Testing Strong Field QED Close to the Fully Nonperturbative Regime Using Aligned Crystals.

Processes occurring in the strong field regime of QED are characterized by background electromagnetic fields of the order of the critical field F_{cr}=m^{2}c^{3}/ℏ|e| in the rest frame of participating charges. It has been conjectured that if in their rest frame electrons and positrons experience field strengths of the order of F_{cr}/α^{3/2}≈1600F_{cr}, with α≈1/137 being the fine-structure constant, their effective coupling with radiation becomes of the order of unity. Here we show that channeling radiation by ultrarelativistic electrons with energies of the order of a few TeV on thin tungsten crystals allows us to test the predictions of QED close to this fully nonperturbative regime by measuring the angularly resolved single photon intensity spectrum. The proposed setup features the unique characteristics that essentially all electrons (1) undergo at most a single photon emission and (2) experience at the moment of emission and in the angular region of interest the maximum allowed value of the field strength, which at 2 TeV exceeds F_{cr} by more than 2 orders of magnitude in their rest frame.

Plasma-based generation and control of a single few-cycle high-energy ultrahigh-intensity laser pulse.

A laser-boosted relativistic solid-density paraboloidal foil is known to efficiently reflect and focus a counterpropagating laser pulse. Here we show that in the case of an ultrarelativistic counterpropagating pulse, a high-energy and ultrahigh-intensity reflected pulse can be more effectively generated by a relatively slow and heavy foil than by a fast and light one. This counterintuitive result is explained with the larger reflectivity of a heavy foil, which compensates for its lower relativistic Doppler factor. Moreover, since the counterpropagating pulse is ultrarelativistic, the foil is abruptly dispersed and only the first few cycles of the counterpropagating pulse are reflected. Our multidimensional particle-in-cell simulations show that even few-cycle counterpropagating laser pulses can be further shortened (both temporally and in the number of laser cycles) with pulse amplification. A single few-cycle, multipetawatt laser pulse with several joules of energy and with a peak intensity exceeding 10(23) W/cm(2) can be generated already employing next-generation high-power laser systems. In addition, the carrier-envelope phase of the generated few-cycle pulse can be tuned provided that the carrier-envelope phase of the initial counterpropagating pulse is controlled.

Phenomenology and emotional impact of neuropsychiatric symptoms in orthotopic liver transplant for hepatocellular carcinoma.

BACKGROUND: Few studies have focused on neuropsychiatric symptoms like hallucinations or delusions occurring in the early posttransplant period. The aim of this study was to estimate the percentage of patients reporting neuropsychiatric symptoms in the immediate postoperative phase, to describe the phenomenology, and to evaluate the emotional impact of such disorders. METHOD: We studied 94 consecutive patients who underwent orthotopic liver transplant (OLT) for hepatocellular carcinoma at least 30 days prior. The presence of neuropsychiatric symptoms were retrospectively evaluated through a semistructured interview. RESULTS: Overall 49 patients (52%) reported various postoperative neuropsychiatric symptoms. None of the demographic and clinical variables showed significant associations, except for barbiturate administration; patients using barbiturates showed a lower percentage of neuropsychiatric symptoms. It was a time-limited phenomenon that in most cases resolved by day 7 after transplantation. Interestingly, the most frequent emotion perceived was surprise and not fear; a nontrivial amount of patients reported happiness, while many patients reported no emotion. CONCLUSIONS: The results of this study suggested the usefulness of a registry of the neurological and psychiatric complications after OLT that may help to clarify the pathogenic mechanisms of such complications and implement uniform protocols of prevention and treatment. In fact, better knowledge of the phenomenology of neuropsychiatric symptoms in OLT recipients could allow easier symptom recognition and therapy adjustments on the basis of the emotional impact of such symptoms on patients, family, and caregivers, as well as increase patients' awareness and capability to face this experience.

Ease-of-use protocol for the rapid detection of third-generation cephalosporin resistance in Enterobacteriaceae isolated from blood cultures using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry.

An ease-of-use protocol for the identification of resistance against third-generation cephalosporins in Enterobacteriaceae isolated from blood culture bottles was evaluated using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. A cefotaxime hydrolysis assay from chocolate agar subcultures using antibiotic discs and without inoculum standardization was developed for routine work flow, with minimal hands-on time. This assay showed good performance in distinguishing between cefotaxime-susceptible and cefotaxime-resistant strains, with excellent results for Escherichia coli (sensitivity 94.7%, specificity 100%). However, cefotaxime resistance was not detected reliably in Enterobacteriaceae expressing AmpC genes or carbapenemase-producing Klebsiella pneumoniae.

Immunological activation markers in the serum of African and European HIV-seropositive and seronegative individuals.

OBJECTIVE: The concentration of type 1 and type 2 cytokines and fibroblast-associated apoptosis-1 soluble receptor (sAPO-1/Fas) was analysed in the sera of Ugandan and Italian HIV-1-seropositive and seronegative individuals. The data were compared to determine whether the immunological status of these groups was different. METHODS: Sixty-seven Ugandan and 30 Italian HIV-positive patients were analysed and stratified according to CD4 counts (group 1, > 500 x 10(6)/l; group 2, 200-500 x 10(6)/l; group 3, < 200 x 10(6)/l). Sera from 15 Ugandan and 11 Italian HIV-negative blood donors were also analysed. Serum concentration of type 1 cytokines [interleukin (IL)-2, IL-12, and interferon (IFN)-gamma] and type 2 cytokines (IL-4 and IL-10), and sAPO-1/Fas were measured by enzyme-linked immunosorbent assay. RESULTS: Serum levels of IL-2, IFN-gamma and IL-10 but not of IL-4 and IL-12, were elevated in HIV-positive group 1 and 2 Africans compared with HIV-positive Italian individuals. IL-4 was mildly augmented in HIV-positive group 3 African patients. Serum concentration of sAPO-1/Fas was reduced in HIV-positive Africans compared with HIV-positive Italian individuals. Finally, serum levels of IL-2 and IL-10 were increased and sAPO-1/Fas reduced when sera of HIV-negative African healthy controls were compared with their Italian counterparts. The ratio of type 1/type 2 cytokines was roughly 1.0 in HIV-negative African controls, and much greater than 1.0 in HIV-negative Italian controls. CONCLUSIONS: These preliminary findings indicate that immune activation is present in African HIV infection. Furthermore, these data raise the possibility that abnormal immune activation and increased susceptibility to antigen-induced cell death is present even in HIV-negative African controls.

Karnofsky and ECOG performance status scoring in lung cancer: a prospective, longitudinal study of 536 patients from a single institution.

The Karnofsky's index of performance status (KPS) and the Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS) are widely used methods of assessing the functional status of cancer patients. In this study, we compare their predictive validity, and suggest a table of transformation between scales. 536 consecutive lung cancer patients were assigned both KPS and ECOG PS scores before, during and after treatment (in all, 1656 assignments). Patients were accurately staged at diagnosis, and carefully re-evaluated at each follow-up visit. Multiple clinical, laboratory and instrumental data were recorded along with performance status assessments. Survival times were measured from the pathological diagnosis. KPS and ECOG PS assignments were strongly related to each other (Spearman R = -0.869). Correlation between scales persisted unchanged in pretreatment and post-treatment assessments, advanced and limited diseases, response or non-response to treatment, and different assessors (R indices ranging from -0.825 to -0.901). A three-point conversion table showed the highest rate of success with an overall percentage of agreement exceeding 84% (grade 1: KPS = 100, 90, 80 and ECOG PS = 0, 1; grade 2: KPS = 70, 60 and ECOG PS = 2; grade 3: KPS < 60 and ECOG PS = 3, 4). Both univariate and multivariate analyses of survival documented the predictive validity of the two scales. However, KPS showed less ability than ECOG PS to discriminate patients with different prognosis. Because of the better predictive ability shown in this study, ECOG PS should be preferred to KPS. A general consensus on the scale to use could avoid problems of conversion, which is not always easy and free of errors.

Effect of home care on the place of death of advanced cancer patients.

This study presents a prospective evaluation of the home care programme for patients with advanced cancer at the National Cancer Institute of Milan. Demographic, psychosocial and physical variables were evaluated. The Therapy Impact Questionnaire was used for symptom and quality of life assessment. The association of clinical and demographic variables with the place of death was investigated, considering that the aim of the home care programme is to follow up patients until death in their houses. Eighty-six per cent (86%) of patients died at home and 14% in hospitals. Multivariate analysis showed that only a higher degree of family support was associated with home death. Several changes in symptoms and quality of life items scores were seen, pain improved while physical debility and cognitive functions worsened throughout the home care duration to death. High intensity pain and dyspnoea were still present in, respectively, 23.8 and 15.3% of patients in the last week of life. Psychological distress was high at the end of life and did not seem to be affected by treatment. Home care is a feasible alternative for implementing palliative care in a selected population of patients with advanced cancer. Palliation of physical symptoms is more easily achieved than the control of psychological suffering. Family and economical issues implied by home care models should be part of the discussion in implementing palliative care for advanced cancer patients.

HCV and tumors correlated with immune system: a case-control study in an area of hyperendemicity.

Hepatitis C virus (HCV) is a RNA virus that cannot be integrated with the host genome; it can, however, exert its oncogenetic potential indirectly by contributing to the modulator effects of the host immune system, probably through a capacity to elude the immune system. We have carried out a case controlled study on tumors correlated with the immune system (multiple myeloma, non-Hodgkin lymphoma and Hodgkin disease) and HCV, in a high prevalence area. The relationship between each cancer and HCV infection was assessed by means of odds ratios (ORs) and corresponding 95% confidence intervals. Risks were greater for B-cell non-Hodgkin lymphoma (OR=3.7, 95%CI, 1.9-7.4, P=0.0001) and multiple myeloma (OR=4.5, 95%CI, 1.9-10.7, P=0.0004). Our study is particularly important for public health, since it shows that during the coming years in the South of Italy, because of the high prevalence of HCV, there are good reasons to expect not only an increase of liver cancer, but also an increased incidence of great number of tumors correlated with the immune system.

The patient's perception of his own quality of life might have an adjunctive prognostic significance in lung cancer.

Only 5-10% of patients with lung cancer (LC) can be expected to be cured by radical treatments. In the remaining subjects the potential survival benefit of treatment must be weighed, taking into consideration the possible deterioration of quality of life (QL). Indeed, studies dealing with different aspects of QL are being increasingly reported in LC. In a few of them, the interesting observation was made that the patient-rated QL correlated well with the subsequent clinical outcome. In the present study we analyse 11 items of the Therapy Impact Questionnaire (a new instrument of QL), assessing both disease and therapy impact on physical condition, functional status, concomitant emotional and cognitive factors and social interactions. Questionnaires were completed by 128 consecutive LC patients, who had been seen, in the years 1990 through 1993, either for a newly diagnosed cancer (40 patients), or after a successful operation (15 patients), or during active and/or symptomatic treatment (73 patients). At the time of the QL assessment, a minimal set of demographic and clinical variables was recorded. Univariate tests of survival showed that stage of disease, difficulty at work or doing the housework, weight loss, performance status, difficulty relaxing, having been felt unsure, and tumor cell type were all associated, in decreasing order of significance, with prognosis. QL variables correlated well with each other, but poorly with clinical and demographic variables (an expected exception was the good correlation existing between working capacity/physical autonomy and the corresponding observer evaluation of performance status). This lack of correlations explains how QL variables maintained their significance in multivariate survival analyses. In the best multivariate model, the self-estimated difficulty at work or doing the housework followed the stage of disease, but preceded weight loss as a significant, independent, prognostic determinant. Further studies evaluating several other additional prognostic indicators are needed to better clarify the relative prognostic importance of quality of life.

Trazodone for deafferentation pain. Comparison with amitriptyline.

We report a clinical multicentre experience with antidepressant agents (trazodone and amitriptyline) in the treatment of chronic pain due to deafferentation. Forty five patients were admitted to the study; most of them with oncological peripheral nerve lesions. Almost all of them were already being treated with NSAID in association with weak or strong opioids. A random double blind study was performed: 23 patients were treated with trazodone, 22 with amitriptyline. In the assessment of results, pain intensity, hours of sleep, hours standing and lying, side effects, mood, anxiety and weakness were all taken into consideration. The therapeutic analgesic efficacy of the two drugs proved to be similar.

Human B-cell lymphoma in severe combined immunodeficient mice after active infection with Epstein-Barr virus.

BACKGROUND: B-cell lymphomas (BCL) occur with increased frequency in immunosuppressed patients. BCL develop in severe combined immunodeficient (SCID) mice after engraftment with human peripheral blood leukocytes (PBL; hu-PBL-SCID mice) and infection with Epstein-Barr virus (EBV). The contributions of latent and active EBV infection to BCL development, the potential enhancing effects of immunosuppressive therapy, and inhibitory effects of antiviral therapy on the development of BCL in this model were studied. METHODS: SCID mice were engrafted with PBL from EBV-seropositive donors (latent infection), PBL from EBV-seronegative donors followed by infection with EBV (active infection), PBL from EBV-seropositive donors followed by infection with EBV (latent plus active infection), or EBV-transformed B-lymphoblastoid cells and monitored for the development of BCL. Hu-PBL-SCID mice were treated with the immunosuppressive agents cyclosporine or methylprednisolone or the antiviral agents acyclovir or ganciclovir. RESULTS: Tumors developing in hu-PBL-SCID mice were high-grade lymphomas of human B-cell origin and contained EBV-DNA. BCL developed in 70% of mice 11 to 14 weeks after latent infection. BCL developed after 4 to 7 weeks in all hu-PBL-SCID mice after active infection. Treatment with cyclosporine or methylprednisolone had no effect on BCL development after active infection, but inhibited rather than enhanced the development of BCL in latently infected mice. Ganciclovir, but not acyclovir, inhibited BCL development after active infection. CONCLUSIONS: The hu-PBL-SCID mouse provides an in vivo model of BCL associated with immunosuppression. Active EBV infection results in the rapid development of BCL in this model even when latently infected B cells are present. Inhibition of BCL development in latently infected hu-PBL-SCID mice by immunosuppressive therapy may reflect inhibition of a T-cell/B-cell interaction necessary for B-cell activation. Inhibition of BCL development by granciclovir suggests a possible role for this agent in the management of BCL associated with immunosuppression.

Determinant factors for diagnostic delay in operable breast cancer patients.

Randomized trials of mammographic screening have provided strong evidence that early diagnosis and treatment of breast cancer can reduce the specific mortality. Moreover, in a recent systematic review of published studies, delays of 3-6 months between symptom onset and treatment have been clearly found to be associated with lower survival rates for breast cancer patients. The aim of this study was to examine delays registered among breast cancer patients in southern Italy, in order to recognize their determining factors so as to provide women with a better opportunity for survival. The variables examined were age (< 50, 50-64, > or = 65 years), education (< or = 5, > 5 school years); symptom status at first presentation (symptomatic or asymptomatic); date of first symptom presentation; date of first consultation with a health provider; the type of health provider consulted; tumour size and nodal status according to the pTNM system. Time intervals were categorized into: < 1 month, 1-3 months and > 3 months for patient and medical delay; 1-3 months, 3-6 months, > 6 months for overall delay. Patient delay was associated with age and education: a higher risk was found for women of over 65 years age (odds ratio (OR) 2.1, 95% confidence interval (CI) 1.2-3.5) and with < or = 5 years school attendance (OR 3.3, 95% CI 2.0-5.6). Medical delay was seen to be associated with the professional figure: significant differences were found between senologists (oncologists exclusively dedicated to breast cancer operation) and other specialists (OR 3.5, 95% CI 1.5-8.4). Young age and symptomatic presentation were found to be high risk factors. Concerning tumour size in overall delay, in cases where the tumour was > 2 cm the OR was 2.4 (95% CI 1.5-3.7). Our study suggests that diagnostic delay can be reduced by providing more efficient training programmes for members of the medical profession and by producing educational training programmes targeted specifically at each age category (i.e. in older women more attention to education in prevention; in younger women correct information about mammography and specialized structures).

Prognostic value of quality of life scores in terminal cancer patients.

A multicenter cross-sectional study of 115 terminal cancer patients in eight home-care units assessed the prognostic value of quality of life scores, as measured by the Therapy Impact Questionnaire (TIQ). The analysis of the questionnaires completed by 100 patients revealed an association between survival and many of the scales: fatigue, gastrointestinal symptoms, global health status, functional impairment, emotional status, and cognitive status. This association was also observed for some specific physical symptoms, such as confusion, weakness, and loss of appetite, and the overall number of symptoms reported by the patient. Adjusting for some possible confounding factors, only confusion (among the physical symptoms), cognitive status, and global health status (among TIQ primary scales) showed independent prognostic value. As regards the latter two scales, median survival time was distributed differently for patients with no impairment of either (137 days), with impairment of one scale (50 days) and with impairment of both scales (17 days). The judgment expressed by the patient about subjective perception of general malaise and cognitive difficulties can give the clinician important prognostic information.

Italian consensus on a curriculum for volunteer training in oncology.

Volunteers' education, together with selection and organization, are fundamental for an adequate volunteer service in oncology, which is focused on patient and family needs and is fully integrated with the activity of the care team. To achieve such an aim, well-defined requirements and educational objectives are essential. A curriculum for voluntary service in oncology was developed through a consensus of experts. By comparing the work carried out by six different teams, a questionnaire was drafted, which grouped 91 educational aims. For each, the questionnaire queried whether the aim was relevant or not, and, if yes, whether it should be pursued through (a) knowledge, (b) skill, and/or (c) attitude (with a possible multiple answer). To improve comprehension, the questionnaire was divided into five sections: (a) the association; (b) the disease, therapies, and care site; (c) voluntary service in oncology; (d) psychosocial aspects of the patient and family; and (e) approach, communication, and acceptance. The questionnaire was sent to 117 delegates from 93 Italian volunteer organizations who, during a period of 8 years, had attended a course for volunteer trainers held by the Italian League Against Cancer. As indicated in the letter forwarded with the questionnaire, the final document would report only the aims considered relevant by at least 70% of the participants. Moreover, the area(s) of pursuit (knowledge, skill, and attitude) would be stated for each goal when indicated by at least one-half of the participants. Of 117 individuals questioned, 83 (71%) replied. Of the 91 aims proposed, 60 were considered relevant, and a type of approach (knowledge, skill, and/or attitude) was suggested. The formative curriculum of voluntary service in oncology represents a consensual guideline for future training programs.

Characteristics of terminal cancer patients who committed suicide during a home palliative care program.

Cancer patients may commit suicide at any stage of the disease and many risk factors of suicide have been described in the literature. To identify the possible vulnerability factors of suicide in five terminal cancer patients who committed suicide while they were cared for at home by well-trained palliative care teams, a psychological autopsy study was carried out by reviewing their medical records; their report of symptoms at the time of care; and with the caregivers', doctors', and nurses' recollection of events by means of a structured interview prepared ad hoc. We collected data regarding the physical, emotional, and social suffering of the patients, their personality profile, and their feelings with respect to the illness and disability. The interviews lasted for a mean of two hours and were performed from 2-8 years after the suicide events by the social worker at the Rehabilitation and Palliative Care Division. The interviews took place between June 1996 and January 1998. All the patients showed great concern about the lack of autonomy and independence, refused dependence on others and had fear/worry of losing their autonomy. Four patients presented functional and physical impairments, uncontrolled pain, awareness of being in the terminal stage, and mild to moderate depression. They had a feeling of hopelessness consequent to their clinical conditions, fear of suffering, and feeling of being a burden on others. They had a strong character and managerial professions. They had isolated themselves from others and they had previously talked about suicide. Before committing suicide, three patients had adverse physical/emotional consequences to the oncological treatments-they showed aggressiveness towards their family and one towards the home care physician. Multiple vulnerability factors were present simultaneously in all patients. However, the loss of, and the fear of losing, autonomy and their independence and of being a burden on others were the most relevant. The identification of a cancer patient at risk of committing suicide forms the first step for the prevention of and the setting up of adequate psychosocial rehabilitation of these patients whenever possible.

Quality-of-life evaluation: when do terminal cancer patients and health-care providers agree?

A multicenter study involving six palliative care units in Italy was carried out on 159 terminal cancer patients seen at home or in hospital. The physician or the nurse completed independently from the patient the Therapy Impact Questionnaire (TIQ), a questionnaire devised for quality-of-life evaluation in terminal cancer patients. The patient's assessment was used as the valid reference measurement to compare with the health-care workers' evaluation to assess the validity of the latter. The results showed that percentages of agreement were higher for physical than for psychological and cognitive symptoms, and that there was a greater agreement on the absence rather than on the presence of a problem. None of the characteristics of the patient nor of the proxy showed any statistically significant relationship with the two disagreement indexes. The results suggest that caution is needed in the use of health-care workers as alternative sources of information regarding patients' quality of life.

Terminal cancer patients and timing of referral to palliative care: a multicenter prospective cohort study. Italian Cooperative Research Group on Palliative Medicine.

This study describes the characteristics of a representative sample of terminally ill cancer patients at admission to Italian palliative care programs, the rate and reasons for discontinuation of care, and survival after enrollment. All Italian palliative care units (PCUs) specifically committed to palliative care were asked to consecutively register all new patients (n = 3901) between January and June, 1995. Fifty-eight of the 62 PCUs contacted by the Steering Committee completed the study. A random sample of 589 evaluable patients was prospectively selected from the 2667 eligible patients. Patients were mostly referred by a general practitioner (31.2%) or a specialist (42.1%). Most patients (84.7%) were followed until death. Seventy-seven discontinued care because of hospital admission (6.6%), change of residence (3.9%), refusal (1.7%), or improvement (0.8%). Median survival was 37.9 days; 14.3% of the patients died within 7 days, and 15.3% lived longer than 180 days. A statistically significant association between survival and gender, cancer type, setting of the first visit, and type of unit was observed. In Italy, as in other countries with different health systems, referral of cancer patients to palliative care tends to occur late in the course of the disease. This study suggests that the process of enrollment and the duration of patients' survival in palliative care, when studied in large unselected populations, can provide important information relevant to the care of terminally ill patients.

Quality of life assessment and outcome of palliative care.

Quality of life (QoL) assessment is crucial for the evaluation of palliative care outcome. In this paper, our methodological approach was based on the creation of summary measures. Fifty-eight Palliative Care Units (PCUs) in Italy participated in the study. Each PCU randomly selected patients to be 'evaluated' among the consecutively 'registered' patients. At baseline (first visit) and each week the patient was asked to fill in a QoL questionnaire, the Therapy Impact Questionnaire (TIQ). Short-survivors (<7 days) were not included in the QoL study. The random sample of patients (n = 601) was highly representative of the general patient population cared for by the PCUs in Italy. The median survival was 37.9 days. We collected 3546 TIQ, 71.4 % completed by the patients. A Summary Measure Outcome score was calculated for 409 patients (81% of the patients included in the QoL study). The results of this national study showed that cooperative clinical research in palliative care is possible and QoL measures can be used to assess the outcome.

Psychosocial adaptation after liver transplantation with particular reference to recipients aware of their cancer.

This study investigated the Psychosocial adjustment in 40 patients who received orthotopic liver transplantation (OLT) for several endstage liver diseases. Twenty patients were grafted because they suffered from liver Cancer as well as cirrhosis. Particular attention was paid to evaluating whether cancer could affect recipients' coping with transplant. Each patient underwent a semi-structured interview to obtain information on their psychosocial life, relationship with the donor, organ acceptance and life expectancy. Interview was performed I year after transplantation. A psychodiagnostic evaluation was also performed using a Minnesota Multiphasic Personality Inventory (MMPI) and a Human Figure Test. Psychosocial adaptation in everyday life following liver transplantation seemed good in most of the patients, whatever the indication for transplantation might be. It can he seen that by replacing the diseased organ a high percentage of oncological patients overcame their fear of cancer.

Prevalence of sexual dysfunction in male cancer patients treated with rectal excision and coloanal anastomosis.

Impotency due to parasympathetic nerve injury is one of the most feared consequences of rectal cancer surgery. Sexual relationships make a significant contribution to the quality of life for almost everybody. Rectal excision and coloanal anastomosis (CAA) is a new surgical procedure for low rectal tumor with little data regarding the prevalence of sexual impairment as yet. We have examined the sexual life of 21 male patients who have undergone CAA by means a self-administered questionnaire. Only two patients reported reactive impotency. On the other hand 17 out of 21 patients had no ejaculation after undergoing surgery. According to our data it appears that CAA results in surgery a low degree of sexual impairment (impotency). Both sexual dysfunction and quality of life investigations should be integrated with oncological results when reporting data about colorectal surgery.