The clinical and economic costs associated with regional disparities in varicella vaccine coverage in Italy over 50 years (2020-2070).

Italy implemented two-dose universal varicella vaccination (UVV) regionally from 2003 to 2013 and nationally from 2017 onwards. Our objective was to analyze regional disparities in varicella outcomes resulting from disparities in vaccine coverage rates (VCRs) projected over a 50-year time-horizon (2020-2070). A previously published dynamic transmission model was updated to quantify the potential public health impact of the UVV program in Italy at the national and regional levels. Four 2-dose vaccine strategies utilizing monovalent (V) and quadrivalent (MMRV) vaccines were evaluated for each region: (A) MMRV-MSD/MMRV-MSD, (B) MMRV-GSK/MMRV-GSK, (C) V-MSD/MMRV-MSD, and (D) V-GSK/MMRV-GSK. Costs were reported in 2022 Euros. Costs and quality-adjusted life-years (QALYs) were discounted 3% annually. Under strategy A, the three regions with the lowest first-dose VCR reported increased varicella cases (+ 34.3%), hospitalizations (+ 20.0%), QALYs lost (+ 5.9%), payer costs (+ 22.2%), and societal costs (+ 14.6%) over the 50-year time-horizon compared to the three regions with highest first-dose VCR. Regions with low first-dose VCR were more sensitive to changes in VCR than high first-dose VCR regions. Results with respect to second-dose VCR were qualitatively similar, although smaller in magnitude. Results were similar across all vaccine strategies.

Convolutional LSTM model for cine image prediction of abdominal motion.

Objective.In this study, we tackle the challenge of latency in magnetic resonance linear accelerator (MR-Linac) systems, which compromises target coverage accuracy in gated real-time radiotherapy. Our focus is on enhancing motion prediction precision in abdominal organs to address this issue. We developed a convolutional long short-term memory (convLSTM) model, utilizing 2D cine magnetic resonance (cine-MR) imaging for this purpose.Approach.Our model, featuring a sequence-to-one architecture with six input frames and one output frame, employs structural similarity index measure (SSIM) as loss function. Data was gathered from 17 cine-MRI datasets using the Philips Ingenia MR-sim system and an Elekta Unity MR-Linac equivalent sequence, focusing on regions of interest (ROIs) like the stomach, liver, pancreas, and kidney. The datasets varied in duration from 1 to 10 min.Main results.The study comprised three main phases: hyperparameter optimization, individual training, and transfer learning with or without fine-tuning. Hyperparameters were initially optimized to construct the most effective model. Then, the model was individually applied to each dataset to predict images four frames ahead (1.24-3.28 s). We evaluated the model's performance using metrics such as SSIM, normalized mean square error, normalized correlation coefficient, and peak signal-to-noise ratio, specifically for ROIs with target motion. The average SSIM values achieved were 0.54, 0.64, 0.77, and 0.66 for the stomach, liver, kidney, and pancreas, respectively. In the transfer learning phase with fine-tuning, the model showed improved SSIM values of 0.69 for the liver and 0.78 for the kidney, compared to 0.64 and 0.37 without fine-tuning.Significance. The study's significant contribution is demonstrating the convLSTM model's ability to accurately predict motion for multiple abdominal organs using a Unity-equivalent MR sequence. This advancement is key in mitigating latency issues in MR-Linac radiotherapy, potentially improving the precision and effectiveness of real-time treatment for abdominal cancers.

Identifying clinically relevant sources of variability: The clopidogrel challenge.

High interindividual variability in clinical outcomes following clopidogrel's standard dosing regimen continues to be a challenge even two decades after its approval. CYP2C19 polymorphisms, obesity, older age, diabetes, and drug-drug interactions have been identified as risk factors for adverse events and treatment failure. We conducted a mechanism-based pharmacokinetic/pharmacodynamic analysis, where we integrated knowledge on in vitro enzyme kinetic, physiological, genetic, and demographic information to characterize changes in platelet reactivity from baseline following clopidogrel antiplatelet therapy. When considering the combined impact of these covariates, our analysis results indicate that higher maintenance doses are required for CYP2C19 intermediate metabolizers and poor metabolizers compared to extensive metabolizers and that respective maintenance doses have to be further increased for obese subjects for each of these CYP2C19 phenotypes. In addition, interindividual differences in the fraction absorbed and the CES1 activity were identified as sources of interindividual differences in clopidogrel's active metabolite concentrations and, thus, platelet reactivity.

High prevalence of class 1 integrons in clinical isolates of methicillin-resistant Staphylococcus aureus from India.

INTRODUCTION: Class1 integrons are one of the prevalent mechanisms of antibiotic resistance gene transfer in Gram-negative organisms, but their prevalence and role in the spread of antibiotic resistance genes in methicillin-resistant Staphylococcus aureus (MRSA) is unexplored. The purpose of this study was to investigate the prevalence of class 1 integrons in clinical isolates of MRSA. MATERIALS AND METHODS: Total 143 MRSA isolates obtained from two different cities in India (Pune and Mumbai) were characterized by biochemical tests, and the antibiotic sensitivity was performed using the Clinical and Laboratory Standards Institute (CLSI) guidelines. The presence of class 1 integrons, sul1/qacE0Δ1 region of class 1 integron and mecA gene among these isolates was determined by polymerase chain reaction (PCR). RESULTS: All 143 isolates were mecA positive and coagulase-positive. Overall, 71% of the MRSA isolates carried class 1 integrons; 58% (45/77) of the isolates obtained from Mumbai and 85% (56/66) of the isolates from Pune carried class 1 integrons. In all, 39% of these isolates carried sul1/qacEΔ1 region, thus confirming the association of class 1 integrons with antibiotic resistance genes. Along with ß-lactam antibiotics the MRSA isolates were resistant to several other antibiotics, with resistance to erythromycin, ciprofloxacin and trimethoprim-sulfamethoxazole being observed in 75%, 66% and 60% of the isolates, respectively. CONCLUSION: To the best of our knowledge, this is the first report of class 1 integrons in MRSA isolates from India. The study provides insights into the prevalence of a novel mechanism adapted by MRSA for the propagation of antibiotic resistance genes.

Radiation-induced sarcoma masquerading as osteoradionecrosis: case report and literature review.

BACKGROUND: Radiation therapy is a commonly used treatment in head and neck oncology, whether used alone or as an adjunct to other treatments. Osteoradionecrosis and radiation-induced malignancy are both rare, late complications of radiation therapy. METHODS: This paper describes a case of radiation-induced sarcoma of the mandible initially presenting as osteoradionecrosis. In addition, the literature on the identification and treatment of these entities is reviewed. RESULTS: The patient underwent excision and reconstruction of the presumed osteoradionecrosis. Final pathology demonstrated radiation-induced sarcoma. The patient suffered tumour recurrence at seven months post-operatively. CONCLUSION: When evaluating a patient with osteoradionecrosis, clinicians should be cognisant of the risk of malignancy. This paper describes the first case of radiation-induced sarcoma presenting as osteoradionecrosis. Primary treatment of radiation-induced sarcoma is wide surgical extirpation, with a very limited role for chemotherapy. Overall survival for this entity is poor.

Immunological profiling in chronic rhinosinusitis with nasal polyps reveals distinct VEGF and GM-CSF signatures during symptomatic exacerbations.

BACKGROUND: The mechanisms and immune pathways associated with chronic rhinosinusitis (CRS) are not fully understood. Immunological changes during acute exacerbation of CRS may provide valuable clues to the pathogenesis and perpetuation of the disease. OBJECTIVE: To characterize local and systemic immune responses associated with acute worsening of sinonasal symptoms during exacerbation in CRS with nasal polyps (CRSwNP) compared to controls. METHODS: This was a non-interventional prospective study of individuals with CRSwNP and normal controls. Subjects underwent a baseline visit with collection of nasal secretions, nasal washes, and serum specimens. Within 3 days of acute worsening of sinonasal symptoms, subjects underwent a study visit, followed by a post-visit 2 weeks later. The sinonasal outcome test-22 (SNOT-22) scores and immunological parameters in the specimens were analysed using a novel, unsupervised learning method and by conventional univariate analysis. RESULTS: Both CRSwNP patients and control subjects showed a significant increase in SNOT-22 scores during acute exacerbation. Increased nasal levels of IL-6, IL-5, and eosinophil major basic protein were observed in CRSwNP patients. A network analysis of serum specimens revealed changes in a set of immunological parameters, which are distinctly associated with CRSwNP but not with controls. In particular, systemic increases in VEGF and GM-CSF levels were notable and were validated by a conventional analysis. CONCLUSIONS: CRSwNP patients demonstrate distinct immunological changes locally and systemically during acute exacerbation. Growth factors VEGF and GM-CSF may be involved in the immunopathogenesis of subjects with CRS and nasal polyps experiencing exacerbation.

The risk of asthma exacerbation after reducing inhaled corticosteroids: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Asthma guidelines suggest reducing controller medications when asthma is stable. METHODS: The purpose of the study is to estimate the risk of asthma exacerbation in stable asthmatics who reduce inhaled corticosteroids (ICS) compared to those who maintain a stable ICS dose. We identified articles from a systematic review of English and non-English articles using MEDLINE, EMBASE, Web of Science, and CENTRAL (inception to May 25, 2013). We included randomized controlled trials (RCTs) with a stable asthma run-in period of 4 weeks or more, an intervention to reduce ICS, and a follow-up period of at least 3 months. RESULTS: The search strategy identified 2253 potential articles, of which 206 were reviewed at the full-text level and 6 met criteria for inclusion. The relative risk of an asthma exacerbation in individuals who reduced ICS compared to those who maintained the same ICS dose was 1.25 (95% CI 0.96, 1.62; P = 0.10; I(2)  = 0%) in studies with a mean follow-up of 22 weeks. Individuals who reduced ICS had a decreased% predicted FEV1 of 0.87% (95% CI -1.58%,3.33%; P = 0.49, I(2)  = 58%) and a decreased mean morning peak expiratory flow of 9.57 l/min (95% CI 1.25, 17.90; P = 0.02; I(2)  = 74%) compared to those individuals who maintained a stable ICS dose. CONCLUSIONS: Asthma exacerbations were statistically no more likely among individuals who reduced ICS compared to those who maintained their ICS dose, supporting current guidelines which recommend decreasing ICS by 50% after a period of asthma stability.

Validity of the line-pair bar-pattern method in the measurement of the modulation transfer function (MTF) in megavoltage imaging.

The measurement of the modulation transfer function (MTF) of an imaging device is a common requirement in evaluating radiographic detector performance. Such measurements are considered mandatory in detector development research, and may also be carried out as part of routine quality assurance (QA) checks of image quality. Traditionally, MTF measurement has been performed by imaging either a narrow slit or a sharp edge in order to generate a line spread function, whose Fourier transform provides the MTF on a near-continuous frequency domain. Much less commonly employed is the method of square-wave line-pair modulations, in which the modulation response to bar resolution targets contained in a bar pattern is used to estimate the MTF at discrete spatial frequencies. While the slit and edge methods offer advantages of accuracy and a well-know standardized protocol for measurement based on several decades of development, their major limitation is the difficult and time-consuming experimental setup that is necessary to ensure accurate measurements. On the other hand, the bar pattern offers the advantage of a quick, simple, and easy measurement without the need for a complex experimental setup, with the main disadvantages of the technique being a pseudo-normalization that may lead to an overestimated MTF, and corrections for removing higher-order frequency harmonics that require interpolating between discrete spatial frequencies. Therefore, bar patterns are traditionally used for qualitative imaging applications like detector QA in terms of relative and arbitrarily defined spatial resolution metrics, while slit and edge methods are preferred for quantitative MTF measurements. Compared to diagnostic x rays, MTF measurements using megavoltage x rays are further complicated by low x-ray attenuation and excessive Compton scattering. In this work, a method to measure the MTF of megavoltage x-ray detectors based on imaging square-wave line pairs with improved near-zero-frequency normalization was developed as an adaptation to previously reported methods. Monte Carlo simulations were used to identify an improved normalization condition with which the accuracy of the MTF determined from line-pair modulations could be enhanced considerably compared to previously used techniques. Slit, edge, and bar-pattern measurements were performed to obtain the MTF of commercial megavoltage imaging devices including portal film and electronic portal imaging devices. A comparison of the MTF measurements from the three techniques was used to ascertain the validity of the proposed bar-pattern method for accurate and reliable measurement of MTF for megavoltage imagers. Statistical analyses revealed no significant differences between the bar-pattern method and the standard slit and edge techniques, indicating very good agreement (mean difference within +/- 3%). These results indicated the potential for line-pair bar patterns to be used more effectively than in the past for traditional QA imaging as well as for quantitative MTF measurement in detector development research.

Effect of recombination in a high quantum efficiency prototype ionization-chamber-based electronic portal imaging device.

The quantum efficiency (QE) of an imaging detector can be increased by utilizing a thick, high-density detection medium to increase the number of quantum interactions. However, image quality is more accurately described by the detection quantum efficiency (DQE). If a significant fraction of the increase in the number of detected quanta from a thick, dense detector were to result in useful imaging signal, this represents a favorable case where enhanced QE leads to increased DQE. However, for ionization-type detectors, one factor that limits DQE is the recombination between ion pairs that acts as a secondary quantum sink due to which enhancement in QE may not result in higher DQE depending on the extent of the signal loss from recombination. Therefore, an analysis of signal loss mechanisms or quantum sinks in an imaging system is essential for validating the overall benefit of high QE detectors. In this paper, a study of ion recombination as a secondary quantum sink is presented for a high QE prototype ion-chamber-based electronic portal imaging device (EPID): the kinestatic charge detector (KCD). The KCD utilizes a high pressure noble gas (krypton or xenon at 100 atm) and an arbitrarily large detector thickness (of the order of centimeters), resulting in a high QE imager. Compared with commercial amorphous silicon flat panel imagers that provide DQE(0) approximately 0.01, the KCD has much higher DQE. Studies indicated that DQE(0) = 0.20 for 6.1 cm thick, 100 atm (rho = 3.4 g/cm3) xenon chamber, and DQE(0)=0.34 for a 9.1 cm thick chamber. A series of experiments was devised and conducted to determine the signal loss due to recombination for a KCD chamber. The measurements indicated a fractional recombination loss of about 14% for a krypton chamber and about 18% for a xenon chamber under standard operating conditions (100 atm chamber pressure and 1275 V/cm electric field intensity). A theoretical treatment of the effect of recombination on imaging signal-to-noise ratio was applied to quantify the loss in DQE. These calculations indicated that recombination had a limited effect (<2%) on DQE under standard operating conditions. This was validated by good agreement between experimentally measured DQE and that obtained using Monte Carlo simulations that did not account for recombination.

The molecular basis of "curlicue": a sperm motility abnormality linked to the sterility of t haplotype homozygous male mice.

The t complex, a variant region of chromatin occupying approximately 40-million base pairs of proximal chromosome 17, exists in natural populations of wild mice of the Mus musculus species as a family of homologues called t haplotypes (t). Relative to wild-type (+) homologues, all t haplotypes share four large non-overlapping inversions, spanning 95% of the region, leading to intra-inversion recombination suppression in +/t heterozygotes. Non-lethal t homozygous males or complementing recessive lethal t doubly heterozygous males (hereafter both abbreviated "t/t males") are invariably and completely sterile, due to expression of several sperm function abnormalities. One of these traits, "curlicue", describes a condition in which spermatozoa from t/t males fail to reach the site of fertilization in vivo because they exhibit a severe loss of vigorous forward motility due to the chronic negative curvature of their flagella. Current data indicate that "curlicue" is the complex phenotypic reflection of the expression of three or more mutations clustered in the distal one-third of the largest and most-distal t complex inversion, In(17)4. From proximal to distal, candidates include Dnahc8, Tsga2 and Tctex5. Interestingly, new results from high-resolution intra-inversion genetic mapping and protein localization studies suggest that the products of the distal two candidates, Tsga2 and Tctex5, might play synergic roles in the expression of both the "curlicue" motility abnormality and the "stop" sperm-egg interaction aberration, regarded as functionally unrelated traits.

Is the functional decline of Parkinson's disease similar to the functional decline of Alzheimer's disease?

Since many Parkinson's disease (PD) subjects develop dementia, we determined whether the correlation between functional and cognitive decline seen in Alzheimer's disease (AD) is seen in PD. Seventy-five PD subjects with and without dementia and 103 AD/MCI subjects underwent the Functional Assessment Staging (FAST), the Global Deterioration Scale (GDS), the UPDRS motor portion, and the MMSE. In AD/MCI subjects, changes in FAST and GDS scores correlated with MMSE (rho=-0.814, P<0.001; rho=-0.840, P<0.001, respectively). In PD subjects, the FAST and GDS also correlated with MMSE (rho=-0.675, P<0.001; rho=-0.647, P<0.001, respectively). The UPDRS correlated with the GDS and FAST more closely in PD than in AD. Similar to AD, functional declines in PD correlates with cognitive decline and may be influenced by motor disability in PD.

Oxidation of alkylarenes using aqueous potassium permanganate under cavitation: comparison of acoustic and hydrodynamic techniques.

Various alkylarenes were oxidized to the corresponding aryl carboxylic acids using aqueous potassium permanganate under heterogeneous condition in the presence of hydrodynamic cavitation and the results of the reaction have been compared with the acoustic cavitation in terms of their energy efficiency. The rate of reaction was determined for each reaction. In the oxidation of p-xylene, seven times more product could be obtained in the case of hydrodynamic cavitation than in the case of acoustic cavitation. The reaction was found to be considerably accelerated at ambient temperature.

Oxidation of alkylarenes to the corresponding acids using aqueous potassium permanganate by hydrodynamic cavitation.

Oxidation of toluene using aqueous potassium permanganate was studied under heterogeneous condition in the presence of hydrodynamic cavitation and compared with the results of the reaction under acoustic cavitation. Various parameters, such as quantity of potassium permanganate, toluene to aqueous phase ratio, reaction time and cavitation parameters such as orifice plate, and pump discharge pressure were optimized. The reaction was found to be considerably accelerated at ambient temperature in the presence of cavitation. On comparison, it was found that when 1 kJ of energy was passed to the reaction mixture in the case of acoustic cavitation, the product obtained was 4.63 x 10(-6) mol, whereas when 1 kJ of energy was passed to the reaction mixture in the case of hydrodynamic cavitation the product obtained was 2.70 x 10(-5) mol. Hence, about six times more product would be obtained in the case of hydrodynamic cavitation than in the case of acoustic cavitation at same energy dissipation. It has been observed that further optimization is possible.

On modelling the kinestatic charge detector for digital radiographic diagnostic and portal imaging.

The kinestatic charge detection (KCD) principle has been a digital radiography technique for more than a decade. The advances of the KCD technique have gone from diagnostic imaging to portal imaging. However, little work has been done on understanding the selection of key KCD parameters and relationships between them. In the present study, an engineering model was established that could be used to optimize the placements of key parameters in terms of KCD system mechanical design. In the proposed KCD engineering model, the basic energy conservation law was applied to the process of ion transmission. It allows for the computation of the KCD design parameters such as the optimum grid placement, high voltage board tilt angle and grid wire space, as well as to provide recommendations on high voltage board and electric potentials and their ratio.

Sonochemical bromination of acetophenones using p-toluenesulfonic acid-N-bromosuccinimide.

Substituted acetophenones react with N-bromosuccinimide (NBS) and p-toluenesulfonic acid (p-TsOH) in the presence of ultrasound in methanol at 35 +/- 2 degrees C to give alpha-bromoacetophenones in high yield. In the absence of ultrasound the reaction takes place at the boiling point of methanol (65 degrees C) and takes longer time. The reaction does not take place in the absence of p-TsOH thermally or sonically. However the reaction is possible under photochemical conditions in the absence of p-TsOH. The best solvent for the reaction was found to be methanol.

Sonochemical chloro-oxidation of phenols using HCl-H2O2.

The reaction of phenol, 2-nitrophenol, thymol, 1-naphthol and 1-hydroxy-2-naphthoic acid with HCl-H2O2 was carried out in the presence and in the absence of ultrasound. In the presence of ultrasound phenol, 2-nitrophenol and thymol gave only the chlorinated products, while 1-naphthol and 1-hydroxy-2-naphthoic acid gave chlorinated quinones as the major products. The reactions with ultrasound were compared with those without ultrasound.

Bone or cartilage invasion by advanced head and neck cancer: intra-arterial supradose cisplatin chemotherapy and concomitant radiotherapy for organ preservation.

BACKGROUND: Invasion of bony or cartilaginous structures by advanced upper aerodigestive tract cancer has been considered an indication for surgery on the basis of historic experience of poor responsiveness to radiation therapy. At University of Tennessee-Memphis, patients with advanced head and neck cancer have been treated on a protocol of concomitant intra-arterial (targeted) cisplatin and conventional radiation therapy. OBJECTIVE: To compare the efficacy, in terms of disease control and survival, of this protocol in patients with T4 squamous cell cancers and invasion of bony or cartilaginous structures (group 1; n = 45) vs those with T4 disease but no bone or cartilage involvement (group 2; n = 90). DESIGN: Subset analysis of protocol database and retrospective chart review. METHODS: Treatment consisted of 4 weekly intra-arterial infusions of cisplatin (150 mg/m(2) per week), with simultaneous systemic neutralization by intravenous sodium thiosulfate (9 mg/m(2)), and concurrent radiation therapy at 180 rad (1.8 Gy) or 200 rad (2 Gy) per fraction to a planned total of 6600 to 7400 rad (66-74 Gy) to the primary site or overt nodal disease. Presence of bone or cartilage invasion was established by review of tumor diagrams of clinical findings and computed tomography or magnetic resonance imaging reports. RESULTS: Of 135 patients who had T4 disease and a minimum follow-up of 9 months (median, 40 months), 45 had clinical or radiologic evidence of bone (n = 29: mandible, 12; maxilla, 9; sphenoid, 3; hyoid, 6) and/or cartilage (n = 18: thyroid, 16; cricoid, 4) invasion (some patients had involvement of more than 1 site). The rate of complete response in group 1 (66.7%) was not significantly different from that in group 2 (71.1%) (chi(2) test, P = .79). The 2-year overall actuarial survival for group 1 (46.3%; 95% confidence interval, 30.3%-62.3%) was not significantly different (generalized Wilcoxon test, P = .36) from that of group 2 (36.9%; 95% confidence interval, 25.5%-48.4%). A marked trend was noted for higher response rates in cases of cartilage invasion (81.2%) than in those with bone invasion (58.6%) (P = .15). CONCLUSION: Equivalent efficacy of treatment in the 2 groups suggests that targeted chemoradiation can be a definitive therapeutic option in patients with advanced head and neck cancer invading bony or cartilaginous structures.

Rationale for intralesional valrubicin in chemoradiation of squamous cell carcinoma of the head and neck.

OBJECTIVES/HYPOTHESIS: With some advanced squamous cell carcinomas (SCCs) of the head and neck, chemoradiation therapy may obviate the need for surgical intervention. However, both modalities are known to produce organ toxicities, and tumor insensitivity remains problematic. Thus there is a clear need for the development of new treatment strategies. Accordingly, preclinical studies to evaluate the use of valrubicin, a contact-safe, mechanistically novel antitumor agent, combined with low-dose radiation for the therapy of SCC have been conducted. METHODS: The comparative in vitro antitumor activities of valrubicin with or without irradiation versus cisplatin were evaluated using human-derived sensitive and cisplatin-resistant SCC cell lines. A hamster cheek pouch model of SCC was used to assess the efficacy of weekly intratumoral valrubicin injections with and without concurrent low-dose irradiation. RESULTS: Valrubicin cytotoxicity was found to be comparable in both sensitive and platinum-resistant cell lines and superior to cisplatin. The addition of minimally cytotoxic cell irradiation (300-450 cGy) resulted in prolonged G2/M cell cycle arrest and a supraadditive increase in apoptotic cell death. In hamsters, once a week x 3 intratumoral drug injections (3, 6, or 9 mg) were growth inhibitory; however, when valrubicin (6 mg) was combined with minimally cytotoxic irradiation (150, 250, or 350 cGy) significant tumor shrinkage was observed. CONCLUSIONS: Valrubicin produces supra-additive effects against SCC when combined with low-dose irradiation. This effect appears to correlate with the ability of valrubicin, a cytoplasmic-localizing drug, to inhibit protein kinase C. Therapeutic use of valrubicin against SCC could provide for reduced radiation doses with consequent improved efficacy and reduction in host toxicity.

Comparison of two immobilization techniques using portal film and digitally reconstructed radiographs for pediatric patients with brain tumors.

PURPOSE: To compare the accuracy of two immobilization techniques for pediatric brain tumor patients. METHODS AND MATERIALS: We analyzed data from 128 treatments involving 22 patients. Patients were immobilized with either a relocatable head frame (12 patients) or a vacuum bag (10 patients). Orthogonal portal films were used as verification images. Errors in patient positioning were measured by comparing verification images with digitally reconstructed radiographs generated by a three-dimensional treatment-planning system. RESULTS: With the head frame, systematic errors ranged from 1.4 mm to 2.1 mm; random errors, from 1.7 mm to 2.1 mm. With the vacuum bag, systematic errors ranged from 2.1 mm to 2.5 mm; random errors, from 2.0 mm to 2.6 mm. For the head frame, the mean length of the radial displacement was 4.4 mm; 90% of the total three-dimensional deviation was less than 6.8 mm. The corresponding values for the vacuum bag were 5.0 and 6.6 mm, respectively. CONCLUSIONS: The head frame and vacuum bag techniques limit the random and systematic errors in each of the three directions to within +/- 5 mm. We have used these results to determine the margin used to create the planning target volume for conformal radiation therapy.

An axonemal dynein at the Hybrid Sterility 6 locus: implications for t haplotype-specific male sterility and the evolution of species barriers.

Poor sperm motility characterized by a distinct aberration in flagellar waveform known as "curlicue" is a hallmark of t haplotype (t) homozygous male sterility. Previous studies have localized "curlicue" and a flagellar developmental defect, "whipless", to the Hybrid Sterility 6 locus (Hst6), between the markers Pim1 and Crya1. More recent heterospecific breeding experiments between Mus spretus (Spretus) and Mus musculus domesticus (Domesticus) have mapped the primary source(s) of both "curlicue" and "whipless" to a small sub-locus of Hst6, Curlicue a (Ccua). Here we report the complete physical isolation of the Ccua locus and the identification of a candidate gene for expression of both "whipless" and "curlicue" at its proximal end, an axonemal dynein heavy chain gene, Dnahc8, formerly mapped by interspecific backcross analysis near Pim1. Dnahc8 mRNA expression commences in the Domesticus wild-type testis just prior to flagellar assembly and is testis-specific in the adult male. However, expression of Dnahc8 is not readily evident in the testis of either Spretus or "whipless" animals (Domesticus males homozygous for the Spretus allele of Dnahc8). Our results argue that Dnahc8 is fundamental to flagellar organization and function in Domesticus, but not Spretus, and suggest that Dnahc8 is integral to both Hst6- and t-specific male infertility.