710 research outputs found
A bi-dimensional finite mixture model for longitudinal data subject to dropout
In longitudinal studies, subjects may be lost to follow-up, or miss some of
the planned visits, leading to incomplete response sequences. When the
probability of non-response, conditional on the available covariates and the
observed responses, still depends on unobserved outcomes, the dropout mechanism
is said to be non ignorable. A common objective is to build a reliable
association structure to account for dependence between the longitudinal and
the dropout processes. Starting from the existing literature, we introduce a
random coefficient based dropout model where the association between outcomes
is modeled through discrete latent effects. These effects are outcome-specific
and account for heterogeneity in the univariate profiles. Dependence between
profiles is introduced by using a bi-dimensional representation for the
corresponding distribution. In this way, we define a flexible latent class
structure which allows to efficiently describe both dependence within the two
margins of interest and dependence between them. By using this representation
we show that, unlike standard (unidimensional) finite mixture models, the non
ignorable dropout model properly nests its ignorable counterpart. We detail the
proposed modeling approach by analyzing data from a longitudinal study on the
dynamics of cognitive functioning in the elderly. Further, the effects of
assumptions about non ignorability of the dropout process on model parameter
estimates are (locally) investigated using the index of (local) sensitivity to
non-ignorability
De novo rational design of a freestanding, supercharged polypeptide, proton-conducting membrane
Proton translocation enables important processes in nature and man-made technologies. However, controlling proton conduction and fabrication of devices exploiting biomaterials remains a challenge. Even more difficult is the design of protein-based bulk materials without any functional starting scaffold for further optimization. Here, we show the rational design of proton-conducting, protein materials exceeding reported proteinaceous systems. The carboxylic acid-rich structures were evolved step by step by exploring various sequences from intrinsically disordered coils over supercharged nanobarrels to hierarchically spider β sheet containing protein-supercharged polypeptide chimeras. The latter material is characterized by interconnected β sheet nanodomains decorated on their surface by carboxylic acid groups, forming self-supportive membranes and allowing for proton conduction in the hydrated state. The membranes showed an extraordinary proton conductivity of 18.5 ± 5 mS/cm at RH = 90%, one magnitude higher than other protein devices. This design paradigm offers great potential for bioprotonic device fabrication interfacing artificial and biological systems
Independent Eigenstates of Angular Momentum in a Quantum N-body System
The global rotational degrees of freedom in the Schr\"{o}dinger equation for
an -body system are completely separated from the internal ones. After
removing the motion of center of mass, we find a complete set of
independent base functions with the angular momentum . These are
homogeneous polynomials in the components of the coordinate vectors and the
solutions of the Laplace equation, where the Euler angles do not appear
explicitly. Any function with given angular momentum and given parity in the
system can be expanded with respect to the base functions, where the
coefficients are the functions of the internal variables. With the right choice
of the base functions and the internal variables, we explicitly establish the
equations for those functions. Only (3N-6) internal variables are involved both
in the functions and in the equations. The permutation symmetry of the wave
functions for identical particles is discussed.Comment: 24 pages, no figure, one Table, RevTex, Will be published in Phys.
Rev. A 64, 0421xx (Oct. 2001
Estimating the incidence of acute infectious intestinal disease in the community in the UK:A retrospective telephone survey
Objectives: To estimate the burden of intestinal infectious disease (IID) in the UK and determine whether disease burden estimations using a retrospective study design differ from those using a prospective study design. Design/Setting: A retrospective telephone survey undertaken in each of the four countries comprising the United Kingdom. Participants were randomly asked about illness either in the past 7 or 28 days. Participants: 14,813 individuals for all of whom we had a legible recording of their agreement to participate Outcomes: Self-reported IID, defined as loose stools or clinically significant vomiting lasting less than two weeks, in the absence of a known non-infectious cause. Results: The rate of self-reported IID varied substantially depending on whether asked for illness in the previous 7 or 28 days. After standardising for age and sex, and adjusting for the number of interviews completed each month and the relative size of each UK country, the estimated rate of IID in the 7-day recall group was 1,530 cases per 1,000 person-years (95% CI: 1135 – 2113), while in the 28-day recall group it was 533 cases per 1,000 person-years (95% CI: 377 – 778). There was no significant variation in rates between the four countries. Rates in this study were also higher than in a related prospective study undertaken at the same time. Conclusions: The estimated burden of disease from IID varied dramatically depending on study design. Retrospective studies of IID give higher estimates of disease burden than prospective studies. Of retrospective studies longer recall periods give lower estimated rates than studies with short recall periods. Caution needs to be exercised when comparing studies of self-reported IID as small changes in study design or case definition can markedly affect estimated rates
Photo- and Electro-Disintegration of 3He at Threshold and pd Radiative Capture
The present work reports results for: pd radiative capture observables
measured at center-of-mass (c.m.) energies in the range 0--100 keV and at 2 MeV
by the TUNL and Wisconsin groups, respectively; contributions to the
Gerasimov-Drell-Hearn (GDH) integral in 3He from the two- up to the three-body
breakup thresholds, compared to experimental determinations by the TUNL group
in this threshold region; longitudinal, transverse, and interference response
functions measured in inclusive polarized electron scattering off polarized 3He
at excitation energies below the threshold for breakup into ppn, compared to
unpolarized longitudinal and transverse data from the Saskatoon group. The
calculations are based on a realistic Hamiltonian with two- and three-nucleon
interactions and a realistic current operator, including one- and two-body
components. The theoretical predictions obtained by including only one-body
currents are in violent disagreement with data. These differences between
theory and experiment are, to a large extent, removed when two-body currents
are taken into account, although some rather large discrepancies remain in the
c.m. energy range 0--100 keV, particularly for the pd differential cross
section and tensor analyzing power at small angles, and contributions to the
GDH integral. A rather detailed analysis indicates that these discrepancies
have, in large part, a common origin, and can be traced back to an excess
strength obtained in the theoretical calculation of the E1 reduced matrix
element associated with the pd channel having L,S,J=1,1/2,3/2. It is suggested
that this lack of E1 strength observed experimentally might have implications
for the nuclear interaction at very low energies. Finally, the validity of the
long-wavelength approximation for electric dipole transitions is discussed.Comment: 47 pages RevTex file, 10 PostScript figures, submitted to Phys. Rev.
Electron and Photon Scattering on Three-Nucleon Bound States
A big spectrum of processes induced by real and virtual photons on the 3He
and 3H nuclei is theoretically investigated through many examples based on
nonrelativistic Faddeev calculations for bound and continuum states. The modern
nucleon-nucleon potential AV18 together with the three-nucleon force UrbanaIX
is used. The single nucleon current is augmented by explicit pi- and rho-like
two-body currents which fulfill the current continuity equation together with
the corresponding parts of the AV18 potential. We also employ the Siegert
theorem, which induces many-body contributions to the current operator. The
interplay of these different dynamical ingredients in the various
electromagnetic processes is studied and the theory is compared to the
experimental data. Overall we find fair to good agreement but also cases of
strong disagreement between theory and experiment, which calls for improved
dynamics. In several cases we refer the reader to the work of other groups and
compare their results with ours. In addition we list a number of predictions
for observables in different processes which would challenge this dynamical
scenario even more stringently and systematically.Comment: 154 pages, 80 figures includes as ps files, 21 additional figures as
jpeg file
Interleukin-6 gene (IL-6): a possible role in brain morphology in the healthy adult brain
Background: Cytokines such as interleukin 6 (IL-6) have been implicated in dual functions in neuropsychiatric disorders. Little is known about the genetic predisposition to neurodegenerative and neuroproliferative properties of cytokine genes. In this study the potential dual role of several IL-6 polymorphisms in brain morphology is investigated. Methodology: In a large sample of healthy individuals (N = 303), associations between genetic variants of IL-6 (rs1800795; rs1800796, rs2069833, rs2069840) and brain volume (gray matter volume) were analyzed using voxel-based morphometry (VBM). Selection of single nucleotide polymorphisms (SNPs) followed a tagging SNP approach (e.g., Stampa algorigthm), yielding a capture 97.08% of the variation in the IL-6 gene using four tagging SNPs. Principal findings/results: In a whole-brain analysis, the polymorphism rs1800795 (−174 C/G) showed a strong main effect of genotype (43 CC vs. 150 CG vs. 100 GG; x = 24, y = −10, z = −15; F(2,286) = 8.54, puncorrected = 0.0002; pAlphaSim-corrected = 0.002; cluster size k = 577) within the right hippocampus head. Homozygous carriers of the G-allele had significantly larger hippocampus gray matter volumes compared to heterozygous subjects. None of the other investigated SNPs showed a significant association with grey matter volume in whole-brain analyses. Conclusions/significance: These findings suggest a possible neuroprotective role of the G-allele of the SNP rs1800795 on hippocampal volumes. Studies on the role of this SNP in psychiatric populations and especially in those with an affected hippocampus (e.g., by maltreatment, stress) are warranted.Bernhard T Baune, Carsten Konrad, Dominik Grotegerd, Thomas Suslow, Eva Birosova, Patricia Ohrmann, Jochen Bauer, Volker Arolt, Walter Heindel, Katharina Domschke, Sonja Schöning, Astrid V Rauch, Christina Uhlmann, Harald Kugel and Udo Dannlowsk
A cluster of Candida krusei infections in a haematological unit
<p>Abstract</p> <p>Background</p> <p><it>Candida krusei </it>infections are associated with high mortality. In order to explore ways to prevent these infections, we investigated potential routes for nosocomial spread and possible clonality of <it>C. krusei </it>in a haematological unit which had experienced an unusually high incidence of cases.</p> <p>Methods</p> <p>We searched for <it>C. krusei </it>contamination of the hospital environment and determined the level of colonization in patients and health care workers. We also analyzed the possible association between exposure to prophylactic antifungals or chemotherapeutic agents and occurrence of <it>C. krusei</it>. The <it>C. krusei </it>isolates found were genotyped by pulsed-field electrophoresis method in order to determine possible relatedness of the cases.</p> <p>Results</p> <p>Twelve patients with invasive <it>C. krusei </it>infection and ten patients with potentially significant infection or mucosal colonization were documented within nine months. We were unable to identify any exogenic source of infection or colonization. Genetic analysis of the isolates showed little evidence of clonal transmission of <it>C. krusei </it>strains between the patients. Instead, each patient was colonized or infected by several different closely related genotypes. No association between medications and occurrence of <it>C. krusei </it>was found.</p> <p>Conclusion</p> <p>Little evidence of nosocomial spread of a single <it>C. krusei </it>clone was found. The outbreak may have been controlled by cessation of prophylactic antifungals and by intensifying infection control measures, e.g. hand hygiene and cohorting of the patients, although no clear association with these factors was demonstrated.</p
Gonadal function in male patients after treatment for malignant lymphomas, with emphasis on chemotherapy
Gonadal function was assessed in male lymphoma survivors based on serum hormone levels (LH, FSH, testosterone, SHBG), and was related to treatment, age and observation time. Male patients ⩽50 years at diagnosis treated for Hodgkin's (HL) and/or non-Hodgkin's lymphoma (NHL) at the Norwegian Radium Hospital from 1 January 1980 to 31 December 2002 were included. Five treatment groups were defined: 1: radiotherapy only and/or low gonadotoxic chemotherapy (both HL and NHL)(‘No/low'), 2: medium gonadotoxicity chemotherapy for NHL (‘med-NHL'), 3: medium gonadotoxicity chemotherapy for HL (‘med-HL'), 4: highly gonadotoxic chemotherapy for NHL (‘high-NHL'), 5: highly gonadotoxic chemotherapy for HL (‘high-HL'). Gonadal hormone levels were categorised into three groups: 1: All gonadal hormones within normal range (normal), 2: Isolated elevated FSH, with LH, SHBG and testosterone within normal range (exocrine hypogonadism), 3: Testosterone below and/or LH above normal range (endocrine hypogonadism). One hundred and forty-four (49%) of the patients had normal gonadal hormones, 60 (20%) displayed exocrine hypogonadism and almost one-third (n=90, 30%) had endocrine hypogonadism. Compared to those treated with no/low gonadotoxic chemotherapy patients from all other treatment groups had significantly elevated risk for exocrine hypogonadism. Patients from the other treatment groups, except those in the med-NHL group, also had significantly elevated risk for endocrine hypogonadism compared with the group treated with no/low gonadotoxic chemotherapy. Men aged above 50 years at survey were about five times more likely to have endocrine hypogonadism compared with those less than 40 years. Because of the adverse health effects following long-lasting endocrine hypogonadism, gonadal hormones should be assessed regularly in male lymphoma survivors, especially after treatment with alkylating agents and high-dose chemotherapy with autologous stem cell support and in male patients who are 50 years and older
Histone deacetylase inhibitors in Hodgkin lymphoma
Although Hodgkin lymphoma (HL) is considered one of the most curable human cancers, the treatment of patients with relapsed and refractory disease, especially those who relapse after autologous stem cell transplantation, remains challenging. Furthermore, because of the young age of these patients, the impact of early mortality on the number of years lost from productive life is remarkable. Patients with relapsed HL post stem cell transplantation currently have no curative therapy, and are in need for new drugs and novel treatment strategies. While no new drugs have been approved for the treatment of patients with HL in more than three decades, several new agents are demonstrating promising results in early clinical trials. This review will focus on the emerging role of histone deacetylase inhibitors in patients with relapsed HL
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