Symmetric inclusion-exclusion

One form of the inclusion-exclusion principle asserts that if A and B are functions of finite sets then A(S) is the sum of B(T) over all subsets T of S if and only if B(S) is the sum of (-1)^|S-T| A(T) over all subsets T of S. If we replace B(S) with (-1)^|S| B(S), we get a symmetric form of inclusion-exclusion: A(S) is the sum of (-1)^|T| B(T) over all subsets T of S if and only if B(S) is the sum of (-1)^|T| A(T) over all subsets T of S. We study instances of symmetric inclusion-exclusion in which the functions A and B have combinatorial or probabilistic interpretations. In particular, we study cases related to the Polya-Eggenberger urn model in which A(S) and B(S) depend only on the cardinality of S.Comment: 10 page

Metabolic, hygric and ventilatory physiology of a hypermetabolic marsupial, the honey possum (Tarsipes rostratus)

The honey possum is the only non-volant mammal to feed exclusively on a diet of nectar and pollen. Like other mammalian and avian nectarivores, previous studies indicated that the honey possum's basal metabolic rate was higher than predicted for a marsupial of equivalent body mass. However, these early measurements have been questioned. We re-examined the basal metabolic rate (2.52 +/- A 0.222 ml O(2) g(-1) h(-1)) of the honey possum and confirm that it is indeed higher (162%) than predicted for other marsupials both before and after accounting for phylogenetic history. This, together with its small body mass (5.4 +/- A 0.14 g; 1.3% of that predicted by phylogeny) may be attributed to its nectarivorous diet and mesic distribution. Its high-basal metabolic rate is associated with a high-standard body temperature (36.6 +/- A 0.48A degrees C) and oxygen extraction (19.4%), but interestingly the honey possum has a high point of relative water economy (17.0A degrees C) and its standard evaporative water loss (4.33 +/- A 0.394 mg H(2)O g(-1) h(-1)) is not elevated above that of other marsupials, despite its mesic habitat and high dietary water intake.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Lower cerebrospinal fluid/plasma fibroblast growth factor 21 (FGF21) ratios and placental FGF21 production in gestational diabetes

Objectives: Circulating Fibroblast Growth Factor 21 (FGF21) levels are increased in insulin resistant states such as obesity, type 2 diabetes mellitus and gestational diabetes mellitus (GDM). In addition, GDM is associated with serious maternal and fetal complications. We sought to study human cerebrospinal fluid (CSF) and corresponding circulating FGF21 levels in women with gestational diabetes mellitus (GDM) and in age and BMI matched control subjects. We also assessed FGF21 secretion from GDM and control human placental explants. Design: CSF and corresponding plasma FGF21 levels of 24 women were measured by ELISA [12 GDM (age: 26–47 years, BMI: 24.3–36.3 kg/m2) and 12 controls (age: 22–40 years, BMI: 30.1–37.0 kg/m2)]. FGF21 levels in conditioned media were secretion from GDM and control human placental explants were also measured by ELISA. Results: Glucose, HOMA-IR and circulating NEFA levels were significantly higher in women with GDM compared to control subjects. Plasma FGF21 levels were significantly higher in women with GDM compared to control subjects [234.3 (150.2–352.7) vs. 115.5 (60.5–188.7) pg/ml; P<0.05]. However, there was no significant difference in CSF FGF21 levels in women with GDM compared to control subjects. Interestingly, CSF/Plasma FGF21 ratio was significantly lower in women with GDM compared to control subjects [0.4 (0.3–0.6) vs. 0.8 (0.5–1.6); P<0.05]. FGF21 secretion into conditioned media was significantly lower in human placental explants from women with GDM compared to control subjects (P<0.05). Conclusions: The central actions of FGF21 in GDM subjects maybe pivotal in the pathogenesis of insulin resistance in GDM subjects. The significance of FGF21 produced by the placenta remains uncharted and maybe crucial in our understanding of the patho-physiology of GDM and its associated maternal and fetal complications. Future research should seek to elucidate these points

The Architectural Design Rules of Solar Systems based on the New Perspective

On the basis of the Lunar Laser Ranging Data released by NASA on the Silver Jubilee Celebration of Man Landing on Moon on 21st July 1969-1994, theoretical formulation of Earth-Moon tidal interaction was carried out and Planetary Satellite Dynamics was established. It was found that this mathematical analysis could as well be applied to Star and Planets system and since every star could potentially contain an extra-solar system, hence we have a large ensemble of exoplanets to test our new perspective on the birth and evolution of solar systems. Till date 403 exoplanets have been discovered in 390 extra-solar systems. I have taken 12 single planet systems, 4 Brown Dwarf - Star systems and 2 Brown Dwarf pairs. Following architectural design rules are corroborated through this study of exoplanets. All planets are born at inner Clarke Orbit what we refer to as inner geo-synchronous orbit in case of Earth-Moon System. By any perturbative force such as cosmic particles or radiation pressure, the planet gets tipped long of aG1 or short of aG1. Here aG1 is inner Clarke Orbit. The exoplanet can either be launched on death spiral as CLOSE HOT JUPITERS or can be launched on an expanding spiral path as the planets in our Solar System are. It was also found that if the exo-planet are significant fraction of the host star then those exo-planets rapidly migrate from aG1 to aG2 and have very short Time Constant of Evolution as Brown Dwarfs have. This vindicates our basic premise that planets are always born at inner Clarke Orbit. This study vindicates the design rules which had been postulated at 35th COSPAR Scientific Assembly in 2004 at Paris, France, under the title ,New Perspective on the Birth & Evolution of Solar Systems.Comment: This paper has been reported to Earth,Moon and Planets Journal as MOON-S-09-0007

Comparative physiology of Australian quolls (Dasyurus; Marsupialia)

Quolls (Dasyurus) are medium-sized carnivorous dasyurid marsupials. Tiger (3,840 g) and eastern quolls (780 g) are mesic zone species, northern quolls (516 g) are tropical zone, and chuditch (1,385 g) were once widespread through the Australian arid zone. We found that standard physiological variables of these quolls are consistent with allometric expectations for marsupials. Nevertheless, inter-specific patterns amongst the quolls are consistent with their different environments. The lower T ^sub b^ of northern quolls (34°C) may provide scope for adaptive hyperthermia in the tropics, and they use torpor for energy/water conservation, whereas the larger mesic species (eastern and tiger quolls) do not appear to. Thermolability varied from little in eastern (0.035°C °C^sup -1^) and tiger quolls (0.051°C ºC^sup -1^) to substantial in northern quolls (0.100°C ºC^sup -1^) and chuditch (0.146°C ºC^sup -1^), reflecting body mass and environment. Basal metabolic rate was higher for eastern quolls (0.662 ± 0.033 ml O^sub 2^ g^sup -1^ h^sup -1^), presumably reflecting their naturally cool environment. Respiratory ventilation closely matched metabolic demand, except at high ambient temperatures where quolls hyperventilated to facilitate evaporative heat loss; tiger and eastern quolls also salivated. A higher evaporative water loss for eastern quolls (1.43 ± 0.212 mg H^sub 2^O g^sup -1^ h^sup -1^) presumably reflects their more mesic distribution. The point of relative water economy was low for tiger (-1.3°C), eastern (-12.5°C) and northern (+3.3) quolls, and highest for the chuditch (+22.6°C). We suggest that these differences in water economy reflect lower expired air temperatures and hence lower respiratory evaporative water loss for the arid-zone chuditch relative to tropical and mesic quolls

The per-protocol effect of immediate versus deferred antiretroviral therapy initiation

OBJECTIVE: The START trial found a lower risk of a composite clinical outcome in HIV-positive individuals assigned to immediate initiation of antiretroviral therapy (ART) compared with those assigned to deferred initiation. However, 30% of those assigned to deferred initiation started ART earlier than the protocol specified. To supplement the published intention-to-treat effect estimates, here we estimate the per-protocol effect of immediate versus deferred ART initiation in START. DESIGN: The START trial randomized 4685 HIV-positive participants with CD4 counts > 500 /mm to start ART immediately after randomization (immediate initiation group) or to wait until the CD4 count dropped below 350 cells/mm or an AIDS diagnosis (deferred initiation group). METHODS: We used the parametric g-formula to estimate and compare the cumulative 5-year risk of the composite clinical outcome in the immediate and deferred initiation groups had all the trial participants adhered to the protocol. RESULTS: We estimated that the 5-year risk of the composite outcome would have been 3.2% under immediate ART initiation and 7.0% under deferred initiation. The difference of 3.8% (95% confidence interval 1.5,6.5) was larger than the intention-to-treat effect estimate of 3.1%, corresponding to a difference in effect estimates of 0.72% (-0.35,2.35). CONCLUSIONS: The intention-to-treat effect estimate may underestimate the benefit of immediate ART initiation by 23%. This estimate can be used by patients and policy makers who need to understand the full extent of the benefit of changes in ART initiation policies

A Topical Microbicide Gel Formulation of CCR5 Antagonist Maraviroc Prevents HIV-1 Vaginal Transmission in Humanized RAG-hu Mice

For prevention of HIV infection many currently licensed anti-HIV drugs and new ones in the pipeline show potential as topically applied microbicides. While macaque models have been the gold standard for in vivo microbicide testing, they are expensive and sufficient numbers are not available. Therefore, a small animal model that facilitates rapid evaluation of potential candidates for their preliminary efficacy is urgently needed in the microbicide field. We previously demonstrated that RAG-hu humanized mouse model permits HIV-1 mucosal transmission via both vaginal and rectal routes and that oral pre-exposure chemo-prophylactic strategies could be tested in this system. Here in these proof-of-concept studies, we extended this system for topical microbicide testing using HIV-1 as the challenge virus. Maraviroc, a clinically approved CCR5 inhibitor drug for HIV treatment, was formulated as a microbicide gel at 5 mM concentration in 2.2% hydroxyl ethyl cellulose. Female RAG-hu mice were challenged vaginally with HIV-1 an hour after intravaginal application of the maraviroc gel. Our results showed that maraviroc gel treated mice were fully protected against vaginal HIV-1 challenge in contrast to placebo gel treated mice which all became infected. These findings highlight the utility of the humanized mouse models for microbicide testing and, together with the recent data from macaque studies, suggest that maraviroc is a promising candidate for future microbicide clinical trials in the field

Primary care follow up of patients discharged from the emergency department: a retrospective study

BACKGROUND: The visit to the emergency department (ED) constitutes a brief, yet an important point in the continuum of medical care. The aim of our study was to evaluate the continuity of care of adult ED visitors. METHODS: We retrospectively reviewed all ED discharge summaries for over a month 's period. The ED chart, referral letter and the patient's primary care file were reviewed. Data collected included: age, gender, date and hour of ED visit, documentation of ED referral and ED discharge letter in the primary care file. RESULTS: 359 visits were eligible for the study. 192 (53.5%) of the patients were women, average age 54.1 ± 18.7 years (mean ± SD). 214 (59.6%) of the visits were during working hours of primary care clinics ("working hours"), while the rest were "out of hours" visits. Only 196 (54.6%) of patients had a referral letter, usually from their family physician. A third (71/214) of "working hours" visits were self referrals, the rate rose to 63.5% (92/145) of "out of hours" visits (p < 0.0001). The ED discharge letter was found in 50% (179/359) of the primary care files. A follow-up visit was documented in only 31% (111/359). Neither follow up visit nor discharge letter were found in 43% of the files (153/359). CONCLUSIONS: We have found a high rate of ED self referrals throughout the day together with low documentation rates of ED visits in the primary care charts. Our findings point to a poor continuity of care of ED attendees

A statistical framework to evaluate virtual screening

<p>Abstract</p> <p>Background</p> <p>Receiver operating characteristic (ROC) curve is widely used to evaluate virtual screening (VS) studies. However, the method fails to address the "early recognition" problem specific to VS. Although many other metrics, such as RIE, BEDROC, and pROC that emphasize "early recognition" have been proposed, there are no rigorous statistical guidelines for determining the thresholds and performing significance tests. Also no comparisons have been made between these metrics under a statistical framework to better understand their performances.</p> <p>Results</p> <p>We have proposed a statistical framework to evaluate VS studies by which the threshold to determine whether a ranking method is better than random ranking can be derived by bootstrap simulations and 2 ranking methods can be compared by permutation test. We found that different metrics emphasize "early recognition" differently. BEDROC and RIE are 2 statistically equivalent metrics. Our newly proposed metric SLR is superior to pROC. Through extensive simulations, we observed a "seesaw effect" – overemphasizing early recognition reduces the statistical power of a metric to detect true early recognitions.</p> <p>Conclusion</p> <p>The statistical framework developed and tested by us is applicable to any other metric as well, even if their exact distribution is unknown. Under this framework, a threshold can be easily selected according to a pre-specified type I error rate and statistical comparisons between 2 ranking methods becomes possible. The theoretical null distribution of SLR metric is available so that the threshold of SLR can be exactly determined without resorting to bootstrap simulations, which makes it easy to use in practical virtual screening studies.</p