An optimal algorithm for configuring delivery options of a one-dimensional intensity-modulated beam

The problem of generating delivery options for one-dimensional intensity-modulated beams (1D IMBs) arises in intensity-modulated radiation therapy. In this paper, we present an algorithm with the optimal running time, based on the 'rightmost-preference' method, for generating all distinct delivery options for an arbitrary 1D IMB. The previously best known method for generating delivery options for a 1D IMB with N left leaf positions and N right leaf positions is a 'brute-force' solution, which first generates all N! possible combinations of the left and right leaf positions and then removes combinations that are not physically allowed delivery options. Compared with the brute-force method, our algorithm has several advantages: (1) our algorithm runs in an optimal time that is linearly proportional to the total number of distinct delivery options that it actually produces. Note that for a 1D IMB with multiple peaks, the total number of distinct delivery options in general tends to be considerably smaller than the worst case N!. (2) Our algorithm can be adapted to generating delivery options subject to additional constraints such as the 'minimum leaf separation' constraint. (3) Our algorithm can also be used to generate random subsets of delivery options; this feature is especially useful when the 1D IMBs in question have too many delivery options for a computer to store and process. The key idea of our method is that we impose an order on how left leaf positions should be paired with right leaf positions. Experiments indicated that our rightmost-preference algorithm runs dramatically faster than the brute-force algorithm. This implies that our algorithm can handle 1D IMBs whose sizes are substantially larger than those handled by the brute-force method. Applications of our algorithm in therapeutic techniques such as intensity-modulated arc therapy and 2D modulations are also discussed.     

Serial adoptive transfer of murine experimental allergic encephalomyelitis: successful transfer is dependent on active disease in the donor

In an attempt to understand the mechanisms underlying disease progression in adoptively transferred experimental allergic encephalomyelitis (EAE), and perhaps multiple sclerosis (MS), this study has examined the transfer of EAE serially from primary to secondary and tertiary recipients using myelin basic protein (MBP)-responsive lymphocytes. It was found that EAE could be serially transferred only when there was acute or relapsing disease activity in the donor animal. Cells from donors with quiescent disease did not transfer EAE. Autoradiographic attempts to locate primary adoptively transferred cells in the central nervous system of secondary and tertiary recipients were uniformly unsuccessful. These findings implicate the requirement of effector cell activation in the donor and the recruitment of augmenting autoimmune cells in lesion formation.     

Estimating the burden and cost of infectious intestinal disease in the Maltese community

The aim of this study was to estimate the burden of infectious intestinal disease (IID) and cost of illness at the community level from a societal aspect. A retrospective, age-stratified cross-sectional telephone study was carried out in Malta in 2004-2005. The number of cases, resources used and cost of resources were computed. The resources involved direct costs (health-care services, stool culture tests, medicines and personal costs) and indirect costs (costs from lost employment by cases and caregivers). This study estimated 0.421 (95% CI 0.092-0.771) separate episodes of IID per person per year in Malta which corresponds to 164 471 (95% CI 35 941-301 205) episodes of IID per year or 450 (95% CI 98-825) episodes of IID each day. The largest proportion of cost is due to provision of health-care services with euro10 454 901 [Maltese liri (Lm) 4 558 970] per year; followed by euro963 295 (Lm 2 209 393) in lost productivity; euro1 286 286 (Lm 561 078) in medicines; euro152 335 (Lm 66 452) in stool culture testing and euro71 487 (Lm 31 183) in personal costs, giving a total cost of illness of over euro16 million (7 million Lm) per year. The burden and cost of IID are high enough to justify efforts to control the illness. Such estimates are important to assess the cost-effectiveness of proposed specific interventions.     

Is ultraviolet B irradiance inversely associated with incidence rates of endometrial cancer: an ecological study of 107 countries

OBJECTIVE: The purpose of this study was to perform an ecological analysis of the relationship between low levels of ultraviolet B (UVB) irradiance and age-standardized incidence rates of endometrial cancer by country, controlling for known confounders. METHODS: The contributions of UVB irradiance, cloud cover, intake of energy from animal sources, proportion of population overweight, skin pigmentation, per capita cigarette consumption, per capita health expenditure, and total fertility rates, to age-standardized incidence rates of endometrial cancer in 107 countries were assessed using multiple regression. RESULTS: Incidence rates were higher at higher latitudes (R2=0.47, p<0.01). According to multiple regression, UVB irradiance adjusted for cloud cover was negatively associated with incidence rates (p=0.02), while proportion of population overweight (p=0.004), intake of energy from animal sources (p=0.01) and per capita health expenditure (p<0.0001) were positively associated with incidence rates (overall R2=0.73, p<0.0001). CONCLUSION: An association was found between low UVB irradiance, high intake of energy from animal sources, per capita health expenditure, proportion of population overweight, and incidence rates.     

Combination of quinupristin-dalfopristin and gentamicin against methicillin-resistant Staphylococcus aureus: experimental rabbit endocarditis study

The combination of quinupristin-dalfopristin (Q-D) and gentamicin was tested against two strains of gentamicin- and dalfopristin-susceptible methicillin-resistant Staphylococcus aureus (MRSA). One strain was susceptible to macrolides, lincosamides, and streptogramin B type antibiotics (MLS(B)), and the other was constitutively resistant to these antibiotics by virtue of the ermA gene. The checkerboard method and time-kill curves showed that the combination of Q-D and gentamicin was indifferent. A rabbit endocarditis model simulated the pharmacokinetics achieved in humans receiving intravenous injections of Q-D (7.5 mg/kg of body weight three times a day) and gentamicin (3 mg/kg once daily). For the MLS(B)-susceptible strain, a 4-day regimen reduced mean bacterial titers (MBT) in vegetations from 8.5 +/- 0.8 log CFU/g (control group) to 4.1 +/- 2.6 (gentamicin), 3.0 +/- 0.9 (Q-D), and 2.6 +/- 0.5 log CFU/g (Q-D plus gentamicin). For the strain constitutively resistant to MLS(B), a 4-day regimen reduced MBT in vegetations from 8.7 +/- 0.9 log CFU/g (control group) to 5.0 +/- 2.2 (gentamicin), 5.2 +/- 2.2 (Q-D), and 5.1 +/- 2.4 log CFU/g (Q-D plus gentamicin). The differences between control and treatment groups were significant for both strains (P < 0.0001), although there was no significant difference between treatment groups. No resistant variant was isolated from vegetations, and no significant difference in MBT in vegetations of treatment groups after 1-day regimens was observed. This experimental study found no additive benefit in combining Q-D and gentamicin against dalfopristin- and gentamicin-susceptible MRSA.     

A neutralizing monoclonal antibody (mAb A24) directed against the transferrin receptor induces apoptosis of tumor T lymphocytes from ATL patients

Adult T-cell leukemia/lymphoma (ATL) is an aggressive lymphoid proliferative disease that exists under diverse clinical forms ranging from chronic to acute. Although leukemic cells from patients with ATL exhibit an intrinsic resistance to chemotherapy, monoclonal antibodies directed against CD25 (interleukin 2 receptor alpha [IL-2Ralpha] antibody) have been used as specific therapeutic agents. However, significant clinical results with these antibodies have been demonstrated only in chronic forms of ATL. In contrast to resting T cells, human T-cell lymphotropic virus type 1 (HTLV-1)-infected cells constitutively express high levels of surface transferrin receptor (TfR). Herein, we report the characterization of a new monoclonal antibody (mAb A24) directed against the human TfR and the evaluation of its capacity to block the proliferation of ATL cells ex vivo. We determined that A24 binds TfR with an equilibrium constant (K'd) of 2.7 nM and competes with transferrin for binding to TfR. A24 also inhibited [55Fe]-transferrin uptake in activated T cells and blocked T-cell proliferation. Moreover, A24 reduced and impaired TfR expression and recycling, respectively. Most important, we showed that A24 blocked the ex vivo proliferation of malignant T cells from both acute and chronic forms of ATL, through induction of programmed cell death. Therefore efficient therapeutic tools to treat acute forms of ATL might be derived from A24.