High levels of untreated distress and fatigue in cancer patients

The purpose of the study was to assess a large representative sample of cancer patients on distress levels, common psychosocial problems, and awareness and use of psychosocial support services. A total of 3095 patients were assessed over a 4-week period with the Brief Symptom Inventory-18 (BSI-18), a common problems checklist, and on awareness and use of psychosocial resources. Full data was available on 2776 patients. On average, patients were 60 years old, Caucasian (78.3%), and middle class. Approximately, half were attending for follow-up care. Types of cancer varied, with the largest groups being breast (23.5%), prostate (16.9%), colorectal (7.5%), and lung (5.8%) cancer patients. Overall, 37.8% of all patients met criteria for general distress in the clinical range. A higher proportion of men met case criteria for somatisation, and more women for depression. There were no gender differences in anxiety or overall distress severity. Minority patients were more likely to be distressed, as were those with lower income, cancers other than prostate, and those currently on active treatment. Lung, pancreatic, head and neck, Hodgkin's disease, and brain cancer patients were the most distressed. Almost half of all patients who met distress criteria had not sought professional psychosocial support nor did they intend to in the future. In conclusion, distress is very common in cancer patients across diagnoses and across the disease trajectory. Many patients who report high levels of distress are not taking advantage of available supportive resources. Barriers to such use, and factors predicting distress and use of psychosocial care, require further exploration

Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP

Most human protein-encoding genes contain multiple exons that are spliced together, frequently in alternative arrangements, by the spliceosome. It is established that U1 snRNP is an essential component of the spliceosome, in human consisting of RNA and ten proteins, several of which are post- translationally modified and exist as multiple isoforms. Unresolved and challenging to investigate are the effects of these post translational modifications on the dynamics, interactions and stability of the particle. Using mass spectrometry we investigate the composition and dynamics of the native human U1 snRNP and compare native and recombinant complexes to isolate the effects of various subunits and isoforms on the overall stability. Our data reveal differential incorporation of four protein isoforms and dynamic interactions of subunits U1-A, U1-C and Sm-B/B’. Results also show that unstructured post- ranslationally modified C-terminal tails are responsible for the dynamics of Sm-B/B’ and U1-C and that their interactions with the Sm core are controlled by binding to different U1-70k isoforms and their phosphorylation status in vivo. These results therefore provide the important functional link between proteomics and structure as well as insight into the dynamic quaternary structure of the native U1 snRNP important for its function.This work was funded by: BBSRC (OVM), BBSRC and EPSRC (HH and NM), EU Prospects (HH), European Science Foundation (NM), the Royal Society (CVR), and fellowship from JSPS and HFSP (YM and DAPK respectively)

IFNβ Protects Neurons from Damage in a Murine Model of HIV-1 Associated Brain Injury.

Infection with human immunodeficiency virus-1 (HIV-1) causes brain injury. Type I interferons (IFNα/β) are critical mediators of any anti-viral immune response and IFNβ has been implicated in the temporary control of lentiviral infection in the brain. Here we show that transgenic mice expressing HIV-1 envelope glycoprotein 120 in their central nervous system (HIVgp120tg) mount a transient IFNβ response and provide evidence that IFNβ confers neuronal protection against HIVgp120 toxicity. In cerebrocortical cell cultures, neuroprotection by IFNβ against gp120 toxicity is dependent on IFNα receptor 1 (IFNAR1) and the β-chemokine CCL4, as IFNAR1 deficiency and neutralizing antibodies against CCL4, respectively, abolish the neuroprotective effects. We find in vivo that IFNβ mRNA is significantly increased in HIVgp120tg brains at 1.5, but not 3 or 6 months of age. However, a four-week intranasal IFNβ treatment of HIVgp120tg mice starting at 3.5 months of age increases expression of CCL4 and concomitantly protects neuronal dendrites and pre-synaptic terminals in cortex and hippocampus from gp120-induced damage. Moreover, in vivo and in vitro data suggests astrocytes are a major source of IFNβ-induced CCL4. Altogether, our results suggest exogenous IFNβ as a neuroprotective factor that has potential to ameliorate in vivo HIVgp120-induced brain injury

The Impact of Socio-Demographic and Religious Factors upon Sexual Behavior among Ugandan University Students

INTRODUCTION: More knowledge is needed about structural factors in society that affect risky sexual behaviors. Educational institutions such as universities provide an opportune arena for interventions among young people. The aim of this study was to investigate the relationship between sociodemographic and religious factors and their impact on sexual behavior among university students in Uganda. METHODS: In 2005, 980 university students (response rate 80%) were assessed by a self-administered questionnaire. Validated instruments were used to assess socio-demographic and religious factors and sexual behavior. Logistic regression analyses were applied. RESULTS: Our findings indicated that 37% of the male and 49% of the female students had not previously had sex. Of those with sexual experience, 46% of the males and 23% of the females had had three or more sexual partners, and 32% of the males and 38% of the females did not consistently use condoms. For those who rated religion as less important in their family, the probability of early sexual activity and having had a high number of lifetime partners increased by a statistically significant amount (OR = 1.7; 95% CI: 1.2-2.4 and OR = 1.6; 95% CI: 1.1-2.3, respectively). However, the role of religion seemed to have no impact on condom use. Being of Protestant faith interacted with gender: among those who had debuted sexually, Protestant female students were more likely to have had three or more lifetime partners; the opposite was true for Protestant male students. CONCLUSION: Religion emerged as an important determinant of sexual behavior among Ugandan university students. Our findings correlate with the increasing number of conservative religious injunctions against premarital sex directed at young people in many countries with a high burden. of HIV/AIDS. Such influence of religion must be taken into account in order to gain a deeper understanding of the forces that shape sexual behavior in Uganda

New MACRO results on atmospheric neutrino oscillations

The final results of the MACRO experiment on atmospheric neutrino oscillations are presented and discussed. The data concern different event topologies with average neutrino energies of ~3 and ~50 GeV. Multiple Coulomb Scattering of the high energy muons in absorbers was used to estimate the neutrino energy of each event. The angular distributions, the L/E_nu distribution, the particle ratios and the absolute fluxes all favour nu_mu --> nu_tau oscillations with maximal mixing and Delta m^2 =0.0023 eV^2. A discussion is made on the Monte Carlos used for the atmospheric neutrino flux. Some results on neutrino astrophysics are also briefly discussed.Comment: Invited Paper at the NANP03 Int. Conf., Dubna, 200

Final results of magnetic monopole searches with the MACRO experiment

We present the final results obtained by the MACRO experiment in the search for GUT magnetic monopoles in the penetrating cosmic radiation, for the range $4\times 10^{-5}< \beta < 1$. Several searches with all the MACRO sub-detectors (i.e. scintillation counters, limited streamer tubes and nuclear track detectors) were performed, both in stand alone and combined ways. No candidates were detected and a 90% Confidence Level (C.L.) upper limit to the local magnetic monopole flux was set at the level of $1.4\times 10^{-16}$ cm$^{-2}$ s$^{-1}$ sr$^{-1}$. This result is the first experimental limit obtained in direct searches which is well below the Parker bound in the whole $\beta$ range in which GUT magnetic monopoles are expected.Comment: 12 pages, Latex, 9 figures and 2 Table

Nuclearite search with the MACRO detector at Gran Sasso

In this paper we present the results of a search for nuclearites in the penetrating cosmic radiation using the scintillator and track-etch subdetectors of the MACRO apparatus. The analyses cover the beta =v/c range at the detector depth (3700 hg/cm^2) 10^-5 < beta < 1; for beta = 2 x 10^-3 the flux limit is 2.7 x 10^-16 cm^-2 s^-1 sr^-1 for an isotropic flux of nuclearites, and twice this value for a flux of downgoing nuclearites.Comment: 16 pages, 4 Encapsulated Postscript figures, uses article.sty. Submitted to The European Physical Journal

Atmospheric neutrino induced muons in the MACRO detector

A measurement of the flux of neutrino-induced muons using the MACRO detector is presented. Different event topologies, corresponding to different neutrino parent energies can be detected. The upward throughgoing muon sample is the larger event sample. The observed upward-throughgoing muons are 26% fewer than expected and the zenith angle distribution does not fit with the expected one. Assuming neutrino oscillations, both measurements suggest maximum mixing and Dm2 of a few times 10-3 eV2. The other samples are due to the internally produced events and to upward-going stopping muons. These data show a regular deficit of observed events in each angular bin, as expected assuming neutrino oscillations with maximum mixing, in agreement with the analysis of the upward-throughgoing muon sample.Comment: 7 pages 6 figures to appear in the proceedings of XVIII International Conference on Neutrino Physics and Astrophysics (Neutrino'98), Takayama, Japan 4-9 June, 199

Low coverage of intermittent preventive treatment for malaria in pregnancy in Nigeria: demand-side influences

BACKGROUND: Nigeria instituted intermittent preventive treatment for malaria (IPTp) using sulphadoxine-pyrimethamine (SP) for pregnant women in 2001, but coverage remains low. This study examined the influence of demand side factors on IPTp coverage. METHODS: Data were collected using a household survey from 1307 women who were delivered of a live baby within the one-year period preceding the study and through an exit poll from 146 women attending antenatal clinics (ANC). Data analysis examined coverage based on the national and WHO guidelines for IPTp delivery which differ with regards to use of IPTp in the last month of pregnancy. Focus group discussions (FGDs) were undertaken to further explain demand side constraints to coverage. RESULTS: From the household survey, 96.1% of respondents attended ANC, with most having five or more visits. Overall IPTp coverage for the first and second doses was 13.7% and 7.3% respectively. The coverage was higher in the urban areas compared to rural areas (p < 0.01). Amongst women who could have received IPTp based on the timing of their attendance, only 14.1% and 14.3% were offered the first dose based on national and WHO guidelines, while 7.7% and 7.5% were offered the second dose respectively giving significant missed opportunities. Amongst ANC attendees offered first and second doses, 98.9% and 96.9% respectively took the medicine. Only 13.6% and 21.5% of these clients reported taking the drug under direct observation. The low level of coverage was confirmed by exit survey data, which found coverage of 11.6% and 3.0% for the first and second doses. The FGDs revealed that women do not have many concerns about side effects, but they take drugs providers give them because they believe such drugs must be safe. CONCLUSION: This study found low coverage of IPTp and high levels of missed opportunities supporting findings that high ANC attendance does not guarantee high IPTp coverage. Demand side factors such as ANC attendance, appropriate timing of attendance, and perceptions about side effects were not constraining factors to increased coverage, raising the need to examine supply side factors

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD