bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dosimetry in differentiated thyroid carcinoma
Authors: Mínguez Pablo , Genolla José , Celeiro José Javier , Fombellida José Cruz 
Published: December 2012

Purpose:The aim of this study has been to perform a dosimetric study in the treatments of differentiated thyroid cancer (DTC) performed in our center in order to find a dose–effect correlation.Methods:Thirty patients treated for DTC with 3700 MBq of131I have been included in this study. For reasons of radiological protection all of them spent two nights as inpatients. Dose rate at 1 m from all patients was measured approximately 20 and 44 h after the administration of the radioiodine and a whole body scan in the gamma camera was performed approximately 1 week later. With those measurements and by using a model of two compartments the activities in thyroid bed remnants and in the whole body were calculated as a function of time. The integration of both activities yields the corresponding cumulated activities. Absorbed doses to thyroid bed remnants and to the whole body can be calculated following the MIRDOSE method—that is, by multiplying the corresponding cumulated activities by the corresponding S factors.Results:The absorbed doses to thyroid bed remnants calculated in this study fall into a very wide range (13–1161 Gy) and showed the highest correlation factors with the following parameters: the absorbed dose rate to thyroid bed remnants, the cumulated activity in thyroid bed remnants, and the maximum radioiodine uptake in thyroid bed remnants. The absorbed doses to the whole body range from 0.12 to 0.23 Gy. The ablation was successful in all patients, and in spite of the wide range of absorbed doses to thyroid bed remnants obtained, no dose–effect correlation could be obtained.Conclusions:Facing DTC treatments from a dosimetric viewpoint in which a predosimetry to calculate the activity of131I to be administered is performed is a subject difficult to handle. This statement is based on the fact that although a very wide range of absorbed doses to thyroid bed remnants was obtained (including several absorbed doses well below some dose thresholds previously published to achieve ablation of thyroid bed remnants), ablation of thyroid bed remnants was successful for all patients and therefore no dose–effect correlation could be determined.
Comparison of Four Commercially Available Avidity Tests for Toxoplasma gondii-Specific IgG Antibodies
Authors: Villard O. , Breit L. , Cimon B. , Franck J. , Fricker-Hidalgo H. , Godineau N. , Houze S. , Paris L. , Pelloux H. , Villena I. , Candolfi E. 
Published: December 2012

ABSTRACT

Toxoplasma
infection in pregnant women may cause congenital toxoplasmosis. Diagnosis of infection is based on serological tests aimed at detecting IgM and IgG antibodies against
Toxoplasma gondii
. However, IgM antibodies are not an accurate marker for discriminating between acute and latent infection. Detection of residual or persistent IgM may occur months or even years after primary infection, while the IgG avidity test is a rapid means of identifying latent infections in pregnant women who exhibit both IgG and IgM anti-
Toxoplasma
antibodies on initial testing during pregnancy. In this study, we assessed and compared the performances of four commercially available
Toxoplasma
IgG avidity tests in immunocompetent and immunocompromised patients with acute and latent toxoplasmosis. The positive predictive value of high avidity to confirm latent toxoplasmosis was 100% for all the assays, indicating that high avidity is a hallmark of latent infection. However, the negative predictive value of high avidity ranged from 99.2% (bioMérieux) to 95.3% (Abbott), indicating that acute toxoplasmosis could not be reliably diagnosed based on low IgG avidity alone. Thus, the avidity test provides a rapid means for identifying latent
Toxoplasma
infection in immunocompetent pregnant women presenting both IgG and IgM anti-
Toxoplasma
antibodies on initial testing. In terms of cost-effectiveness, avidity testing is a powerful tool that optimizes screening and follow-up of pregnant women while minimizing the costs of screening by avoiding subsequent costly maternal and fetal investigation and unnecessary treatment. The cheapest assay, Vidas Toxo IgG Avidity, also had the best performance for the diagnosis of latent toxoplasmosis.
Poor Immune Responses of Newborn Rhesus Macaques to Measles Virus DNA Vaccines Expressing the Hemagglutinin and Fusion Glycoproteins
Authors: Polack Fernando P. , Lydy Shari L. , Lee Sok-Hyong , Rota Paul A. , Bellini William J. , Adams Robert J. , Robinson Harriet L. , Griffin Diane E. 
Published: December 2012

ABSTRACTA vaccine that would protect young infants against measles could facilitate elimination efforts and decrease morbidity and mortality in developing countries. However, immaturity of the immune system is an important obstacle to the development of such a vaccine. In this study, DNA vaccines expressing the measles virus (MeV) hemagglutinin (H) protein or H and fusion (F) proteins, previously shown to protect juvenile macaques, were used to immunize groups of 4 newborn rhesus macaques. Monkeys were inoculated intradermally with 200 μg of each DNA at birth and at 10 months of age. As controls, 2 newborn macaques were similarly vaccinated with DNA encoding the influenza virus H5, and 4 received one dose of the current live attenuated MeV vaccine (LAV) intramuscularly. All monkeys were monitored for development of MeV-specific neutralizing and binding IgG antibody and cytotoxic T lymphocyte (CTL) responses. These responses were poor compared to the responses induced by LAV. At 18 months of age, all monkeys were challenged intratracheally with a wild-type strain of MeV. Monkeys that received the DNA vaccine encoding H and F, but not H alone, were primed for an MeV-specific CD8+CTL response but not for production of antibody. LAV-vaccinated monkeys were protected from rash and viremia, while DNA-vaccinated monkeys developed rashes, similar to control monkeys, but had 10-fold lower levels of viremia. We conclude that vaccination of infant macaques with DNA encoding MeV H and F provided only partial protection from MeV infection.
Gene Expression Profile and Immunological Evaluation of Unique Hypothetical Unknown Proteins of Mycobacterium leprae by Using Quantitative Real-Time PCR
Authors: Kim Hee Jin , Prithiviraj Kalyani , Groathouse Nathan , Brennan Patrick J. , Spencer John S. 
Published: December 2012

ABSTRACT

The cell-mediated immunity (CMI)-based
in vitro
gamma interferon release assay (IGRA) of
Mycobacterium leprae
-specific antigens has potential as a promising diagnostic means to detect those individuals in the early stages of
M. leprae
infection. Diagnosis of leprosy is a major obstacle toward ultimate disease control and has been compromised in the past by the lack of specific markers. Comparative bioinformatic analysis among mycobacterial genomes identified potential
M. leprae
-specific proteins called “hypothetical unknowns.” Due to massive gene decay and the prevalence of pseudogenes, it is unclear whether any of these proteins are expressed or are immunologically relevant. In this study, we performed cDNA-based quantitative real-time PCR to investigate the expression status of 131 putative open reading frames (ORFs) encoding hypothetical unknowns. Twenty-six of the
M. leprae
-specific antigen candidates showed significant levels of gene expression compared to that of ESAT-6 (ML0049), which is an important T cell antigen of low abundance in
M. leprae
. Fifteen of 26 selected antigen candidates were expressed and purified in
Escherichia coli
. The seroreactivity to these proteins of pooled sera from lepromatous leprosy patients and cavitary tuberculosis patients revealed that 9 of 15 recombinant hypothetical unknowns elicited
M. leprae
-specific immune responses. These nine proteins may be good diagnostic reagents to improve both the sensitivity and specificity of detection of individuals with asymptomatic leprosy.
Adults 65 Years Old and Older Have Reduced Numbers of Functional Memory T Cells to Respiratory Syncytial Virus Fusion Protein
Authors: Cherukuri Anu , Patton Kathryn , Gasser Robert A. , Zuo Fengrong , Woo Jennifer , Esser Mark T. , Tang Roderick S. 
Published: December 2012

ABSTRACTRespiratory syncytial virus (RSV) infects elderly (≥65 years) adults, causing medically attended illness and hospitalizations. While RSV neutralizing antibody levels correlate inversely with RSV-associated hospitalization in the elderly, the role of RSV-specific T cells in preventing disease in the elderly remains unclear. We examined RSV-specific humoral, mucosal, and cellular immune profiles in healthy elderly (65 to 85 years) and young (20 to 30 years) adults. RSV neutralization antibody titers in the elderly (10.5 ± 2.2 log2) and young (10.5 ± 2.1 log2) were similar. In contrast, levels of RSV F protein-specific gamma interferon (IFN-γ)-producing T cells were lower in elderly (180 ± 80 spot-forming cells [SFC]/106peripheral blood mononuclear cells [PBMC]) than in young adults (1,250 ± 420 SFC/106PBMC). Higher levels of interleukin-13 (IL-13; 3,000 ± 1,000 pg/ml) in cultured PBMC supernatants and lower frequency of RSV F-specific CD107a+CD8+T cells (3.0% ± 1.6% versus 5.0% ± 1.6%) were measured in PBMC from elderly than young adults. These results suggest that deficient RSV F-specific T cell responses contribute to susceptibility to severe RSV disease in elderly adults.
Distinct HIV-1 Escape Patterns Selected by Cytotoxic T Cells with Identical Epitope Specificity
Authors: Yagita Yuichi , Kuse Nozomi , Kuroki Kimiko , Gatanaga Hiroyuki , Carlson Jonathan M. , Chikata Takayuki , Brumme Zabrina L. , Murakoshi Hayato , Akahoshi Tomohiro , Pfeifer Nico , Mallal Simon , John Mina , Ose Toyoyuki , Matsubara Haruki , Kanda Ryo , Fukunaga Yuko , Honda Kazutaka , Kawashima Yuka , Ariumi Yasuo , Oka Shinichi , Maenaka Katsumi , Takiguchi Masafumi 
Published: December 2012

ABSTRACT

Pol283-8-specific, HLA-B*51:01-restricted, cytotoxic T cells (CTLs) play a critical role in the long-term control of HIV-1 infection. However, these CTLs select for the reverse transcriptase (RT) I135X escape mutation, which may be accumulating in circulating HIV-1 sequences. We investigated the selection of the I135X mutation by CTLs specific for the same epitope but restricted by HLA-B*52:01. We found that Pol283-8-specific, HLA-B*52:01-restricted CTLs were elicited predominantly in chronically HIV-1-infected individuals. These CTLs had a strong ability to suppress the replication of wild-type HIV-1, though this ability was weaker than that of HLA-B*51:01-restricted CTLs. The crystal structure of the HLA-B*52:01-Pol283-8 peptide complex provided clear evidence that HLA-B*52:01 presents the peptide similarly to HLA-B*51:01, ensuring the cross-presentation of this epitope by both alleles. Population level analyses revealed a strong association of HLA-B*51:01 with the I135T mutant and a relatively weaker association of HLA-B*52:01 with several I135X mutants in both Japanese and predominantly Caucasian cohorts. An
in vitro
viral suppression assay revealed that the HLA-B*52:01-restricted CTLs failed to suppress the replication of the I135X mutant viruses, indicating the selection of these mutants by the CTLs. These results suggest that the different pattern of I135X mutant selection may have resulted from the difference between these two CTLs in the ability to suppress HIV-1 replication.
Outer Domain of HIV-1 gp120: Antigenic Optimization, Structural Malleability, and Crystal Structure with Antibody VRC-PG04
Authors: Joyce M. Gordon , Kanekiyo Masaru , Xu Ling , Biertümpfel Christian , Boyington Jeffrey C. , Moquin Stephanie , Shi Wei , Wu Xueling , Yang Yongping , Yang Zhi-Yong , Zhang Baoshan , Zheng Anqi , Zhou Tongqing , Zhu Jiang , Mascola John R. , Kwong Peter D. , Nabel Gary J. 
Published: December 2012

ABSTRACTThe outer domain of the HIV-1 gp120 envelope glycoprotein contains the epitope for broadly neutralizing antibodies directed to the CD4-binding site, many of which are able to neutralize over 90% of circulating HIV-1 isolates. While the outer domain is conformationally more stable than other portions of the HIV-1 envelope, efforts to express the outer domain as an immunogen for eliciting broadly neutralizing antibodies have not been successful, potentially because natural outer domain variants do not bind strongly to antibodies such as VRC01. In this study, we optimized the antigenic properties of the HIV-1 Env outer domain to generate OD4.2.2, from the KER2018 strain of clade A HIV-1, enabling it to bind antibodies such as VRC01 with nanomolar affinity. The crystal structure of OD4.2.2 in complex with VRC-PG04 was solved at 3.0-Å resolution and compared to known crystal structures including (i) the structure of core gp120 bound by VRC-PG04 and (ii) a circularly permutated version of the outer domain in complex with antibody PGT128. Much of the VRC-PG04 epitope was preserved in the OD4.2.2 structure, though with altered N and C termini conformations. Overall, roughly one-third of the outer domain structure appeared to be fixed in conformation, independent of alterations in termini, clade, or ligand, while other portions of the outer domain displayed substantial structural malleability. The crystal structure of OD4.2.2 with VRC-PG04 provides atomic-level details for an HIV-1 domain recognized by broadly neutralizing antibodies and insights relevant to the rational design of an immunogen that could elicit such antibodies by vaccination.
Acute liver injury associated with glucosamine dietary supplement
Authors: Ebrahim Vivian , Albeldawi Mazen , Chiang Dian Jung 
Published: December 2012

A 55-year-old woman taking over-the-counter (OTC) glucosamine developed symptomatic hepatotoxicity. Several of her liver enzymes were elevated to 10 times the upper limit of normal. One week after discontinuing glucosamine, serum transaminases fell dramatically, with some returning to normal limits.  Four weeks after glucosamine was discontinued, all her liver tests were normal. Rechallenge was not attempted. The potential causes of hepatocellular injury were evaluated. Glucosamine is a dietary supplement available in a wide variety of commercial preparations, primarily used for joint relief in osteoarthritis. Despite the extensive use of glucosamine supplements, significant elevations of transaminases are rare. The mechanism of hepatotoxicity in many OTC herbal preparations is unknown. It is vital for physicians to elicit a careful history of OTC medications and educate their patients on their potential adverse effects.
Assessing variability in neurointerventional practice patterns for acute ischemic stroke
Authors: Mehta Brijesh , Leslie-Mazwi Thabele M , Chandra Ronil V , Chaudhry Zeshan A , Rabinov James D , Hirsch Joshua A , Schwamm Lee H , Rost Natalia S , Yoo Albert J 
Published: December 2012

BackgroundIntra-arterial therapy (IAT) is increasingly used to treat patients with acute stroke with large vessel occlusions. There are minimal data and guidelines for treatment indications and performance standards. We aimed to gain a better understanding of real-world practice patterns for IAT.MethodsAn internet-based survey was launched to address six specific areas of IAT: practice setting, operator background, operational protocols, quality/safety, decision-making and treatment strategies. The survey invitation was distributed to members of multiple neurointerventional societies.ResultsResponses from 140 neurointerventionalists worldwide were analyzed. The median annual volume of IAT cases per institution was 40, and the median neurointerventional group size was three staff members. Independent predictors of case volume were presence of comprehensive stroke services and telestroke capability. The median minimum National Institutes of Health Stroke Scale score for treatment consideration was 8, although 60% of respondents reported no minimum score cut-off. There was no strict time window from symptom onset to treatment among 41% of respondents for anterior circulation strokes and among 56% for posterior circulation strokes, instead basing treatment decisions on clinical and imaging findings. Despite the emphasis on imaging-based selection, there was pronounced variability in the criteria used. Only 27% used one imaging approach exclusively. IAT following full- or partial-dose intravenous tissue plasminogen activator was performed by 89%. Mechanical devices were the predominant first-line therapy, but specific device usage depended on practice location. Approximately half preferred conscious sedation during IAT.ConclusionsThis survey illustrates significant variation among neurointerventionalists in the real-world use of IAT. Our findings highlight the need for evidence-based practice guidelines.
Challenges faced by trainee psychiatrists working towards competency in psychotherapies
Authors: Parker Stephen , Bylett Margaret , Leggett Andrew 
Published: December 2012

Objective: This paper explores the challenges that trainees of the Royal Australian and New Zealand College of Psychiatrists face as they work towards competency in psychotherapy during basic training. Method: The state of training programs in other countries including the trainee and supervisor perspectives on the outcomes of the shift to competency-based assessment is reviewed, and the limited literature examining the systemic problems impacting on the quality of the training experience in psychotherapies for Australian and New Zealand trainees is considered. Results: The risk of an increasing gap between the ideals and the reality of training expectations and experiences is discussed. Conclusion: The importance of auditing the adherence of training services to College guidelines and formally evaluating the training outcomes in the future is emphasised.
Revocation of Community Treatment Orders in a mental health service network
Authors: Owens Nicholas , Brophy Lisa 
Published: December 2012

Objective: Community Treatment Orders (CTOs) require patients to co-operate with involuntary treatment in the community or risk having their CTO revoked and being readmitted to hospital. CTOs are used frequently in Australia. Their revocation has been under-investigated but is important because of the significant impact this process has on patients, families/carers and service-providers. This paper reports on an investigation of CTO revocations in a Victorian area mental health service in the period 2008–2010. Method: This was a mixed-methods study involving extraction of data from the Victorian statewide clinical database, a file audit and semi-structured group interviews with key stakeholders. Two different time periods were compared. Results: CTOs are commonly revoked within three months of discharge from the inpatient unit and multiple service-providers and family/carers have varying involvement that appears to depend on the timing of the referral to the Crisis Assessment and Treatment Team. Conclusions: The study identified opportunities for improving policy and practice, particularly in relation to reducing the amount of coercion experienced by people on CTOs and improving flexibility of service delivery.
Propensity score matched assessment of treatment patterns and cost of erythropoiesis stimulating agent treatment in patients with cancer receiving myelosuppressive chemotherapy
Authors: Tunceli Ozgur , Bailey Robert A , Stephenson Judith J , Singer Joseph 
Published: December 2012

Objective: To examine epoetin alfa (EPO) and darbepoetin alfa (DARB) treatment patterns and erythropoiesis stimulating agent (ESA) costs in patients with cancer receiving chemotherapy (CRC), and to compare the results observed in the pre-matched total study population (TSP) with a propensity score matched population (PSMP). Methods: A medical claims analysis was conducted from 1 January 2004 through 31 July 2009 using the HealthCore Integrated Research Database. Patients were at least 18 years old, newly initiated on EPO or DARB, received ≥ 2 ESA doses, and had ≥ 1 claim for cancer and chemotherapy proximate to ESA treatment. Patients were matched using propensity scores. January 2010 Wholesale Acquisition Cost was used to calculate drug cost. Mean cumulative ESA dose and drug costs were evaluated in the TSP and PSMP. Results: 4921 EPO and 9173 DARB patients with CRC were identified. In the TSP, mean cumulative ESA doses were EPO: 398,770 units and DARB: 1508 mcg, with similar treatment durations for each. Mean cumulative drug costs were EPO: $6041 and DARB: $7861 (30% higher for DARB). The cumulative dose ratio (EPO units: DARB mcg) was 264:1. The PSMP analysis identified 4831 ESA treated CRC patients in each group. Mean drug costs were EPO: $6055 and DARB: $7863 (30% higher for DARB). The observed dose ratio (EPO units: DARB mcg) was 265:1. Conclusion: In both analyses, the costs of DARB were higher, even after accounting for baseline differences in the PSMP. Similar trends in dose ratios were also observed in both groups.
Unblinding following trial participation: Qualitative study of participants’ perspectives
Authors: Armstrong Natalie , Jackson Clare J , McNicol Sarah , Dixon-Woods Mary , Kenyon Sara , Tarrant Carolyn 
Published: December 2012

Background The implications of offering unblinding to trial participants to treatment arm after trial completion have been little explored. Purpose We sought to explore trial participants’ perspectives on whether they would like to be unblinded as to the treatment arm to which they were allocated following involvement in a large randomised controlled trial (RCT). Methods We conducted semi-structured interviews with 38 women who had participated in a trial during suspected preterm labour and had received the results of a long-term follow-up study that identified adverse outcomes for children in some of the treatment groups. Participants were sampled purposively. Analysis was based on the constant comparative method. Results Most women reported that they wanted to know the treatment arm to which they had been allocated. While the primary motive for some was curiosity, many others wanted to know as part of an attempt to understand or explain their child’s current health problems. These women were motivated by a search for a coherent causal narrative, even though unblinding was unlikely to be able to meet their aspirations. Some participants identified potential disadvantages in discovering their treatment allocation, including feeling responsible for their child’s health status, and some women were very clear that they did not want to know their treatment group. Limitations A purposive sample was used and the extent to which it represents the views of all participants in the study is not established. Conclusions Important challenges arise in offering to unblind trial participants, whatever the trial results. Participants may need help and support to understand the limitations of the knowledge they gain through being unblinded and to decide whether they wish to know to which treatment arm they were allocated.