Improving the efficiency of a hospital emergency department: a simulation study with indirectly imputed service-time distributions

This paper presents a case study which uses simulation to analyze patient flows in a hospital emergency department in Hong Kong. We first analyze the impact of the enhancements made to the system after the relocation of the Emergency Department. After that, we developed a simulation model (using ARENA) to capture all the key relevant processes of the department. When developing the simulation model, we faced the challenge that the data kept by the Emergency Department were incomplete so that the service-time distributions were not directly obtainable. We propose a simulation–optimization approach (integrating simulation with meta-heuristics) to obtain a good set of estimate of input parameters of our simulation model. Using the simulation model, we evaluated the impact of possible changes to the system by running different scenarios. This provides a tool for the operations manager in the Emergency Department to “foresee” the impact on the daily operations when making possible changes (such as, adjusting staffing levels or shift times), and consequently make much better decisions.     

Lipophilic methylene blue analogues enhance mitochondrial function and increase frataxin levels in a cellular model of Friedreich’s ataxia

Friedreich’s ataxia (FRDA) is an autosomal recessive neurodegenerative disorder resulting from reduced expression of the protein frataxin (FXN). Although its function is not fully understood, frataxin appears to help assemble iron sulfur clusters; these are critical for the function of many proteins, including those needed for mitochondrial energy production. Finding ways to increase FXN levels has been a major therapeutic strategy for this disease. Previously, we described a novel series of methylene violet analogues and their structural optimization as potential therapeutic agents for neurodegenerative and mitochondrial disorders. Presently, a series of methylene blue analogues has been synthesized and characterized for their in vitro biochemical and biological properties in cultured Friedreich’s ataxia lymphocytes. Favorable methylene blue analogues were shown to increase frataxin levels and mitochondrial biogenesis, and to improve aconitase activity. The analogues were found to be good ROS scavengers, and able to protect cultured FRDA lymphocytes from oxidative stress resulting from inhibition of complex I and from glutathione depletion. The analogues also preserved mitochondrial membrane potential and augmented ATP production. Our results suggest that analogue 5, emerging from the initial structure of the parent compound methylene blue (MB), represents a promising lead structure and lacks the cytotoxicity associated with the parent compound MB.     

Y-chromosomal diversity in Haiti and Jamaica: contrasting levels of sex-biased gene flow

Although previous studies have characterized the genetic structure of populations from Haiti and Jamaica using classical and autosomal STR polymorphisms, the patrilineal influences that are present in these countries have yet to be explored. To address this lacuna, the current study aims to investigate, for the first time, the potential impact of different ancestral sources, unique colonial histories, and distinct family structures on the paternal profile of both groups. According to previous reports examining populations from the Americas, island-specific demographic histories can greatly impact population structure, including various patterns of sex-biased gene flow. Also, given the contrasting autosomal profiles provided in our earlier study (Simms et al.: Am J Phys Anthropol 142 (2010) 49-66), we hypothesize that the degree and directionality of gene flow from Europeans, Africans, Amerindians, and East Asians are dissimilar in the two countries. To test this premise, 177 high-resolution Y-chromosome binary markers and 17 Y-STR loci were typed in Haiti (n = 123) and Jamaica (n = 159) and subsequently utilized for phylogenetic comparisons to available reference collections encompassing Africa, Europe, Asia (East and South), and the New World. Our results reveal that both studied populations exhibit a predominantly South-Saharan paternal component, with haplogroups A1b-V152, A3-M32, B2-M182, E1a-M33, E1b1a-M2, E2b-M98, and R1b2-V88 comprising 77.2% and 66.7% of the Haitian and Jamaican paternal gene pools, respectively. Yet, European derived chromosomes (i.e., haplogroups G2a*-P15, I-M258, R1b1b-M269, and T-M184) were detected at commensurate levels in Haiti (20.3%) and Jamaica (18.9%), whereas Y-haplogroups indicative of Chinese [O-M175 (3.8%)] and Indian [H-M69 (0.6%) and L-M20 (0.6%)] ancestry were restricted to Jamaica.     

First Report of Rhizoctonia solani AG‐7 on Cotton in Egypt

Eighty‐two isolates of Rhizoctonia solani were recorded from roots of naturally‐infected seedlings of the Egyptian cotton (Gossypium barbadense L.). Anastomosis groups (AGs) of the isolates were determined by using 13 different AGs testers. Three (3.7%) of the isolates were identified as R. solani AG7, while the remaining isolates were belonging to the AG 2‐1, AG4 and AG5. The identification of the three isolates was based on the frequency of the C2 reaction with the AG7 tester isolate. No fusion was observed between AG7 and isolates representing the other 13 AGs. Colonies of AG7 isolates grown on potato dextrose agar (PDA), malt yeast agar (MYA) and melt peptone agar (MPA) were brown to dark brown with aerial mycelium and sclerotia. The isolates had pitted sclerotial clusters and brownish exudates after 21 days of culturing on PDA, but without clear zonation. Pathogenicity test under greenhouse conditions revealed that AG7 caused the common symptoms of damping–off, which included seed rot, lesions on the hypocotyls and root rot.     

Association of spermatogenic failure with the b2/b3 partial AZFc deletion

Infertility affects around 1 in 10 men and in most cases the cause is unknown. The Y chromosome plays an important role in spermatogenesis and specific deletions of this chromosome, the AZF deletions, are associated with spermatogenic failure. Recently partial AZF deletions have been described but their association with spermatogenic failure is unclear. Here we screened a total of 339 men with idiopathic spermatogenic failure, and 256 normozoospermic ancestry-matched men for chromosome microdeletions including AZFa, AZFb, AZFc, and the AZFc partial deletions (gr/gr, b1/b3 and b2/b3).AZFa and AZFc deletions were identified in men with severe spermatogenic failure at similar frequencies to those reported elsewhere. Gr/gr deletions were identified in case and control populations at 5.83% and 6.25% respectively suggesting that these deletions are not associated with spermatogenic failure. However, b2/b3 deletions were detected only in men with spermatogenic failure and not in the normospermic individuals. Combined with our previous data this shows an association of the b2/b3 deletion (p = 0.0318) with spermatogenic failure in some populations. We recommend screening for this deletion in men with unexplained spermatogenic failure.     

Autopsy Prevalence of Tuberculosis and Other Potentially Treatable Infections among Adults with Advanced HIV Enrolled in Out-Patient Care in South Africa

BackgroundEarly mortality among HIV-positive adults starting antiretroviral therapy (ART) remains high in resource-limited settings, with tuberculosis (TB) the leading cause of death. However, current methods to estimate TB-related deaths are inadequate and most autopsy studies do not adequately represent those attending primary health clinics (PHCs). This study aimed to determine the autopsy prevalence of TB and other infections in adults enrolled at South African PHCs in the context of a pragmatic trial of empiric TB treatment (“TB Fast Track”).ConclusionsTB, followed by bacterial infections, were the leading findings at autopsy among adults with advanced HIV enrolled from primary care clinics. To reduce mortality, strategies are needed to identify and direct those at highest risk into a structured pathway that includes expedited investigation and/or treatment of TB and other infections.     

Molecular insights into the klotho-dependent, endocrine mode of action of fibroblast growth factor 19 subfamily members

Unique among fibroblast growth factors (FGFs), FGF19, -21, and -23 act in an endocrine fashion to regulate energy, bile acid, glucose, lipid, phosphate, and vitamin D homeostasis. These FGFs require the presence of Klotho/betaKlotho in their target tissues. Here, we present the crystal structures of FGF19 alone and FGF23 in complex with sucrose octasulfate, a disaccharide chemically related to heparin. The conformation of the heparin-binding region between beta strands 10 and 12 in FGF19 and FGF23 diverges completely from the common conformation adopted by paracrine-acting FGFs. A cleft between this region and the beta1-beta2 loop, the other heparin-binding region, precludes direct interaction between heparin/heparan sulfate and backbone atoms of FGF19/23. This reduces the heparin-binding affinity of these ligands and confers endocrine function. Klotho/betaKlotho have evolved as a compensatory mechanism for the poor ability of heparin/heparan sulfate to promote binding of FGF19, -21, and -23 to their cognate receptors.     

Synthesis and cardiovascular activity of metoprolol analogues

The synthesis of four novel analogues of metoprolol, a well-known beta1-blocker used to reduce arterial blood pressure, is described. The preparation of (2S,2'S)-7, (2R,2'S)-7, (2R,2'R)-8, and (2S,2'R)-8 was based on the reaction of racemic 2-[4-(2'-methoxyethyl)-phenoxymethyl]-oxirane (4) with (R)- or (S)-2-amino-1-butanol. Salient characteristics of analogues 7 and 8 relative to metoprolol are the incorporation of an additional stereogenic center, as well as a methyl group and a hydroxyl function on the nitrogen-containing chain. These novel derivatives present significant hypotensive and bradycardiac activity, although no blocking action toward beta1 and beta2 adrenergic receptor.