An order-theoretic perspective on modes and maximum a posteriori estimation in Bayesian inverse problems

It is often desirable to summarise a probability measure on a space $X$ in terms of a mode, or MAP estimator, i.e.\ a point of maximum probability. Such points can be rigorously defined using masses of metric balls in the small-radius limit. However, the theory is not entirely straightforward: the literature contains multiple notions of mode and various examples of pathological measures that have no mode in any sense. Since the masses of balls induce natural orderings on the points of $X$, this article aims to shed light on some of the problems in non-parametric MAP estimation by taking an order-theoretic perspective, which appears to be a new one in the inverse problems community. This point of view opens up attractive proof strategies based upon the Cantor and Kuratowski intersection theorems; it also reveals that many of the pathologies arise from the distinction between greatest and maximal elements of an order, and from the existence of incomparable elements of $X$, which we show can be dense in $X$, even for an absolutely continuous measure on $X = \mathbb{R}$.Comment: 38 page

Reduced levels of two modifiers of epigenetic gene silencing, Dnmt3a and Trim28, cause increased phenotypic noise

Background: Inbred individuals reared in controlled environments display considerable variance in many complex traits but the underlying cause of this intangible variation has been an enigma. Here we show that two modifiers of epigenetic gene silencing play a critical role in the process.Results: Inbred mice heterozygous for a null mutation in DNA methyltransferase 3a (Dnmt3a) or tripartite motif protein 28 (Trim28) show greater coefficients of variance in body weight than their wild-type littermates. Trim28 mutants additionally develop metabolic syndrome and abnormal behavior with incomplete penetrance. Genome-wide gene expression analyses identified 284 significantly dysregulated genes in Trim28 heterozygote mutants compared to wild-type mice, with Mas1, which encodes a G-protein coupled receptor implicated in lipid metabolism, showing the greatest average change in expression (7.8-fold higher in mutants). This gene also showed highly variable expression between mutant individuals.Conclusions: These studies provide a molecular explanation of developmental noise in whole organisms and suggest that faithful epigenetic control of transcription is central to suppressing deleterious levels of phenotypic variation. These findings have broad implications for understanding the mechanisms underlying sporadic and complex disease in humans

Second-layer polysilicon structures for gate end-around leakage-current compensation in bulk CMOS ICs

CMOS integrated circuits (ICs) operating in space or other radiation environments can suffer from three different reliability problems due to the radiation: total dose effects, dose rate effects, and single event effects. The two most significant total-dose reliability problems are subthreshold, gat, end-around leakage current and threshold voltage shift. This article documents the theory, design, implementation, and testing of new, second-layer polysilicon structures that can compensate for radiation-induced, subthreshold, gate, end-around, leakage current. Second-layer polysilicon is available in many commercial, bulk CMOS processes and is normally used for floating-gate devices, such as EEPROMs and FPLAs, and charge-coupled devices such as CCD focal plan arrays. The use of the described structures in CMOS ICs would allow radiation tolerant ICs to be fabricated with commercial, bulk CMOS processors, greatly reducing manufacturing costs when compared to the cost of fabricating ICs on dedicated, radiation-hardened process lines

Phaeochromocytoma in pregnancy: timing of surgery, mode of delivery and magnesium

Phaeochromocytoma in pregnancy is rare. It is associated with high rates of fetal and maternal mortality especially in undiagnosed cases. There are no reliable data comparing outcomes regarding the timing of removal of tumour, or comparing outcomes between vaginal and caesarean delivery. Management should be individualized based upon consultation between the mother, obstetrician, anaesthetist, surgeon and physician. Magnesium infusion should be considered peripartum and/or at the timing of tumour resection

Efficient diagnosis of ratoon stunting disease of sugarcane by quantitative PCR on pooled leaf sheath biopsies

Ratoon stunting disease (RSD), caused by the bacterium Leifsonia xyli subsp. xyli, is arguably one of the most devastating diseases of sugarcane. Four diagnostic techniques were compared for 100 fields of sugarcane (Saccharum interspecific hybrids) of unknown infection status. These were quantitative polymerase chain reaction on pooled leaf sheath biopsies (LSB-qPCR), conventional PCR on the same templates (LSB-PCR), evaporative-binding immunoassay (EB-EIA) coupled with phase contrast microscopy (PCM) on expressed xylem sap from the same fields, and conventional PCR on the same xylem sap samples. LSB-qPCR and LSB-PCR detected the causal agent in 27 and 18 fields respectively, while from samples of expressed xylem sap from the same fields, conventional PCR identified 12 infections, and EB-EIA/PCM detected L. xyli subsp. xyli in 3 fields. The sensitivities of qPCR and PCR were approximately 103 CFU ml-1 and 104 CFU ml-1 respectively, determined from plate counts of a dilution series. Tests were conducted on a further 139 LSB samples from across the Australian industry, with qPCR and PCR diagnosing RSD in 31 and 25 fields respectively. Using qPCR and PCR on LSB samples, RSD was diagnosed in a range of cultivars throughout the year, and could detect L. xyli subsp. xyli in sugarcane ranging from 3 months to greater than 1 year old

The Cost-Effectiveness of Clinic-Based Chloral Hydrate Sedation versus General Anaesthesia for Paediatric Ophthalmological Procedures

Produced by Technology Assessment at SickKids, Hospital for Sick Children.The primary objective was to determine the incremental cost of paediatric eye examinations carried out in the clinic under sedation using oral chloral hydrate compared to examinations carried out in the OR using general anesthesia (GA) per additional successful procedure gained from a societal perspective. The secondary objective was to conduct a cost-minimization analysis (CMA) under assumptions of equivalent effectiveness between clinic-based sedation and GA.Supported by Brandan's Eye Research Fund

Compounds from Geijera parviflora with prostaglandin E2 inhibitory activity may explain its traditional use for pain relief

Ethnopharmacological relevance: Australian Aboriginal people used crushed leaves of Geijera parviflora Lindl. both internally and externally for pain relief, including for toothache ( Cribb and Cribb, 1981). This study tested the hypothesis that this traditional use might be at least in part explained by the presence of compounds with anti-inflammatory activity.Materials and methods: A crude extract (95% EtOH) was prepared from powdered dried leaves. From the CH3Cl fraction of this extract compounds were isolated by bioassay-guided fractionation and tested for: (1) cytotoxicity in RAW 264.7 murine leukemic monocyte–macrophages, (2) prostaglandin E2 (PGE2) inhibitory activity in 3T3 Swiss albino mouse embryonic fibroblast cells, as well as (3) nitric oxide (NO) and (4) tumour necrosis factor alpha (TNFα) inhibitory activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Isolated compounds were also tested for (5) antibacterial activity against a panel of Gram-positive (Staphylococcus aureus ATCC 29213 and ATCC 25923, Staphylococcusepidermidis ATCC 35984, biofilm-forming) and Gram-negative (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853) strains by broth microdilution. Results: Eleven compounds were isolated, including one new flavone and one new natural product, with a further four compounds reported from this species for the first time. Some of the compounds showed good anti-inflammatory activity in vitro. In particular, flindersine (1) and N-(acetoxymethyl) flindersine (3) inhibited PGE2 release with IC50values of 5.0 μM and 4.9 μM, respectively, without any significant cytotoxicity. Several other compounds showed moderate inhibition of NO (5, 6, 7) and TNF-α (6), with IC50 in the low micromolar range; however much of this apparent activity could be accounted for by the cytotoxicity of these compounds. None of the compounds showed anti-bacterial activity. Conclusions: The inhibition of PGE2, an important mediator of inflammation and pain, by flindersine and a derivative thereof, along with the moderate anti-inflammatory activity shown by several other compounds isolated from Geijera parviflora leaf extract, support the traditional use of this plant for pain relief by Australian Aboriginal people