Clinical Audit of the Radiotherapy Process in Rectal Cancer: Clinical Practice Guidelines and Quality Certification Do Not Avert Variability in Clinical Practice.

BACKGROUND: The therapeutic approach to cancer is complex and multidisciplinary. Radiotherapy is among the essential treatments, whether used alone or in conjunction with other therapies. This study reports a clinical audit of the radiotherapy process to assess the process of care, evaluate adherence to agreed protocols and measure the variability to improve therapeutic quality for rectal cancer. METHODS: Multicentre retrospective cohort study in a representative sample of patients diagnosed with rectal cancer in the Institut Català d'Oncologia, a comprehensive cancer centre with three different settings. We developed a set of indicators to assess the key areas of the radiotherapy process. The clinical audit consisted of a review of a random sample of 40 clinical histories for each centre. RESULTS: The demographic profile, histology and staging of patients were similar between centres. The MRI reports did not include the distance from tumour to mesorectal fascia (rCRM) in 38.3% of the cases. 96.7% of patients received the planned dose, and 57.4% received it at the planned time. Surgery followed neoadjuvant treatment in 96.7% of the patients. Among this group, postoperative CRM was recorded in 65.5% of the cases and was negative in 93.4% of these. With regard to the 34.5% (n = 40) of cases where no CRM value was stated, there were differences between the centres. Mean follow-up was 3.4 (SD 0.6) years, and overall survival at four years was 81.7%. CONCLUSIONS: The audit revealed a suboptimal degree of adherence to clinical practice guidelines. Significant variability between centres exists from a clinical perspective but especially with regard to organization and process.

Clinical usefulness of prognostic biomarkers in optic neuritis.

BACKGROUND AND PURPOSE: Different biological and radiological biomarkers predict clinical conversion to multiple sclerosis (MS) after a clinically isolated syndrome (CIS). The aim was to explore their role in predicting the outcome of patients with optic neuritis (ON), a CIS considered to have a benign prognosis. METHODS: Sixty-eight consecutive ON patients were followed prospectively. Magnetic resonance imaging (MRI) and cerebrospinal fluid studies including oligoclonal immunoglobulin G (IgG) bands (OCGBs), lipid-specific oligoclonal IgM bands (LS-OCMBs) and neurofilament light chain quantification were performed at disease onset. Conversion to clinically definite MS (CDMS) was monitored. RESULTS: The mean time of follow-up of our series was 46.4 months. Twenty-five patients (36.7%) developed CDMS during follow-up. Neurofilament light chain levels did not predict clinical conversion. By contrast, an abnormal MRI increased the risk of CDMS [hazard ratio (HR) 12.5, P = 0.013]. The clearest association was found in patients with more than three T2 lesions. OCGBs also predicted the onset of CDMS (HR 21.3, P = 0.003) and LS-OCMBs were associated with a shorter time to CDMS (HR = 116.6, P < 0.001). CONCLUSIONS: Magnetic resonance imaging and OCGBs predicted conversion to CDMS after an ON episode. In addition, LS-OCMBs identified the ON patients more likely to develop MS early. These results, applicable to the everyday clinical setting, may be of interest for therapeutic decisions.

Natural killer cell subsets in cerebrospinal fluid of patients with multiple sclerosis.

Changes in blood natural killer (NK) cells, important players of the immune innate system, have been described in multiple sclerosis (MS). We studied percentages and total cell counts of different effector and regulatory NK cells in cerebrospinal fluid (CSF) of MS patients and other neurological diseases to gain clearer knowledge of the role of these cells in neuroinflammation. NK cell subsets were assessed by flow cytometry in CSF of 85 consecutive MS patients (33 with active disease and 52 with stable MS), 16 with other inflammatory diseases of the central nervous system (IND) and 17 with non-inflammatory neurological diseases (NIND). MS patients showed a decrease in percentages of different CSF NK subpopulations compared to the NIND group. However, absolute cell counts showed a significant increase of all NK subsets in MS and IND patients, revealing that the decrease in percentages does not reflect a real reduction of these immune cells. Remarkably, MS patients showed a significant increase of regulatory/effector (CD56(bright) /CD56(dim) ) NK ratio compared to IND and NIND groups. In addition, MS activity associated with an expansion of NK T cells. These data show that NK cell subsets do not increase uniformly in all inflammatory neurological disease and suggest strongly that regulatory CD56(bright) and NK T cells may arise in CSF of MS patients as an attempt to counteract the CNS immune activation characteristic of the disease.

Cerebrospinal fluid immunological biomarkers associated with axonal damage in multiple sclerosis.

BACKGROUND AND PURPOSE: Cerebrospinal fluid (CSF) neurofilament light protein (NFL) is a promising biomarker of axonal injury and neurodegeneration. Here CSF lymphocyte subpopulations and antibodies, potential players of neurodegeneration, are examined in relation to CSF NFL shedding in MS. METHODS: Cerebrospinal fluid NFL from 127 consecutive untreated MS patients was analysed. Samples from 37 age-matched patients with other central nervous system non-inflammatory neurological diseases (NIND) were also assessed. CD4+, CD8+, CD56+ and CD19+ cell subsets were studied by flow cytometry. Oligoclonal IgG and IgM bands (OCMB) against lipids were studied by isoelectric focusing and immunoblotting. These data were analysed in relation to clinical and magnetic resonance imaging features. RESULTS: A CSF NFL cut-off value of 900 ng/l (mean + 3 SD of NIND values) was calculated. MS patients with increased NFL values showed significantly higher Multiple Sclerosis Severity Score and magnetic resonance imaging lesion number. The presence of OCMB (P < 0.0001) and elevated T and B lymphocyte counts was associated with increased levels of CSF NFL. CONCLUSIONS: High CSF NFL levels are associated with elevated CSF lymphocyte cell counts and intrathecal synthesis of IgM against lipids. These findings support a role for OCMB in the axonal damage of MS offering a rationale for the association of these antibodies with disability and brain atrophy progression in MS.

CHACO outreach project: the development of a primary health care-based medical genetic service in an Argentinean province.

Dissemination of knowledge in genetics to be applied in medicine has created a growing need for capacity building in health care workers. The CAPABILITY ARGENTINA outreach project protocol was designed as a model to introduce genetics in areas without genetic services. Our aim was for genetic health care to become part of primary care in an Argentine province lacking genetic services. The program was innovative as professionals from the referral center (Garrahan Hospital S.A.M.I.C.) traveled to remote areas to train professionals through problem-based education. A logical framework was designed for a local needs assessment. Teaching materials (Powerpoint presentations, printed syllabus, and CD) and a web page were developed. A demonstration project was carried out in the Province of Chaco, Argentina. A total of 485 health workers were trained. The number of consultations increased significantly in participating areas comparing before and after the training period. To support this increase, a complementary project was set up from a public hospital sponsored from within Argentina to build a cytogenetic laboratory in the capital of the Province of Chaco. The model was improved for reproduction in other areas in Argentina. CAPABILITY ARGENTINA is a capacity building model for training of primary care professionals in genetics that may be applied to other medical specialties. The outcomes of the programme have a direct impact on clinical practice.

Long-term follow-up of radiation accident patients in Peru: review of two cases.

Overexposure to radioactive sources used in radiotherapy or industrial radiography may result in severe health consequences. This report assesses the initial clinical status and the medical and psychological long-term follow-up of two radiation accident patients from Peru during the mid-to-late 1990s: one patient exposed to a radiotherapy (60)Co source in Arequipa, the other patient to a (192)Ir source in Yanango. Commonalities and differences are described. The main causes in both accidents were human error and the failure to apply appropriate safety guidelines and standard operating procedures. Education and training of the personnel working with radiation sources are essential to prevent accidents. The experience gained from the medical management of the two patients is valuable for future treatment of such patients.

Bayesian limits on primordial isotropy breaking.

It is often assumed that primordial perturbations are statistically isotropic, which implies, among other properties, that their power spectrum is invariant under rotations. In this article, we test this assumption by placing bounds on deviations from rotational invariance of the primordial spectrum. Using five-year Wilkinson Microwave Anisotropy Probe cosmic microwave anisotropy maps, we set limits on the overall norm and the amplitude of individual components of the primordial spectrum quadrupole and hexadecapole. We find that there is no significant evidence for primordial isotropy breaking, and constrain the relative contribution of the quadrupole and hexadecapole to be less than, respectively, 23% and 34% at 95% confidence level.

Hepatitis A en la infancia. La punta del iceberg infectológico? / Viral Hepatitis A in childhood. The tip of an infections disease iceberg

The objectives of this study were to analyze the seroepidemiologic prevalence of Hepatitis A Virus (HAV) in children of the city of Resistencia by means of specific antibody detection, relate these data with the socio-sanitary conditions, and discuss vaccine strategies. Two hundred and eighty eight children between 2 and 14 years of age, with a mean of 6.6 years, of both sexes and with no patent liver disease were studied. Blood samples were taken, and the presence of total anti-HAV antibodies was determined. A prevalence of 83.3% was found with no significant differences between sexes. When age groups were compared, antibodies were found in 57.3% of children between 2 and 4 years of age, 90.8% in the 5 to 9 group, and 96.6% in the 10 to 14 group. It was seen that the precarious system of excreta elimination, the lack of potable water in the dwellings, and the absence of sanitary devices, were statistically associated with the high prevalence of HAV infection. In view of the high endemicity found in the first years of life, and considering this disease as a marker of other pathologies with a similar pattern of dissemination, these data may represent the tip of an iceberg holding a broad base of accompanying infections with a high impact in the health of the population. A simultaneous approach towards anti HAV vaccination in young children, and the political decision of improving socio-sanitary conditions and decreasing poverty indexes, should be promptly implemented

Measuring the speed of sound of quintessence.

Quintessence, a time-varying energy component that may account for the accelerated expansion of the universe, can be characterized by its equation of state and sound speed. In this paper, we show that if the quintessence density is at least 1% of the critical density at the surface of last scattering the cosmic microwave background anisotropy can distinguish between models whose sound speed is near the speed of light versus near zero, which could be useful in distinguishing competing candidates for dark energy.

[Hepatitis A in childhood. The tip of an infectious disease iceberg]. / Hepatitis A en la infancia. La punta del iceberg infectológico?

The objectives of this study were to analyze the seroepidemiologic prevalence of Hepatitis A Virus (HAV) in children of the city of Resistencia by means of specific antibody detection, relate these data with the socio-sanitary conditions, and discuss vaccine strategies. Two hundred and eighty eight children between 2 and 14 years of age, with a mean of 6.6 years, of both sexes and with no patent liver disease were studied. Blood samples were taken, and the presence of total anti-HAV antibodies was determined. A prevalence of 83.3% was found with no significant differences between sexes. When age groups were compared, antibodies were found in 57.3% of children between 2 and 4 years of age, 90.8% in the 5 to 9 group, and 96.6% in the 10 to 14 group. It was seen that the precarious system of excreta elimination, the lack of potable water in the dwellings, and the absence of sanitary devices, were statistically associated with the high prevalence of HAV infection. In view of the high endemicity found in the first years of life, and considering this disease as a marker of other pathologies with a similar pattern of dissemination, these data may represent the tip of an iceberg holding a broad base of accompanying infections with a high impact in the health of the population. A simultaneous approach towards anti HAV vaccination in young children, and the political decision of improving socio-sanitary conditions and decreasing poverty indexes, should be promptly implemented.

Dynamical solution to the problem of a small cosmological constant and late-time cosmic acceleration

Increasing evidence suggests that most of the energy density of the universe consists of a dark energy component with negative pressure that causes the cosmic expansion to accelerate. We address why this component comes to dominate the universe only recently. We present a class of theories based on an evolving scalar field where the explanation is based entirely on internal dynamical properties of the solutions. In the theories we consider, the dynamics causes the scalar field to lock automatically into a negative pressure state at the onset of matter domination such that the present epoch is the earliest possible time consistent with nucleosynthesis restrictions when it can start to dominate.

Responses of Antioxidative Systems to Drought Stress in Pendunculate Oak and Maritime Pine as Modulated by Elevated CO2.

The aim of the present study was to investigate the effects of an enhanced CO2 concentration alone or in combination with drought stress on antioxidative systems of a deciduous (oak; Quercus robur) and an evergreen (pine; Pinus pinaster) tree species. The seedlings were grown for one season in a greenhouse in tunnels supplied with 350 or 700 [mu]L L-1 CO2. The experiment was repeated in a second year. Antioxidants, protective enzymes, soluble protein, and pigments showed considerable fluctuations in different years. Elevated CO2 caused significant reductions in the activities of superoxide dismutases in both oak and pine. The activities of ascorbate peroxidase and catalase were also reduced in most cases. The activities of dehydroascorbate reductase, monodehydroascorbate radical reductase, glutathione reductase, and guaiacol peroxidase were affected little or not at all by elevated CO2. When the trees were subjected to drought stress by withholding water, the activities of antioxidative enzymes decreased in leaves of pine and oak grown at ambient CO2 and increased in plants grown at elevated CO2 concentrations. The present results suggest that growth in elevated CO2 might reduce oxidative stress to which leaf tissues are normally exposed and enhance metabolic flexibility to encounter increased stress by increases in antioxidative capacity.

Interactive effects of elevated CO(2) and soil drought on growth and transpiration efficiency and its determinants in two European forest tree species.

The responses of growth and transpiration efficiency (W = biomass accumulation/water consumption) to ambient and elevated atmospheric CO(2) concentrations (350 and 700 micro mol mol(-1), respectively) were investigated under optimal nutrient supply in well-watered and in drought conditions in two temperate-forest tree species: Quercus petraea Liebl. and Pinus pinaster Ait. Under well-watered conditions, doubling the CO(2) concentration for one growing season increased biomass growth by 138% in Q. petraea and by 63% in P. pinaster. In contrast, under drought conditions, elevated CO(2) increased biomass growth by only 47% in Q. petraea and had no significant effect on biomass growth in P. pinaster. Transpiration efficiency was higher in Q. petraea than in P. pinaster in all treatments. This difference was linked (i) to lower carbon isotope discrimination (Delta), and thus lower values of the intercellular/ambient CO(2) concentration (c(i)/c(a)) ratio, in Q. petraea, (ii) to lower values of leaf mass ratio (LMR, leaf mass/whole plant mass), which we suggest was positively related to the proportion of daytime carbon fixation lost by respiration (Phi), in Q. petraea, and (iii) to slightly lower C concentrations in Q. petraea than in P. pinaster. The CO(2)-promoted increase in W was higher in Q. petraea (+80%) than in P. pinaster (+50%), and the difference was associated with a more pronounced decrease in Phi in response to elevated CO(2) in Q. petraea than in P. pinaster, which could be linked with the N dilution effect observed in Q. petraea. Because Phi also directly affects growth, the CO(2)-induced enhancement of Phi in Q. petraea is a crucial determinant of the growth stimulation observed in this species. Leaf gas exchange regulation was not the only factor involved in the responses of growth and W to elevated CO(2) and drought, other physiological processes that have crucial roles include carbon and N allocation and respiration.