1,535 research outputs found
State Taxation of Interstate Commerce
The United States Supreme Court has been confronted with numerous issues which require a reconciliation of the principle of maintaining free interstate trade and that requiring persons engaged in interstate commerce to bear their share of state taxation. In deciding these issues the Court has used various words to state and explain applicable legal tests. To understand these tests the situations from which they were originated, as well as those in which they were applied, should be examined
EXPLORE: A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyria with Recurrent Attacks
Abstract Acute hepatic porphyria comprises a group of rare, genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can experience acute neurovisceral attacks, debilitating chronic symptoms, and long-term complications. There is a lack of multinational, prospective data characterizing the disease and current treatment practices in severely affected patients. EXPLORE is a prospective, multinational, natural history study characterizing disease activity and clinical management in patients with acute hepatic porphyria who experience recurrent attacks. Eligible patients had a confirmed acute hepatic porphyria diagnosis and had experienced ≥3 attacks in the prior 12 months or were receiving prophylactic treatment. A total of 112 patients were enrolled and followed for at least 6 months. In the 12 months prior to the study, patients reported a median (range) of 6 (0-52) acute attacks, with 52 (46%) patients receiving hemin prophylaxis. Chronic symptoms were reported by 73 (65%) patients, with 52 (46%) patients experiencing these daily. During the study, 98 (88%) patients experienced a total of 483 attacks, 77% of which required treatment at a healthcare facility and/or hemin administration (median [range] annualized attack rate 2.0 [0.0-37.0]). Elevated levels of hepatic δ-aminolevulinic acid synthase 1 messenger ribonucleic acid levels, δ-aminolevulinic acid, and porphobilinogen compared with the upper limit of normal in healthy individuals were observed at baseline and increased further during attacks. Patients had impaired quality of life and increased healthcare utilization. Conclusions: Patients experienced attacks often requiring treatment in a healthcare facility and/or with hemin, as well as chronic symptoms that adversely influence day-to-day functioning. In this patient group, the high disease burden and diminished quality of life highlight the need for novel therapies. This article is protected by copyright. All rights reserved.Peer reviewe
A survey of knowledge, attitudes and practice of emergency contraception among university students in Cameroon
<p>Abstract</p> <p>Background</p> <p>Unsafe abortion is a major public health problem in low-and-middle income countries. Young and unmarried women constitute a high risk group for unsafe abortions. It has been estimated that widespread use of emergency contraception may significantly reduce the number of abortion-related morbidity and mortality. The purpose of this study was to evaluate the knowledge, attitudes and experiences on emergency contraceptive pills by the university students in Cameroon in order to develop and refine a national health programme for reducing unwanted pregnancies and their associated morbidity and mortality.</p> <p>Methods</p> <p>A convenient sample of 700 students of the University of Buea (Cameroon) was selected for the study. Data was collected by a self-administered, anonymous and pre-tested questionnaire.</p> <p>Results</p> <p>The response rate was 94.9% (664/700). General level of awareness of emergency contraceptive pills was 63.0% (418/664). However, knowledge of the general features of emergency contraceptive pills was low and misinformation was high among these students. Knowledge differed according to the source of information: informal source was associated with misinformation, while medical and informational sources were associated with better knowledge. Although the students generally had positive attitudes regarding emergency contraceptive pills, up to 65.0% (465/664) believed that emergency contraceptive pills were unsafe. Those with adequate knowledge generally showed favourable attitudes with regards to emergency contraceptive pills (Mann-Whitney U = 2592.5, p = 0.000). Forty-nine students (7.4%) had used emergency contraceptive pills themselves or had a partner who had used them.</p> <p>Conclusion</p> <p>Awareness of emergency contraception pills by Cameroonian students is low and the method is still underused. Strategies to promote use of emergency contraception should be focused on spreading accurate information through medical and informational sources, which have been found to be reliable and associated with good knowledge on emergency contraceptive pills.</p
Dietary supplement use among health care professionals enrolled in an online curriculum on herbs and dietary supplements
BACKGROUND: Although many health care professionals (HCPs) in the United States have been educated about and recommend dietary supplements, little is known about their personal use of dietary supplements and factors associated with their use. METHODS: We surveyed HCPs at the point of their enrollment in an on-line course about dietary supplements between September, 2004 and May, 2005. We used multivariable logistic regression to analyze demographic and practice factors associated with use of dietary supplements. RESULTS: Of the 1249 health care professionals surveyed, 81 % reported having used a vitamin, mineral, or other non-herbal dietary supplements in the last week. Use varied by profession with highest rates among nurses (88%), physician assistants or nurse practitioners (84 %) and the lowest rates among pharmacists (66%) and trainees (72%). The most frequently used supplements were multivitamins (60%), calcium (40%), vitamin B (31%), vitamin C (30%), and fish oil (24%). Factors associated with higher supplement use were older age, female, high knowledge of dietary supplements, and discussing dietary supplements with patients. In our adjusted model, nurses were more likely than other professionals to use a multivitamin and students were more likely to use calcium. CONCLUSION: Among HCPs enrolled in an on-line course about dietary supplements, women, older clinicians, those with higher knowledge and those who talk with patients about dietary supplements had higher use of dietary supplements. Additional research is necessary to understand the impact of professionals' personal use of dietary supplements on communication with patients about them
EXPLORE: A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyria with Recurrent Attacks
BACKGROUND AND AIMS: Acute hepatic porphyria
comprises a group of rare genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can
experience acute neurovisceral attacks, debilitating chronic
symptoms, and long-term complications. There is a lack of
multinational, prospective data characterizing the disease and
current treatment practices in severely affected patients.
APPROACH AND RESULTS: EXPLORE is a prospective,
multinational, natural history study characterizing disease activity and clinical management in patients with acute hepatic
porphyria who experience recurrent attacks. Eligible patients
had a confirmed acute hepatic porphyria diagnosis and had
experienced ≥3 attacks in the prior 12 months or were receiving prophylactic treatment. A total of 112 patients were enrolled and followed for at least 6 months. In the 12 months
before the study, patients reported a median (range) of 6
(0-52) acute attacks, with 52 (46%) patients receiving hemin
prophylaxis. Chronic symptoms were reported by 73 (65%)
patients, with 52 (46%) patients experiencing these daily.
During the study, 98 (88%) patients experienced a total of
483 attacks, 77% of which required treatment at a health
care facility and/or hemin administration (median [range] annualized attack rate 2.0 [0.0-37.0]). Elevated levels of hepatic
δ-aminolevulinic acid synthase 1 messenger ribonucleic acid levels, δ-aminolevulinic acid, and porphobilinogen compared with
the upper limit of normal in healthy individuals were observed
at baseline and increased further during attacks. Patients had
impaired quality of life and increased health care utilization.
CONCLUSIONS: Patients experienced attacks often requiring treatment in a health care facility and/or with hemin, as
well as chronic symptoms that adversely influenced day-to-day
functioning. In this patient group, the high disease burden
and diminished quality of life highlight the need for novel
therapies. (Hepatology 2020;71:1546-1558)
EXPLORE: A prospective, multinational natural history study of patients with acute hepatic porphyria with recurrent attacks
BACKGROUND AND AIMS: Acute hepatic porphyria
comprises a group of rare genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can
experience acute neurovisceral attacks, debilitating chronic
symptoms, and long-term complications. There is a lack of
multinational, prospective data characterizing the disease and
current treatment practices in severely affected patients.
APPROACH AND RESULTS: EXPLORE is a prospective,
multinational, natural history study characterizing disease activity and clinical management in patients with acute hepatic
porphyria who experience recurrent attacks. Eligible patients
had a confirmed acute hepatic porphyria diagnosis and had
experienced ≥3 attacks in the prior 12 months or were receiving prophylactic treatment. A total of 112 patients were enrolled and followed for at least 6 months. In the 12 months
before the study, patients reported a median (range) of 6
(0-52) acute attacks, with 52 (46%) patients receiving hemin
prophylaxis. Chronic symptoms were reported by 73 (65%)
patients, with 52 (46%) patients experiencing these daily.
During the study, 98 (88%) patients experienced a total of
483 attacks, 77% of which required treatment at a health
care facility and/or hemin administration (median [range] annualized attack rate 2.0 [0.0-37.0]). Elevated levels of hepatic
δ-aminolevulinic acid synthase 1 messenger ribonucleic acid levels, δ-aminolevulinic acid, and porphobilinogen compared with
the upper limit of normal in healthy individuals were observed
at baseline and increased further during attacks. Patients had
impaired quality of life and increased health care utilization.
CONCLUSIONS: Patients experienced attacks often requiring treatment in a health care facility and/or with hemin, as
well as chronic symptoms that adversely influenced day-to-day
functioning. In this patient group, the high disease burden
and diminished quality of life highlight the need for novel
therapies. (Hepatology 2020;71:1546-1558)
Revealing the progenitor of SN 2021zby through analysis of the shock-cooling light curve
We present early observations and analysis of the double-peaked Type IIb
supernova (SN IIb) 2021zby. captured the prominent early shock cooling
peak of SN 2021zby within the first 10 days after explosion with a
30-minute cadence. We present optical and near-infrared spectral series of SN
2021zby, including three spectra during the shock cooling phase. Using a
multi-band model fit, we find that the inferred properties of its progenitor
are consistent with a red supergiant or yellow supergiant, with an envelope
mass of 0.3-3.0 M and an envelope radius of 50-350. These inferred progenitor properties are similar to those of other
SNe IIb with double-peak feature, such as SNe 1993J, 2011dh, 2016gkg and
2017jgh. This study further validates the importance of the high cadence and
early coverage in resolving the shape of the shock cooling light curve, while
the multi-band observations, especially UV, is also necessary to fully
constrain the progenitor properties.Comment: 12 pages, 5 figures, 2 tables, submitted to ApJ
A fibril-specific, conformation-dependent antibody recognizes a subset of Aβ plaques in Alzheimer disease, Down syndrome and Tg2576 transgenic mouse brain
Beta-amyloid (Aβ) is thought to be a key contributor to the pathogenesis of Alzheimer disease (AD) in the general population and in adults with Down syndrome (DS). Different assembly states of Aβ have been identified that may be neurotoxic. Aβ oligomers can assemble into soluble prefibrillar oligomers, soluble fibrillar oligomers and insoluble fibrils. Using a novel antibody, OC, recognizing fibrils and soluble fibrillar oligomers, we characterized fibrillar Aβ deposits in AD and DS cases. We further compared human specimens to those obtained from the Tg2576 mouse model of AD. Our results show that accumulation of fibrillar immunoreactivity is significantly increased in AD relative to nondemented aged subjects and those with select cognitive impairments (p < 0.0001). Further, there was a significant correlation between the extent of frontal cortex fibrillar deposit accumulation and dementia severity (MMSE r = −0.72). In DS, we observe an early age of onset and age-dependent accumulation of fibrillar OC immunoreactivity with little pathology in similarly aged non-DS individuals. Tg2576 mice show fibrillar accumulation that can be detected as young as 6 months. Interestingly, fibril-specific immunoreactivity was observed in diffuse, thioflavine S-negative Aβ deposits in addition to more mature neuritic plaques. These results suggest that fibrillar deposits are associated with disease in both AD and in adults with DS and their distribution within early Aβ pathology associated with diffuse plaques and correlation with MMSE suggest that these deposits may not be as benign as previously thought
ANCA-associated vasculitis.
The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of disorders involving severe, systemic, small-vessel vasculitis and are characterized by the development of autoantibodies to the neutrophil proteins leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA). The three AAV subgroups, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic GPA (EGPA), are defined according to clinical features. However, genetic and other clinical findings suggest that these clinical syndromes may be better classified as PR3-positive AAV (PR3-AAV), MPO-positive AAV (MPO-AAV) and, for EGPA, by the presence or absence of ANCA (ANCA+ or ANCA-, respectively). Although any tissue can be involved in AAV, the upper and lower respiratory tract and kidneys are most commonly and severely affected. AAVs have a complex and unique pathogenesis, with evidence for a loss of tolerance to neutrophil proteins, which leads to ANCA-mediated neutrophil activation, recruitment and injury, with effector T cells also involved. Without therapy, prognosis is poor but treatments, typically immunosuppressants, have improved survival, albeit with considerable morbidity from glucocorticoids and other immunosuppressive medications. Current challenges include improving the measures of disease activity and risk of relapse, uncertainty about optimal therapy duration and a need for targeted therapies with fewer adverse effects. Meeting these challenges requires a more detailed knowledge of the fundamental biology of AAV as well as cooperative international research and clinical trials with meaningful input from patients
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