110 research outputs found

    Environmental Sustainability Practices of Albanian Micro Enterprises and SMEs

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    There is a growing global awareness on the importance of sustainability practices. Some major reasons for the growing awareness of sustainability practices are increased legal requirements by governments, customer demands, and political/societal pressure. This paper discuses environmental sustainability practices of micro enterprises and SMEs in Albania. Nine Albanian SMEs were interviewed about their sustainability practices and the results are discussed. The results of this study show that even though there is a lack of detailed sustainability requirements in Albania many SMEs are aware of environmental sustainability and are beginning to implement sustainability practices. For some Albanian SMEs and micro businesses, the implementation of sustainability practices are viewed as a requirement to access lucrative international markets such as the European Union

    Enantiomer‐selective pharmacokinetics and metabolism of ketorolac in children

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110020/1/cptclpt1999381.pd

    Pharmacokinetics and pharmacodynamics of famotidine and ranitidine in critically ill children

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    To characterize and compare acid suppression (pharmacodynamics) and pharmacokinetics of IV famotidine and ranitidine in critically ill children at risk for stress gastritis. Single‐blind, randomized study in PICU patients 6 months to 18 years requiring mechanical ventilation with continuous gastric pH monitoring, randomized to IV famotidine 12 mg/m 2 or ranitidine 60 mg/m 2 when gastric pH 1 hour with serial blood sampling following first dose. Twenty‐four children randomized to either famotidine (n = 12) or ranitidine (n = 12). Sixteen out of twenty‐four completed both PK and PD study arms (7/12 famotidine; 4.7 ± 3.4 years; 9/12 ranitidine; 6.6 ± 4.7 years; p  = 0.38). Time to gastric pH 4.0 and total time pH above 4.0 similar with no difference in pH at 6 and 12 hours ( p  > 0.2). No difference between drugs in clearance, volume of distribution and half‐life ( p  > 0.05). Ratio of AUC pH to AUC drug concentration 0–12 hours after first dose was significantly greater for famotidine (0.06849 ± 0.01460 SD) than ranitidine (0.02453 ± 0.01448; p  < 0.001) demonstrating greater potency of famotidine. pH lowering efficacy of both drugs is similar. Greater potency of famotidine may offer clinical advantage due to lower drug exposure and less frequent dosing to achieve same pH lowering effect.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102678/1/jcph219.pd

    A study of adverse reaction algorithms in a drug surveillance program

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110093/1/cptclpt1985156.pd

    Surveillance of Infectious Diseases Among American Indians and Alaska Natives

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    We assessed participation in public health surveillance networks among Indian Health Service, tribal, and urban (I/T/U) Indian health facilities for a group of infectious diseases, and barriers to participation. We conducted surveys of I/T/U facilities and key informant interviews with representatives of tribal, urban, and national American Indian/Alaska Native (AI/AN) agencies. For the surveys, frequencies and percentages of responses in each response category were calculated. Qualitative methods were used to analyze interview content. The proportion of facilities participating in case reporting is suboptimal across facility types and diseases. Even when reporting is occurring, there is little feedback to tribal agencies. Lack of trust between tribal authorities and state/local governments, lack of feedback on surveillance efforts, and gaps in coordination of activities were identified as barriers to participation in surveillance. Our findings indicate weaknesses in surveillance systems for monitoring infectious diseases among AI/AN people, and have implications for addressing health disparities

    Selinexor, a novel selective inhibitor of nuclear export, reduces SARS-CoV-2 infection and protects the respiratory system in vivo

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    The novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the recent global pandemic. The nuclear export protein (XPO1) has a direct role in the export of SARS-CoV proteins including ORF3b, ORF9b, and nucleocapsid. Inhibition of XPO1 induces anti-inflammatory, anti-viral, and antioxidant pathways. Selinexor is an FDA-approved XPO1 inhibitor. Through bioinformatics analysis, we predicted nuclear export sequences in the ACE-2 protein and confirmed by in vitro testing that inhibition of XPO1 with selinexor induces nuclear localization of ACE-2. Administration of selinexor inhibited viral infection prophylactically as well as therapeutically in vitro. In a ferret model of COVID-19, selinexor treatment reduced viral load in the lungs and protected against tissue damage in the nasal turbinates and lungs in vivo. Our studies demonstrated that selinexor downregulated the pro-inflammatory cytokines IL-1β, IL-6, IL-10, IFN-γ, TNF-α, and GMCSF, commonly associated with the cytokine storm observed in COVID-19 patients. Our findings indicate that nuclear export is critical for SARS-CoV-2 infection and for COVID-19 pathology and suggest that inhibition of XPO1 by selinexor could be a viable anti-viral treatment option

    The contribution of statistical physics to evolutionary biology

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    Evolutionary biology shares many concepts with statistical physics: both deal with populations, whether of molecules or organisms, and both seek to simplify evolution in very many dimensions. Often, methodologies have undergone parallel and independent development, as with stochastic methods in population genetics. We discuss aspects of population genetics that have embraced methods from physics: amongst others, non-equilibrium statistical mechanics, travelling waves, and Monte-Carlo methods have been used to study polygenic evolution, rates of adaptation, and range expansions. These applications indicate that evolutionary biology can further benefit from interactions with other areas of statistical physics, for example, by following the distribution of paths taken by a population through time.Comment: 18 pages, 3 figures, glossary. Accepted in Trend in Ecology and Evolution (to appear in print in August 2011

    Association of IL-4RA single nucleotide polymorphisms, HLA-DR and HLA-DQ in children with Alternaria-sensitive moderate-severe asthma

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    <p>Abstract</p> <p>Background</p> <p>Asthma afflicts 6% to 8% of the United States population, and severe asthma represents approximately 10% of asthmatic patients. Several epidemiologic studies in the United States and Europe have linked <it>Alternaria </it>sensitivity to both persistence and severity of asthma. In order to begin to understand genetic risk factors underlying <it>Alternaria </it>sensitivity and asthma, in these studies we examined T cell responses to <it>Alternaria </it>antigens, HLA Class II restriction and HLA-DQ protection in children with severe asthma.</p> <p>Methods</p> <p>Sixty children with <it>Alternaria</it>-sensitive moderate-severe asthma were compared to 49 children with <it>Alternaria</it>-sensitive mild asthma. We examined HLA-DR and HLA-DQ frequencies in <it>Alternaria</it>-sensitive asthmatic by HLA typing. To determine ratios of Th1/Th2 <it>Alternaria</it>-specific T-cells, cultures were stimulated in media alone, <it>Alternaria alternata </it>extract and Alt a1. Sensitivity to IL-4 stimulation was measured by up-regulation of CD23 on B cells.</p> <p>Results</p> <p>Children with <it>Alternaria</it>-sensitive moderate-severe asthma trended to have increased sensitivities to <it>Cladosporium </it>(46% versus 35%), to <it>Aspergillus </it>(43% versus 28%), and significantly increased sensitivities to trees (78% versus 57%) and to weeds (68% versus 48%). The IL-4RA ile75val polymorphism was significantly increased in <it>Alternaria</it>-sensitive moderate-severe asthmatics, 83% (0.627 allele frequency) compared to <it>Alternaria</it>-sensitive mild asthmatics, 57% (0.388 allele frequency). This was associated with increased sensitivity to IL-4 stimulation measured by significantly increased IL-4 stimulated CD23 expression on CD19+ and CD86+CD19+ B cells of <it>Alternaria</it>-sensitive moderate-severe asthmatics. IL-5 and IL-13 synthesis was significantly increased in <it>Alternaria</it>-sensitive moderate-severe asthmatics compared to mild asthmatics to <it>Alternaria </it>extract and Alt a1 stimulation. The frequency of HLA-DQB1*03 allele was significantly decreased in <it>Alternaria</it>-sensitive moderate-severe asthmatics compared to mild asthmatics, 39% versus 63%, with significantly decreased allele frequency, 0.220 versus 0.398.</p> <p>Summary</p> <p>In children with <it>Alternaria</it>-sensitive moderate severe asthma, there was an increased Th2 response to <it>Alternaria </it>stimulation and increased sensitivity to IL-4 stimulation. This skewing towards a Th2 response was associated with an increased frequency of the IL-4RA ile75val polymorphism. In evaluating the HLA association, there was a decreased frequency of HLA-DQB1*03 in <it>Alternaria</it>-sensitive moderate severe asthmatic children consistent with previous studies suggest that HLA-DQB1*03 may be protective against the development of mold-sensitive severe asthma.</p

    Resectable pancreatic small cell carcinoma

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    Primary pancreatic small cell carcinoma (SCC) is rare, with just over 30 cases reported in the literature. Only 7 of these patients underwent surgical resection with a median survival of 6 months. Prognosis of SCC is therefore considered to be poor, and the role of adjuvant therapy is uncertain. Here we report two institutions' experience with resectable pancreatic SCC. Six patients with pancreatic SCC treated at the Johns Hopkins Hospital (4 patients) and the Mayo Clinic (2 patients) were identified from prospectively collected pancreatic cancer databases and re-reviewed by pathology. All six patients underwent a pancreaticoduodenectomy. Clinicopathologic data were analyzed, and the literature on pancreatic SCC was reviewed. Median age at diagnosis was 50 years (range 27–60). All six tumors arose in the head of the pancreas. Median tumor size was 3 cm, and all cases had positive lymph nodes except for one patient who only had five nodes sampled. There were no perioperative deaths and three patients had at least one postoperative complication. All six patients received adjuvant therapy, five of whom were given combined modality treatment with radiation, cisplatin, and etoposide. Median survival was 20 months with a range of 9–173 months. The patient who lived for 9 months received chemotherapy only, while the patient who lived for 173 months was given chemoradiation with cisplatin and etoposide and represents the longest reported survival time from pancreatic SCC to date. Pancreatic SCC is an extremely rare form of cancer with a poor prognosis. Patients in this surgical series showed favorable survival rates when compared to prior reports of both resected and unresectable SCC. Cisplatin and etoposide appears to be the preferred chemotherapy regimen, although its efficacy remains uncertain, as does the role of combined modality treatment with radiation
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