Assertive outreach treatment versus care as usual for the treatment of high-need, high-cost alcohol related frequent attenders: study protocol for a randomised controlled trial.

BACKGROUND: Alcohol-related hospital admissions have doubled in the last ten years to > 1.2 m per year in England. High-need, high-cost (HNHC) alcohol-related frequent attenders (ARFA) are a relatively small subgroup of patients, having multiple admissions or attendances from alcohol during a short time period. This trial aims to test the effectiveness of an assertive outreach treatment (AOT) approach in improving clinical outcomes for ARFA, and reducing resource use in the acute setting. METHODS: One hundred and sixty ARFA patients will be recruited and following baseline assessment, randomly assigned to AOT plus care as usual (CAU) or CAU alone in equal numbers. Baseline assessment includes alcohol consumption and related problems, physical and mental health comorbidity and health and social care service use in the previous 6 months using standard validated tools, plus a measure of resource use. Follow-up assessments at 6 and 12 months after randomization includes the same tools as baseline plus standard measure of patient satisfaction. Outcomes for CAU + AOT and CAU at 6 and 12 months will be compared, controlling for pre-specified baseline measures. Primary outcome will be percentage of days abstinent at 12 months. Secondary outcomes include emergency department (ED) attendance, number and length of hospital admissions, alcohol consumption, alcohol-related problems, other health service use, mental and physical comorbidity 6 and 12 months post intervention. Health economic analysis will estimate the economic impact of AOT from health, social care and societal perspectives and explore cost-effectiveness in terms of quality adjusted life years and alcohol consumption at 12-month follow-up. DISCUSSION: AOT models piloted with alcohol dependent patients have demonstrated significant reductions in alcohol consumption and use of unplanned National Health Service (NHS) care, with increased engagement with alcohol treatment services, compared with patients receiving CAU. While AOT interventions are costlier per case than current standard care in the UK, the rationale for targeting HNHC ARFAs is because of their disproportionate contribution to overall alcohol burden on the NHS. No previous studies have evaluated the clinical and cost-effectiveness of AOT for HNHC ARFAs: this randomized controlled trial (RCT) targeting ARFAs across five South London NHS Trusts is the first. TRIAL REGISTRATION: International standard randomized controlled trial number (ISRCTN) registry: ISRCTN67000214, retrospectively registered 26/11/2016.

Maximum proton kinetic energy and patient-generated neutron fluence considerations in proton beam arc delivery radiation therapy.

Several compact proton accelerator systems for use in proton therapy have recently been proposed. Of paramount importance to the development of such an accelerator system is the maximum kinetic energy of protons, immediately prior to entry into the patient, that must be reached by the treatment system. The commonly used value for the maximum kinetic energy required for a medical proton accelerator is 250 MeV, but it has not been demonstrated that this energy is indeed necessary to treat all or most patients eligible for proton therapy. This article quantifies the maximum kinetic energy of protons, immediately prior to entry into the patient, necessary to treat a given percentage of patients with rotational proton therapy, and examines the impact of this energy threshold on the cost and feasibility of a compact, gantry-mounted proton accelerator treatment system. One hundred randomized treatment plans from patients treated with IMRT were analyzed. The maximum radiological pathlength from the surface of the patient to the distal edge of the treatment volume was obtained for 180 degrees continuous arc proton therapy and for 180 degrees split arc proton therapy (two 90 degrees arcs) using CT# profiles from the Pinnacle (Philips Medical Systems, Madison, WI) treatment planning system. In each case, the maximum kinetic energy of protons, immediately prior to entry into the patient, that would be necessary to treat the patient was calculated using proton range tables for various media. In addition, Monte Carlo simulations were performed to quantify neutron production in a water phantom representing a patient as a function of the maximum proton kinetic energy achievable by a proton treatment system. Protons with a kinetic energy of 240 MeV, immediately prior to entry into the patient, were needed to treat 100% of patients in this study. However, it was shown that 90% of patients could be treated at 198 MeV, and 95% of patients could be treated at 207 MeV. Decreasing the proton kinetic energy from 250 to 200 MeV decreases the total neutron energy fluence produced by stopping a monoenergetic pencil beam in a water phantom by a factor of 2.3. It is possible to significantly lower the requirements on the maximum kinetic energy of a compact proton accelerator if the ability to treat a small percentage of patients with rotational therapy is sacrificed. This decrease in maximum kinetic energy, along with the corresponding decrease in neutron production, could lower the cost and ease the engineering constraints on a compact proton accelerator treatment facility.

Contribution to Neutron Fluence and Neutron Absorbed Dose from Double Scattering Proton Therapy System Components.

Proton therapy offers low integral dose and good tumor comformality in many deep-seated tumors. However, secondary particles generated during proton therapy, such as neutrons, are a concern, especially for passive scattering systems. In this type of system, the proton beam interacts with several components of the treatment nozzle that lie along the delivery path and can produce secondary neutrons. Neutron production along the beam's central axis in a double scattering passive system was examined using Monte Carlo simulations. Neutron fluence and energy distribution were determined downstream of the nozzle's major components at different radial distances from the central axis. In addition, the neutron absorbed dose per primary proton around the nozzle was investigated. Neutron fluence was highest immediately downstream of the range modulator wheel (RMW) but decreased as distance from the RMW increased. The nozzle's final collimator and snout also contributed to the production of high-energy neutrons. In fact, for the smallest treatment volume simulated, the neutron absorbed dose per proton at isocenter increased by a factor of 20 due to the snout presence when compared with a nozzle without a snout. The presented results can be used to design more effective local shielding components inside the treatment nozzle as well as to better understand the treatment room shielding requirements.

Improving screening and brief intervention activities in primary health care: Secondary analysis of professional accuracy based on the AUDIT-C.

INTRODUCTION AND OBJECTIVE: The ODHIN trial found that training and support and financial reimbursement increased the proportion of patients that were screened and given advice for their heavy drinking in primary health care. However, the impact of these strategies on professional accuracy in delivering screening and brief advice is underresearched and is the focus of this paper. METHOD: From 120 primary health care units (24 in each jurisdiction: Catalonia, England, the Netherlands, Poland, and Sweden), 746 providers participated in the baseline and the 12-week implementation periods. Accuracy was measured in 2 ways: correctness in completing and scoring the screening instrument, AUDIT-C; the proportion of screen-negative patients given advice, and the proportion of screen-positive patients not given advice. Odds ratios of accuracy were calculated for type of profession and for intervention group: training and support, financial reimbursement, and internet-based counselling. RESULTS: Thirty-two of 36 711 questionnaires were incorrectly completed, and 65 of 29 641 screen-negative patients were falsely classified. At baseline, 27% of screen-negative patients were given advice, and 22.5% screen-positive patients were not given advice. These proportions halved during the 12-week implementation period, unaffected by training. Financial reimbursement reduced the proportion of screen-positive patients not given advice (OR = 0.56; 95% CI, 0.31-0.99; P < .05). CONCLUSION: Although the use of AUDIT-C as a screening tool was accurate, a considerable proportion of risky drinkers did not receive advice, which was reduced with financial incentives.

Codeine use, dependence and help-seeking behaviour in the UK and Ireland: an online cross-sectional survey.

BACKGROUND: Codeine misuse and dependence poses a clinical and public health challenge. However, little is known about dependence and treatment needs in the UK and Ireland. AIM: To characterize codeine use, dependence and help-seeking behaviour. DESIGN: An online cross-sectional survey advertised on Facebook, Twitter, health and drug websites and e-mail circulars. METHODS: The survey collected data on demographics and codeine use amongst adults from the UK and Ireland. The Severity of Dependence Scale measured the level of codeine dependence. RESULTS: The sample of 316 respondents had a mean age of 35.3 years (SD = 12.3) and 67% were women. Of the 316 respondents, 54 scored ≥5 on the Severity of Dependence Scale indicating codeine dependence (17.1%). Our study found that codeine dependence is a problem with both prescribed and 'over-the-counter' codeine. Codeine dependence was associated with daily use of codeine, faking or exaggerating symptoms to get a prescription for codeine and 'pharmacy shopping' ( P < 0.01). A higher number of respondents had sought advice on the Internet (12%) rather than from their general medical practitioner (GP) (5.4%). Less than 1% of respondents had sought advice from a pharmacist. CONCLUSIONS: Codeine dependent users were more likely to seek help on the Internet to control their use of codeine than from a GP, which may indicate a potential for greater specialized addiction treatment demand through increased identification and referrals in primary care.

[Salvia divinorum--representation of a new drug in the Internet]. / Salvia divinorum--Präsenz einer neuen Droge im Internet.

AIM OF THE STUDY: The German pages of the Internet were searched for the presence of the hallucinogenic herbal drug Salvia divinorum, which is not dealt with in current addiction medicine or psychiatric text books. The investigation is part of the EU sponsored project "Psychonaut" as preparatory work for the development of an Internet-based early warning system. METHODS: The first 100 websites of the search using "Salvia divinorum" were compared with the search results for "cannabis" and "LSD". The following aspects of the sites were especially analyzed: the originator, marketing of drugs, and the attitude towards drug use. RESULTS: Salvia was offered for sale on approximately a third of the sites (29%); cannabis and LSD were not marketed on any sites. Official websites such as those from governmental organizations or universities were seldom found when searching for "Salvia divinorum", and then only under the last hits. The percentage of institutional sites (e. g. public organizations) were 12% with Salvia, 21% with cannabis, and 38% with LSD. A drug-friendly attitude was found at 64 % of the sites with regard to Salvia, 58% for cannabis, and 24% for LSD. CONCLUSION: The drug help system must be aware of that the Internet is a source of drug-related information, and of drug trade. As this investigation shows, sites often have a drug-friendly attitude. The low availability of official information on Salvia divinorum (also outside the Internet) relative to the presence of drug-friendly or drug trading sites is an indication that new trends of drug consumption can be tracked in the Internet before they will be found in official literature.

The RBE issues in ion-beam therapy: conclusions of a joint IAEA/ICRU working group regarding quantities and units.

This paper summarises the conclusions of a working group established jointly by the International Atomic Energy Agency (IAEA) and the International Commission on Radiation Units and Measurements (ICRU) to address some of the relative biological effectiveness (RBE) issues encountered in ion-beam therapy. Special emphasis is put on the selection and definition of the involved quantities and units. The isoeffective dose, as introduced here for radiation therapy applications, is the dose that delivered under reference conditions would produce the same clinical effects as the actual treatment in a given system, all other conditions being identical. It is expressed in Gy. The reference treatment conditions are: photon irradiation, 2 Gy per fraction, 5 daily fractions a week. The isoeffective dose D(IsoE) is the product of the physical quantity absorbed dose D and a weighting factor W(IsoE). W(IsoE) is an inclusive weighting factor that takes into account all factors that could influence the clinical effects like dose per fraction, overall time, radiation quality (RQ), biological system and effects. The numerical value of W(IsoE) is selected by the radiation-oncology team for a given patient (or treatment protocol). It is part of the treatment prescription. Evaluation of the influence of RQ on W(IsoE) raises complex problems because of the clinically significant RBE variations with biological effect (late vs. early) and position in depth in the tissues which is a problem specific to ion-beam therapy. Comparison of the isoeffective dose with the equivalent dose frequently used in proton- and ion-beam therapy is discussed.

Novel psychoactive substances: An investigation of temporal trends in social media and electronic health records.

BACKGROUND: Public health monitoring is commonly undertaken in social media but has never been combined with data analysis from electronic health records. This study aimed to investigate the relationship between the emergence of novel psychoactive substances (NPS) in social media and their appearance in a large mental health database. METHODS: Insufficient numbers of mentions of other NPS in case records meant that the study focused on mephedrone. Data were extracted on the number of mephedrone (i) references in the clinical record at the South London and Maudsley NHS Trust, London, UK, (ii) mentions in Twitter, (iii) related searches in Google and (iv) visits in Wikipedia. The characteristics of current mephedrone users in the clinical record were also established. RESULTS: Increased activity related to mephedrone searches in Google and visits in Wikipedia preceded a peak in mephedrone-related references in the clinical record followed by a spike in the other 3 data sources in early 2010, when mephedrone was assigned a 'class B' status. Features of current mephedrone users widely matched those from community studies. CONCLUSIONS: Combined analysis of information from social media and data from mental health records may assist public health and clinical surveillance for certain substance-related events of interest. There exists potential for early warning systems for health-care practitioners.

Lung calcium-dependent phospholipid-binding proteins: structure and function.

Distinct peptide maps of two rabbit lung Ca2(+)-dependent phospholipid-binding proteins (PLBPs), 36,000 and 33,000, were generated by cyanogen bromide (CNBr) cleavage, trypsin or Staphylococcus aureus V8 proteinase digestion. The amino acid sequence of a CNBr-cleaved peptide of the 36,000 PLBP was aligned to the amino terminus of human lipocortin I with more than 77% identity, but had no identity with the known amino terminal sequence of other known annexins. Partial amino acid sequence of a 33,000 PLBP peptide demonstrated a close (56%) relationship to endonexin II, human placental anticoagulant protein, and porcine intestine protein II, but shared only 32% identity with lipocortin I, 30% with lipocortin II. Antiserum generated against purified 36,000 PLBP reacted strongly with the 33,000 PLBP, but did not react with any other rabbit lung cytosolic proteins. Both PLBPs inhibited the phospholipase A2 reaction when dioleoyl phosphatidylcholine and phosphatidylglycerol vesicles or monolayers were used as substrates. In the vesicle assay, the phospholipase A2 reaction was inhibited at lower substrate phospholipid concentrations but not at nearly saturating substrate concentrations. In the monolayer assay, the phospholipid-binding proteins did not inhibit phospholipase A2 at a low phospholipid surface concentration of 3.8.10(-3) molecules/A2, but they did at higher surface concentrations between 1.1 x 10(-2) and 3.8 x 10(-2) molecules/A2. The inhibition of phospholipase A2 by rabbit lung phospholipid-binding proteins is most likely due to the prevention of penetration by phospholipase A2 into the interface, a requirement for the enzyme to act on the substrate.

Oral administration of unsaturated fatty acids: effects on human peripheral blood T lymphocyte proliferation.

Oils enriched in certain polyunsaturated fatty acids suppress joint pain and swelling in rheumatoid arthritis (RA) patients. Because T lymphocyte activation is important to propagation of joint tissue injury in patients with RA, we examined the effects of fatty acids administered by mouth in vivo on proliferation of human lymphocytes activated through the T cell receptor complex. T cell proliferation was reduced after oral administration of 2.4 g gammalinolenic acid in capsules of borage seed oil. Oral administration of oils enriched in linoleic acid, the parent n-6 fatty acid, and alpha linolenic acid, the parent n-3 fatty acid, did not influence growth of stimulated cells. Fatty acid analyses indicated that suppression of lymphocyte proliferation after gammalinolenic acid administration was associated with increased plasma and peripheral blood mononuclear cell concentrations of gammalinolenic acid and dihomogammalinolenic acid.

Skeletal effects of calcitonin in ovariectomized rats.

Although calcitonin (CT) has been shown to be effective for the prevention of bone loss in early postmenopausal women, the skeletal effects of the hormone specifically during the early stages of estrogen deficiency have not been characterized histomorphometrically to date. The current study involves use of the ovariectomized (OVX) rat as an animal model for early postmenopausal bone loss to perform such a histomorphometric analysis. One group of OVX rats was injected sc with salmon CT on alternate days for a 6-week period. Additional groups of OVX and sham-operated control rats were treated with vehicle alone. In comparison to control rats, the proximal tibia of vehicle-treated OVX rats were characterized by a 3-fold decrease in cancellous bone volume and significant increases in osteoblast surface (+200%), osteoclast surface (+143%), mineralizing surface (+111%), mineral apposition rate (+36%), bone formation rate (+181%), and longitudinal bone growth (+38%). In contrast, treatment of OVX rats with CT normalized tibial cancellous bone volume and significantly decreased all of the above cellular- and fluorochrome-based indices of bone turnover to near control levels. The results indicate that CT treatment depresses bone turnover and prevents the development of osteopenia in OVX rats. These findings are consistent with the bone protective effect of CT in early postmenopausal women and further support the OVX rat as an animal model for the preclinical evaluation of prophylactic treatments for postmenopausal bone loss.

A comparison of the skeletal effects of intermittent and continuous administration of calcitonin in ovariectomized rats.

The study was designed to compare the skeletal effects of intermittent and continuous administration of calcitonin (CT) in ovariectomized (OVX) rats. Female rats were sham operated or OVX at 3 months of age and treated for 6 weeks with vehicle or salmon CT. Sham-operated control rats were injected subcutaneously with vehicle on alternate days. One group of OVX rats was treated with vehicle intermittently by subcutaneous injection or continuously via Alzet osmotic minipumps. The remaining OVX rats were treated with CT by either subcutaneous injections (16 U/kg) on alternate days or by continuous infusion via minipumps at a daily dose of 8 U/kg. OVX rats treated with CT continuously were mildly hypocalcemic compared with all other groups. The proximal tibial metaphyses of vehicle-treated OVX rats were osteopenic with a cancellous bone volume at only 28% of the vehicle-treated control level. This bone loss was associated with increased indices of bone turnover such as osteoclast surface, osteoblast surface, and bone formation rate. Cancellous bone volume in OVX rats treated with CT either intermittently or continuously was significantly higher than that of vehicle-treated OVX rats, but lower than that of vehicle-treated control rats. Treatment of OVX rats with intermittent or continuous CT significantly decreased all indices of bone turnover compared with vehicle-treated OVX rats. However, osteoclast and osteoblast surfaces of OVX rats treated with CT continuously were still significantly higher than those of vehicle-treated control rats. These results indicate that intermittent and continuous administration of CT had similar skeletal effects in OVX rats. Both treatment regimens depressed bone turnover and partially prevented cancellous bone loss in the estrogen-deplete skeleton.

Survival of parenchymal hepatocytes irradiated with 14.3 MeV neutrons.

The purpose of these experiments was to estimate the RBE of neutrons for parenchymal hepatocytes as a function of neutron dose and to determine the ability of liver cells to repair potentially lethal damage (PLD) after neutron exposure. Hepatocyte reproductive survival was used as the biological end point in these studies and hepatocyte survival was determined with an in vivo transplantation clonogenic assay system. The 14.3 MeV neutrons were generated by a D-T reaction at the University of Wisconsin's gas target neutron source. The average neutron dose rate was 20 cGy/min. The estimated survival data for neutron exposed hepatocytes were best described by a single hit-single target model (i.e., n = 1.0) with a D0 = 170 cGy. In contrast to the results obtained with 60Co, hepatocytes exposed to neutrons are unable to repair PLD. The RBE value, when the reproductive survival was estimated 30 min after radiation exposure, is independent of neutron dose and equal to 1.6 +/- 0.1. In contrast, when the reproductive survival was estimated 24 hrs after radiation exposure, the RBE was found to increase with decreasing neutron dose and equal 4.2 +/- 0.5 at 50 cGy.

Co-mutagenic effects of 2-aminoanthracene and cigarette smoke condensate on smoker's urine in the Ames Salmonella assay system.

Cigarette smoke condensate (CSC) and cigarette smoker's urine (concentrated) (UC) were tested alone and in combination with direct and indirect mutagens for histidine reversion in the Ames Salmonella assay system. While both CSC and smoker's urine showed some mutagenic activity upon metabolic activation with S9-mix, each of them in combination with the aromatic amine 2-aminoanthracene (2AA) exhibited a synergistic effect on mutagenicity. Such a synergistic effect was not found when these agents were combined with the direct mutagens, ethylmethane sulfonate (EMS) and methylmethane sulfonate (MMS), or the indirect mutagens, benzo[a]pyrene (BP) and 9,10-dimethyl-1,2-benzanthracene (DMBA), tested in this study, nor was the synergistic effect observed when 2AA was tested with urine from a non-smoker. The results, thus, reflected a specificity of the co-mutagenic action of factor(s) in cigarette smoke or smoker's urine and 2AA. The significance of co-mutagens in carcinogenesis has been discussed and the importance of investigating co-mutagenesis particularly in the case of suspected human exposure to multiple environmental agents has been emphasized.

Mapping health in the Great Lakes areas of concern: a user-friendly tool for policy and decision makers.

The role of the physical environment as a determinant of health is a major concern reported by the general public as well as by many policymakers. However, it remains one of the health determinants for which few available measures or indicators are readily available. This lack of data is compounded by the fact that evidence for direct cause-and-effect relationships in the literature is often equivocal, leading to feelings of uncertainty among the lay public and often leading to indecision among policymakers. In this article we examine one aspect of the physical environment--water pollution in the Great Lakes Areas of Concern (AOCs)--and its potential impacts on a wide range of (plausible) human health outcomes. Essentially, the International Joint Commission, the international agency that oversees Great Lakes water quality and related issues, worked with Health Canada to produce a report for each of the 17 AOCs on the Canadian side of the Great Lakes, outlining a long list of health outcomes and the potential relationships these might have with environmental exposures known or suspected to exist in the Great Lakes basin. These reports are based solely on secondary health data and a thorough review of the environmental epidemiologic literature. The use of these reports by local health policymakers as well as by public health officials in the AOCs was limited, however, by the presentation of vast amounts of data in a series of tables with various outcome measures. The reports were therefore not used widely by the audience for whom they were intended. In this paper we report the results of an undertaking designed to reduce the data and present them in a more policy-friendly manner, using a geographic information system. We do not attempt to answer directly questions related to cause and effect vis-à-vis the relationships between environment and health in the Great Lakes; rather, this work is a hypothesis-generating exercise that will help sharpen the focus of research into this increasingly important area of public health concern.

Botanical lipids: effects on inflammation, immune responses, and rheumatoid arthritis.

OBJECTIVE: This review discusses the rationale and experimental data that led to clinical trials of certain botanical lipids, mainly gammalinolenic acid (GLA), for the treatment of rheumatoid arthritis (RA). DATA SOURCES: Pertinent articles and reviews, and a bibliographic database in English using the following indexing terms: rheumatoid arthritis, fatty acids, gammalinolenic acid, lymphocytes, and monocytes, were used. STUDY SELECTION: All clinical trials in which GLA was used to treat arthritis are included in this review. Data from appropriately peer reviewed in vitro and animal experiments evaluating the effects of botanical lipids as regulators of cell activation and immune responses are also reviewed. DATA SYNTHESIS: GLA treatment is associated with clinical improvement in patients with RA, as evaluated by duration of morning stiffness, joint pain and swelling, and ability to reduce other medications. However, studies vary in terms of duration, GLA dose, whether or not they were placebo controlled, and, if so, what placebo was used, criteria for evaluation, and use of concomitant medication. Studies done in vitro generally indicated that GLA reduces lymphocyte activation and production of mediators of inflammation. CONCLUSIONS: A small number of studies suggest that GLA is effective treatment for RA patients. Further controlled studies of its use in RA seem warranted.

Negative and positive transcriptional control during cell proliferation (Review).

A significant amount of experimental evidence has demonstrated that progression of the cell cycle in mammalian cells is associated with periodic transcriptional activation/ repression of growth-regulatory genes. We summarize our current knowledge and views on the role of the critical cell cycle regulators such as the retinoblastoma proteins in transcription repression and their functional connections with various different transcription factors. In addition, we discuss the role of oncogenes such as TIF1 alpha, PML and RFL which belong to a characteristic subgroup of RING finger proteins that contain the RING finger (C3HC4 zinc finger) the B-boxes and a putative coiled-coil (RBCC configuration) as mediators of transcription repression.

Return to fertility after extended chemical castration with a GnRH antagonist.

BACKGROUND: Antagonistic analogues of GnRH for the treatment of prostate cancer may be used clinically in persons for whom return to fertility after such treatment is important or desirable. The purpose of this study was, therefore, to evaluate the effects of a long term treatment with orntide, a GnRH antagonist, on testosterone levels and fertility in male rats. METHODS: Two groups of male rats received either 120-day orntide microspheres (8.8 mg orntide/kg/120 days) or vehicle alone (control group). Serum orntide and testosterone levels in both groups were monitored at certain intervals for 9 months from the initiation of treatment. After recovery of normal serum testosterone levels in the treated animals, each rat was housed with two proven breeder, but drug-naive, females. RESULTS: All mates of treated rats achieved pregnancy as rapidly as the mates of control rats although two of the control rats did not sire a litter with either female and one sired only one litter. The mean size of the litters of treated (12.3 offspring per litter) and control (10.6 offspring per litter) were similar. All offspring were grossly normal morphologically and behaviorally during the time to weaning. CONCLUSIONS: These results suggest that lack of fertility due to testosterone suppression is reversible after cessation of treatment with this GnRH antagonist.

Effect of pulsed dose in simultaneous and sequential irradiation of V-79 cells by 14.8-MeV neutrons and 60Co photons.

The effect of irradiating V-79 Chinese hamster cells with a mixture of 40% 14.8-MeV neutrons and 60% 60Co photons with simultaneous or sequential exposures is investigated. Sample doses are obtained by irradiating cells with alternating 3-min pulses of neutrons and photons (in the sequential case) or with mixed neutrons and photons followed by equal beam-off periods to ensure equal total exposure times for sequential and simultaneous irradiations. Differences between the survival results under each beam configuration that are consistent with previous observations with nonpulsed irradiations are observed.