Outcomes of Patients Treated in the UK Proton Overseas Programme: Central Nervous System Group.

AIMS: In 2008, the UK National Health Service started the Proton Overseas Programme (POP), to provide access for proton beam therapy (PBT) abroad for selected tumour diagnoses while two national centres were being planned. The clinical outcomes for the patient group treated for central nervous system (CNS), base of skull, spinal and paraspinal malignancies are reported here. MATERIALS AND METHODS: Since the start of the POP, an agreement between the National Health Service and UK referring centres ensured outcomes data collection, including overall survival, local tumour control and late toxicity data. Clinical and treatment-related data were extracted from this national patient database. Grade ≥3 late toxicities were reported following Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 definition, occurring later than 90 days since the completion of treatment. RESULTS: Between 2008 and September 2020, 830 patients were treated within the POP for the above listed malignancies. Overall survival data were available for 815 patients and local control data for 726 patients. Toxicity analysis was carried out on 702 patients, with patients excluded due to short follow-up (<90 days) and/or inadequate toxicity data available. After a median follow-up of 3.34 years (0.06-11.58), the overall survival was 91.2%. The local control rate was 85.9% after a median follow-up of 2.81 years (range 0.04-11.58). The overall grade ≥3 late toxicity incidence was 11.97%, after a median follow-up of 1.72 years (0.04-8.45). The median radiotherapy prescription dose was 54 GyRBE (34.8-79.2). CONCLUSIONS: The results of this study indicate the safety of PBT for CNS tumours. Preliminary clinical outcomes following PBT for paediatric/teen and young adult and adult CNS tumours treated within the POP are encouraging, which reflects accurate patient selection and treatment quality. The rate of late effects compares favourably with published cohorts. Clinical outcomes from this patient cohort will be compared with those of UK-treated patients since the start of the national PBT service in 2018.

Bismuth nanowires with very low lattice thermal conductivity as revealed by the 3ω method.

Thermoelectric materials transform temperature gradients to voltages and vise versa. Despite their many advantages, devices based on thermoelectric materials are used today only in a few applications, due to their low efficiency, which is described by the figure of merit ZT. Theoretical studies predict that scaling down these materials to the nanometric scale should enhance their efficiency partially due to a decrease in their lattice thermal conductivity. In this work we determine for the first time the lattice thermal conductivity of 40 nm bismuth (Bi) nanowires (NWs), i.e. NWs with a diameter comparable to the Fermi wavelength of charge carriers in this material. We find a surprisingly low lattice thermal conductivity of 0.13 ± 0.05 W K(-1) m(-1) at 77 K. A quantitative argument, which takes into account several unique properties of Bi, is given to explain this unusual finding.

Body temperature as a risk factor for Alzheimer's disease.

A number of risk factors underlie the development of Alzheimer's disease. We propose low body temperature is also implicated. This is based on the belief that low temperature influences the biomechanics of the disease and promotes its development. Support for this hypothesis is found in a consideration of temperature effects on the disease process, in anecdotal observations and from our studies of people with Down syndrome.

Isolation and identification of nontuberculous mycobacteria from foods as possible exposure sources.

A variety of foods collected from local supermarkets and produce stands were examined as possible sources of nontuberculous mycobacterial exposure. Food samples were combined with sterile ultrapure water and manually shaken. To remove large particles, the suspensions were filtered through a sterile strainer, centrifuged, and the supernatants were discarded. The food pellets were stored at -75 degrees C. The pellets were treated with either oxalic acid or sodium hydroxide-sodium citrate solutions to reduce contamination by nonmycobacterial organisms. Decontaminated pellets were cultured on both Middlebrook 7H10C agar and Middlebrook 7H10C agar with supplemental malachite green. Plates were observed for growth at 2 and 8 weeks. Isolates demonstrating acid-fastness were identified to species using polymerase chain reaction and restriction enzyme analysis. Nontuberculous mycobacteria (NTM) were recovered from 25 of 121 foods. Six different species of NTM were isolated, the most predominant being Mycobacterium avium.

Managed behavioral health care: a Medicaid carve-out for youth.

This DataWatch assesses the impact of a public sector-managed Medicaid mental health carve-out pilot for North Carolina youth. Access to, volume of, and costs of mental health/substance abuse services are reported. We compared a pilot managed care program, with an incentive to shift hospital use and costs to community-based services, with usual fee-for-service Medicaid. Aggregate data from Medicaid claims for youth (from birth to age seventeen) statewide are reported for five years. We found dramatic reductions in use of inpatient care, with a shift to intensive outpatient services, and less growth in mental health costs. These findings demonstrate that public sector-managed care can be viable and more efficient than a fee-for-service model.

PCR comparison of Mycobacterium avium isolates obtained from patients and foods.

Mycobacterium avium is a cause of disseminated disease in AIDS patients. A need for a better understanding of possible sources and routes of transmission of this organism has arisen. This study utilized a PCR typing method designed to amplify DNA segments located between the insertion sequences IS1245 and IS1311 to compare levels of relatedness of M. avium isolates found in patients and foods. Twenty-five of 121 food samples yielded 29 mycobacterial isolates, of which 12 were M. avium. Twelve food and 103 clinical M. avium isolates were tested. A clinical isolate was found to be identical to a food isolate, and close relationships were found between two patient isolates and two food isolates. Relatedness between food isolates and patient isolates suggests the possibility that food is a potential source of M. avium infection. This study demonstrates a rapid, inexpensive method for typing M. avium, possibly replacing pulsed-field gel electrophoresis.

Comparison of large restriction fragments of Mycobacterium avium isolates recovered from AIDS and non-AIDS patients with those of isolates from potable water.

We examined potable water in Los Angeles, California, as a possible source of infection in AIDS and non-AIDS patients. Nontuberculous mycobacteria were recovered from 12 (92%) of 13 reservoirs, 45 (82%) of 55 homes, 31 (100%) of 31 commercial buildings, and 15 (100%) of 15 hospitals. Large-restriction-fragment (LRF) pattern analyses were done with AseI. The LRF patterns of Mycobacterium avium isolates recovered from potable water in three homes, two commercial buildings, one reservoir, and eight hospitals had varying degrees of relatedness to 19 clinical isolates recovered from 17 patients. The high number of M. avium isolates recovered from hospital water and their close relationship with clinical isolates suggests the potential threat of nosocomial spread. This study supports the possibility that potable water is a source for the acquisition of M. avium infections.

Molecular technique for rapid identification of mycobacteria.

Identification of mycobacteria through conventional microbiological methods is cumbersome and time-consuming. Recently we have developed a novel bacterial identification method to accurately and rapidly identify different mycobacteria directly from water and clinical isolates. The method utilizes the PCR to amplify a portion of the small subunit rRNA from mycobacteria. The 5' PCR primer has a fluorescent label to allow detection of the amplified product. The PCR product is digested with restriction endonucleases, and an automated DNA sequencer is employed to determine the size of the labeled restriction fragments. Since the PCR product is labeled only at the 5' end, the analysis identifies only the restriction fragment proximal to the 5' end. Each mycobacterial species has a unique 5' restriction fragment length for each specific endonuclease. However, frequently the 5' restriction fragments from different species have similar or identical lengths for a given endonuclease. A set of judiciously chosen restriction enzymes produces a unique set of fragments for each species, providing us with an identification signature. Using this method, we produced a library of 5' restriction fragment sizes corresponding to different clinically important mycobacteria. We have characterized mycobacterial isolates which had been previously identified by biochemical test and/or nucleic acid probes. An analysis of these data demonstrates that this protocol is effective in identifying 13 different mycobacterial species accurately. This protocol has the potential of rapidly (less than 36 h) identifying mycobacterial species directly from clinical specimens. In addition, this protocol is accurate, sensitive, and capable of identifying multiple organisms in a single sample.

Pertussis immunization and characteristics related to first seizures in infants and children.

In a previous study in which we examined the relationship of pertussis immunization to the onset of neurologic disorders during 1967 and 1968 and during 1972 and 1973 in Denmark, there were 554 children with initial onset of epilepsy and 2158 children with first febrile convulsions. In the study population there were 112 children with epilepsy and 229 children with febrile convulsions for whom the exact date of pertussis immunization and the exact date of the onset of illness were known. We analyzed selected clinical variables by specific time intervals between pertussis immunization and the first seizure. In the children with epilepsy, no relationship was found between time of pertussis immunization and the specific variables that were examined. In contrast, the following characteristics in children with febrile seizures were significantly more common when pertussis immunization had occurred within 3 days, compared with more than 7 days of the event: first seizure more than 10 minutes in duration, the occurrence of more than one seizure, the longest seizure (when there was more than one) more than 10 minutes in duration, and the occurrence of a seizure described as focal. The lack of specific characteristics in epilepsy that had its onset in a temporal relationship to pertussis immunization is further evidence that pertussis vaccine does not cause this disorder. The cause of increased severity of febrile seizures apparently associated with pertussis immunization is unknown.

An ongoing surveillance study of persistent crying and hypotonic-hyporesponsive episodes following routine DTP immunization: a preliminary report.

Hypotonic-hyporesponsive episodes and persistent crying are specific complications of pertussis immunization. Hyperinsulinemia, hypoglycemia, and leukocytosis have been noted after pertussis vaccine administration in a murine model. Five children with hypotonic-hyporesponsive episodes and 6 children with persistent crying following DTP immunization were studied. The children were found to have leukocytosis acutely, similar to findings reported in children following routine DTP immunization. No abnormalities were noted in plasma insulin or serum glucose. Five of 6 children with persistent crying had severe local reactions, suggesting that localized inflammation may be a cause of persistent crying.

Typical, modified, and atypical measles.

A small outbreak of measles that occurred in August and September of 1975 was studied. One adolescent boy who had received killed measles vaccine 12 years previously had atypical measles, a 31-year-old woman had typical primary measles, and two other boys with measles were live vaccine failures. Of these latter two cases, clinical and serologic findings suggest that one boy had primary vaccine failure and the other may have had a secondary immunologic response. The findings of this study, as well as the results of other recent investigations, suggest that measles will be of increasing concern for the internist.