity and be associated with relative insulin deficiency. We proposed that the insulin-deficient phenotype is genetically determined and tested this hypothesis by longitudinal modeling of insulin and glucose traits with diabetes risk genotypes in the EarlyBird cohort.

Kristen B. Campbell
Apr 1, 2004; 22:81-88
Practical Pointers

Vanessa J. Briscoe
Jul 1, 2006; 24:115-121
Feature Articles

A push to open a center devoted to research and professional development for rural K-12 holds promise for educators who work in small, isolated communities.

Chomsky, Noam -- Political and social views.

East Indians -- Australia -- Languages.

Valencia : M. Alufre, 1886.

Edinburgh : Young J. Pentland, 1895.

María F. Gil–Leyva, Ramsés H. Mena, Theodoros Nicoleris.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 1479--1507.

Abstract:
A new class of nonparametric prior distributions, termed Beta-Binomial stick-breaking process, is proposed. By allowing the underlying length random variables to be dependent through a Beta marginals Markov chain, an appealing discrete random probability measure arises. The chain’s dependence parameter controls the ordering of the stick-breaking weights, and thus tunes the model’s label-switching ability. Also, by tuning this parameter, the resulting class contains the Dirichlet process and the Geometric process priors as particular cases, which is of interest for MCMC implementations. Some properties of the model are discussed and a density estimation algorithm is proposed and tested with simulated datasets.

Zhengwei Liu, Qi Li, Fukang Zhu.

Source: Brazilian Journal of Probability and Statistics, Volume 34, Number 2, 251--272.

Abstract:
To predict time series of counts with small values and remarkable fluctuations, an available model is the $r$ states random environment process based on the negative binomial thinning operator and the geometric marginal. However, we argue that the aforementioned model may suffer from the following two drawbacks. First, under the condition of no prior information, the overdispersed property of the geometric distribution may cause the predictions fluctuate greatly. Second, because of the constraints on the model parameters, some estimated parameters are close to zero in real-data examples, which may not objectively reveal the correlation relationship. For the first drawback, an $r$ states random environment process based on the binomial thinning operator and the Poisson marginal is introduced. For the second drawback, we propose a generalized $r$ states random environment integer-valued autoregressive model based on the binomial thinning operator to model fluctuations of data. Yule–Walker and conditional maximum likelihood estimates are considered and their performances are assessed via simulation studies. Two real-data sets are conducted to illustrate the better performances of the proposed models compared with some existing models.

Bryan D. Martin, Daniela Witten, Amy D. Willis.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 94--115.

Abstract:
Using a sample from a population to estimate the proportion of the population with a certain category label is a broadly important problem. In the context of microbiome studies, this problem arises when researchers wish to use a sample from a population of microbes to estimate the population proportion of a particular taxon, known as the taxon’s relative abundance . In this paper, we propose a beta-binomial model for this task. Like existing models, our model allows for a taxon’s relative abundance to be associated with covariates of interest. However, unlike existing models, our proposal also allows for the overdispersion in the taxon’s counts to be associated with covariates of interest. We exploit this model in order to propose tests not only for differential relative abundance, but also for differential variability. The latter is particularly valuable in light of speculation that dysbiosis , the perturbation from a normal microbiome that can occur in certain disease conditions, may manifest as a loss of stability, or increase in variability, of the counts associated with each taxon. We demonstrate the performance of our proposed model using a simulation study and an application to soil microbial data.

Fangzheng Xie, Yanxun Xu.

Source: Bayesian Analysis, Volume 15, Number 1, 159--186.

Abstract:
We propose a kernel mixture of polynomials prior for Bayesian nonparametric regression. The regression function is modeled by local averages of polynomials with kernel mixture weights. We obtain the minimax-optimal contraction rate of the full posterior distribution up to a logarithmic factor by estimating metric entropies of certain function classes. Under the assumption that the degree of the polynomials is larger than the unknown smoothness level of the true function, the posterior contraction behavior can adapt to this smoothness level provided an upper bound is known. We also provide a frequentist sieve maximum likelihood estimator with a near-optimal convergence rate. We further investigate the application of the kernel mixture of polynomials to partial linear models and obtain both the near-optimal rate of contraction for the nonparametric component and the Bernstein-von Mises limit (i.e., asymptotic normality) of the parametric component. The proposed method is illustrated with numerical examples and shows superior performance in terms of computational efficiency, accuracy, and uncertainty quantification compared to the local polynomial regression, DiceKriging, and the robust Gaussian stochastic process.

Brian Neelon.

Source: Bayesian Analysis, Volume 14, Number 3, 849--875.

Abstract:
Motivated by a study examining spatiotemporal patterns in inpatient hospitalizations, we propose an efficient Bayesian approach for fitting zero-inflated negative binomial models. To facilitate posterior sampling, we introduce a set of latent variables that are represented as scale mixtures of normals, where the precision terms follow independent Pólya-Gamma distributions. Conditional on the latent variables, inference proceeds via straightforward Gibbs sampling. For fixed-effects models, our approach is comparable to existing methods. However, our model can accommodate more complex data structures, including multivariate and spatiotemporal data, settings in which current approaches often fail due to computational challenges. Using simulation studies, we highlight key features of the method and compare its performance to other estimation procedures. We apply the approach to a spatiotemporal analysis examining the number of annual inpatient admissions among United States veterans with type 2 diabetes.

Mitochondrial fission catalyzed by dynamin-related protein 1 (Drp1) is necessary for mitochondrial biogenesis and maintenance of healthy mitochondria. However, excessive fission has been associated with multiple neurodegenerative disorders, and we recently reported that mice with smaller mitochondria are sensitized to ischemic stroke injury. Although pharmacological Drp1 inhibition has been put forward as neuroprotective, the specificity and mechanism of the inhibitor used is controversial. Here, we provide genetic evidence that Drp1 inhibition is neuroprotective. Drp1 is activated by dephosphorylation of an inhibitory phosphorylation site, Ser637. We identify Bβ2, a mitochondria-localized protein phosphatase 2A (PP2A) regulatory subunit, as a neuron-specific Drp1 activator in vivo. Bβ2 KO mice of both sexes display elongated mitochondria in neurons and are protected from cerebral ischemic injury. Functionally, deletion of Bβ2 and maintained Drp1 Ser637 phosphorylation improved mitochondrial respiratory capacity, Ca²⁺ homeostasis, and attenuated superoxide production in response to ischemia and excitotoxicity in vitro and ex vivo. Last, deletion of Bβ2 rescued excessive stroke damage associated with dephosphorylation of Drp1 S637 and mitochondrial fission. These results indicate that the state of mitochondrial connectivity and PP2A/Bβ2-mediated dephosphorylation of Drp1 play a critical role in determining the severity of cerebral ischemic injury. Therefore, Bβ2 may represent a target for prophylactic neuroprotective therapy in populations at high risk of stroke.

SIGNIFICANCE STATEMENT With recent advances in clinical practice including mechanical thrombectomy up to 24 h after the ischemic event, there is resurgent interest in neuroprotective stroke therapies. In this study, we demonstrate reduced stroke damage in the brain of mice lacking the Bβ2 regulatory subunit of protein phosphatase 2A, which we have shown previously acts as a positive regulator of the mitochondrial fission enzyme dynamin-related protein 1 (Drp1). Importantly, we provide evidence that deletion of Bβ2 can rescue excessive ischemic damage in mice lacking the mitochondrial PKA scaffold AKAP1, apparently via opposing effects on Drp1 S637 phosphorylation. These results highlight reversible phosphorylation in bidirectional regulation of Drp1 activity and identify Bβ2 as a potential pharmacological target to protect the brain from stroke injury.

A previously healthy 9-year-old immigrant girl from Mexico was evaluated in the emergency department (ED) with one week of fatigue, fevers, rhinorrhea, and cough. She initially presented to her primary pediatrician, where a complete blood count revealed neutropenia, prompting referral to the ED. In the ED, she was found to be influenza A–positive. Because of dehydration, she received intravenous fluids and was admitted to the pediatric hospital medicine service. After 2 days, influenza symptoms improved, and oral intake increased. However, she was noted to have decreased bilateral lower-extremity strength, absent Achilles reflexes, decreased lower-extremity sensation and proprioception, a positive result on the Romberg sign, and abnormal heel-to-shin testing results. These findings prompted an urgent neurology consultation. After extensive imaging, laboratory evaluation, and further consultations, a diagnosis was established.

Predischarge serum or transcutaneous bilirubinometry (TcB) measurements are recommended as appropriate screening options for identifying infants at risk for neonatal hyperbilirubinemia (NH). Visual inspection for jaundice is not reliable at identifying infants with NH in the community.

When compared with visual inspection alone, coordinated TcB screening for NH in acute-care and community settings is associated with significant improvements in laboratory utilization, patient care, convenience, and safety. (Read the full article)

Approximately 1.1% to 5.9% of febrile infants aged <90 days have bacteremia, but the incidence of bacteremia in this age is unknown. Escherichia coli, group B Streptococcus, and Staphylococcus aureus are the leading causes of bacteremia.

Bacteremia occurs in 2.2% of infants who have a blood culture drawn. The incidence rate of true bacteremia was 0.57 in 1000 full-term births. The most common pathogens were Escherichia coli (56%), group B Streptococcus (21%), and Staphylococcus aureus (8%). (Read the full article)

There is a perception among clinicians that methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and/or meningitis result in a greater burden of disease than invasive infections attributed to methicillin-susceptible Staphylococcus aureus (MSSA) among very low birth weight (VLBW) infants.

VLBW infants with MRSA and MSSA bacteremia and/or meningitis have equivalent morbidity and mortality. These findings suggest that allocation of resources for prevention and treatment of both MRSA and MSSA infections among VLBW infants should be comparable. (Read the full article)

Nearly one-third of all US children are overweight or obese, with even higher prevalence among Mexican American children. Overweight and obesity increase systemic inflammation, contributing to increased risk for chronic diseases, such as type 2 diabetes mellitus and cardiovascular disease.

Obese Mexican American children had concurrent alterations in both inflammatory markers and traditional disease risk markers, relative to healthy weight children. Our results provide evidence partially explaining the health disparity for disease in Mexican American children who are overweight/obese. (Read the full article)

Isolated methylmalonic acidemia, one of the most common inborn errors of organic acid metabolism, is known to be associated with variably impaired intellectual functioning and severe biochemical and clinical abnormalities. However, the neurocognitive outcomes have yet to be fully described.

This research defines the neurocognitive phenotype of isolated methylmalonic acidemia and identifies processing speed as a specific impairment. Clinical, biochemical, and molecular genetic covariates were explored. A history of hyperammonemia at diagnosis was found to correlate with poorer cognitive outcomes. (Read the full article)

Late-onset hypocalcemia is common in neonates, often presents with seizures or tetany, and is often attributed to transient hypoparathyroidism.

Late-onset hypocalcemia in neonates is often a sign of coexisting vitamin D deficiency and hypomagnesemia and is readily managed with therapy of limited duration, and neonates presenting with tetany or seizures due to hypocalcemia are unlikely to benefit from neuroimaging studies. (Read the full article)

A dose-response relationship exists between light irradiance and decrease of total serum bilirubin concentration (TsB) at relatively low irradiances. It has been questioned whether by increasing irradiance a "saturation point" exists, above which no further decrease of TsB is seen.

We found a linear relation between light irradiance in the range of 20 to 55 μW/cm²/nm and decrease in TsB after 24 hours of therapy, with no evidence of a saturation point. (Read the full article)

The higher the predischarge bilirubin percentile reading on the hour of life–specific nomogram, the higher becomes that infant's risk of developing significant hyperbilirubinemia. Neonates in the low-risk zones (≤75th percentile) have a low risk of developing hyperbilirubinemia.

Thirty-two percent of newborns readmitted for hyperbilirubinemia had low-risk zone predischarge bilirubin percentile values, predominantly in the intermediate low-risk zone (41st–75th percentile). The intermediate low-risk zone may not be as low risk as previously thought. (Read the full article)

Although the natural course of bilirubin levels has been extensively studied in general neonatal populations, there is a paucity of data regarding bilirubin trends in neonates before the development of significant hyperbilirubinemia.

This study provides data on the natural course of transcutaneous bilirubin before the development of significant hyperbilirubinemia, and on the effect of different demographic and perinatal risk factors on the rate of bilirubin increase in neonates with borderline bilirubin values. (Read the full article)

Several meta-analyses evaluating probiotics in preterm infants suggest a beneficial effect for the prevention of necrotizing enterocolitis and death, but less for nosocomial infection. Lactobacillus reuteri may reduce these outcomes because of its immunomodulation and bactericidal properties.

Although L reuteri did not appear to decrease the rate of death or nosocomial infection, the trends suggest a protective role consistent with the literature. Feeding intolerance and duration of hospitalization were significantly decreased in premature infants ≤1500 g. (Read the full article)

It has been widely thought for the past 20 years that recurrent low blood glucose levels ≤2.5 mmol/L (45 mg/dL), even in the absence of any suggestive clinical signs, can harm a preterm infant’s long-term development.

This prospective study showed the outcome at 2 and 15 years later for the preterm infants who had a blood glucose level this low in the first 10 days of life did not differ from that of matched controls. (Read the full article)

Children with sickle cell anemia are at risk of central nervous system damage, including stroke. Even children without evidence of abnormality on neuroimaging are at risk of significant declines in neurocognitive function, starting at early ages.

This study adds the observation that poorer neurocognitive and behavioral function is associated with older age in infants and toddlers with sickle cell anemia, much earlier than previously expected. (Read the full article)

In humans, the brain growth spurt begins in the last trimester of pregnancy and extends through the first 2 years of life. Studies show poor cognitive and motor development among children who have iron deficiency anemia in infancy.

Prenatal iron deficiency anemia in the third trimester affects child mental development. Prenatal micronutrient supplementation with sufficient iron protects child mental development even when the woman’s iron deficiency anemia is not properly corrected during pregnancy. (Read the full article)

Before the introduction of conjugate pneumococcal vaccines and routine penicillin prophylaxis, febrile patients with sickle cell disease were known to have a 3% to 5% risk of bacteremia. Consequently, hospitalization rates for febrile episodes are >70%.

We observed no mortality or morbidity among those managed completely as outpatients, and bacteremia occurred in <1%. Physicians should strongly consider outpatient management of febrile children with sickle cell disease if there are no other indications for admission. (Read the full article)