An audit of endoscopic third ventriculostomy (ETV) in a regional paediatric neurosurgical centre assessing the accuracy and feasibility of the ETV success score.

BACKGROUND: Endoscopic third ventriculostomy success score (ETVss) is widely utilised to predict outcomes for ETV. Accurate prediction of success for a procedure is of vital importance both for selecting the optimal management plan and for obtaining informed consent. Existing literature demonstrates a variety of opinions on the accuracy of the currently utilised ETVss and recommends a range of techniques to reduce the number of subsequent ventriculo-peritoneal (VP)-shunt insertions, prompting the present study. METHODS: We retrospectively analysed data for ETV cases since 2007 to review success rate in our regional paediatric neurosurgical centre and if the currently utilised ETVss successfully predicted outcomes. Failed ETV cases were defined as any patient who received a VP-shunt at any time following ETV. Data was analysed with MS ExcelR and RStudioR. RESULTS: 44 ETVs were performed over 13 years with approximately equal distribution between male and female patients; median age 7 years (IQR 4-13 years). Overall, mean ETVss for these 44 procedures was 78%; actual success rate was 70% with no statistically significant difference between them (p = 0.286; Welch two sample t-test). Accuracy of ETVss varied with pathology: tectal gliomas (mean ETVss 75% and actual success 78%); cerebellar tumours (mean ETVss 85% and actual success 81%); other tumours (mean ETVss 75% and actual success 81%); aqueduct stenosis (mean ETVss 71% and actual success 69%); and other pathologies (mean ETVss 70% and actual success 60%). < 1 month and 1-6 months and 1-10 years and > 10 years contributed equally to the accuracy of ETVss. CONCLUSION: Non-telencephalon tumours and obstruction at the level of the mid-brain are most strongly associated with successful ETV outcome. These findings can be used to modify the currently utilised ETVss to further improve accuracy of outcome prediction. We recommend a modified-ETVss (m-ETVss) and a future larger adequately powered prospective study to validate this.

A unique schedule of palonosetron, ondansetron, and dexamethasone for the prevention of delayed nausea and vomiting in patients receiving myeloablative chemotherapy.

Myeloablative chemotherapy administered prior to autologous stem cell transplantation (auto-SCT) is associated with a significant amount of chemotherapy-induced nausea and vomiting (CINV). We conducted a phase II trial to assess the safety, efficacy, and impact on quality of life when palonosetron (PAL) 0.25 mg combined with dexamethasone were given on the final or only day of myeloablative chemotherapy for auto-SCT. The primary end point of this study was the incidence of achieving a delayed CINV complete response defined as no emetic episode and no use of rescue medications during the 24-120 h period post chemotherapy. Eighty-five patients were enrolled in the study and received PAL. A delayed CINV complete response was achieved in 15% of patients. A multivariate analysis demonstrated no associated differences between age, gender, diagnosis, or regimen. By day 5 after PAL, the mean nausea severity was 0.91 ± 2.45 vs. 0.09 ± 1.58 at baseline (p = 0.012). Quality of life measurements demonstrated similar quality of life between baseline and day 3. By day 6 however, nausea alone had a statistically significant impact on quality of life. In our study, PAL controlled nausea severity and sustained quality of life, but further strategies are needed to control delayed CINV associated with the auto-SCT process.

Risk factors for morphoea disease severity: a retrospective review of 114 paediatric patients.

BACKGROUND: Morphoea is a rare fibrosing disease of the skin and subcutaneous tissue with an unpredictable disease course, running the spectrum from mild skin involvement to severe disfigurement or extracutaneous complications. OBJECTIVES: Our objective was to describe the natural history of paediatric morphoea and determine patient variables that were associated with severe disease. PATIENTS AND METHODS: We conducted a retrospective chart review of patients with morphoea seen in one paediatric hospital system. Information about demographics, clinical characteristics, disease course and treatment were collected. Statistical analysis was performed using appropriate univariate tests and a multivariable model. RESULTS: One hundred and fourteen patients met study inclusion criteria. The female : male ratio was 2·6 : 1, and the median age of onset was 7 years old. There were 55 patients (48%) with linear morphoea, 38 patients (33%) with circumscribed morphoea, 12 patients (11%) with generalized morphoea, and nine patients (8%) with mixed morphoea. Neurological symptoms and joint involvement were present in 27 subjects (24%). Extracutaneous manifestations occurred in 38% of subjects with linear morphoea, compared with 15% with generalized morphoea and 3% with circumscribed morphoea (P = 0·0001). Thirty-six per cent of children with disease onset prior to 10 years of age and 5% of children with disease onset after 10 years of age had extracutaneous manifestations (P = 0·0002). Both linear morphoea and early-onset disease were significantly associated with extracutaneous involvement in a multivariable model. CONCLUSIONS: Children with linear morphoea and disease onset before 10 years of age should be monitored closely for extracutaneous manifestations and need early treatment with systemic medications to prevent disease complications.

Demographic and clinical characteristics of cutaneous lupus erythematosus at a paediatric dermatology referral centre.

BACKGROUND: Paediatric cutaneous lupus erythematosus (CLE) is uncommon and inadequately described in the literature. Similar to adults, children with CLE develop LE-specific and/or LE-nonspecific skin findings. Similarities and differences in demographics and clinical course between paediatric and adult CLE have not been sufficiently described. OBJECTIVES: To detail the demographic and clinical features of paediatric CLE and compare these findings with those reported in the adult literature. METHODS: A retrospective chart review was performed of 53 children seen in a paediatric dermatology clinic with cutaneous manifestations of LE. RESULTS: Patients presented with all five major subtypes of CLE, with some notable differences from adult CLE and previously published reports of paediatric CLE. Progression from discoid LE to systemic LE (SLE) did not occur in our cohort. Patients with subacute CLE were more likely than adults to have lesions below the waist as well as concomitant SLE. Sex distribution for CLE in our study was equal prior to puberty and female predominant in post-pubertal patients. CONCLUSIONS: Children with CLE have variable clinical presentations and progression to SLE that may be different from adult disease. Specifically, children with acute and subacute CLE may be more likely than adults to have systemic disease; therefore, patients with these subtypes should be monitored closely for evidence of SLE. Study limitations included small patient numbers that may limit the ability to generalize these data and relatively short follow-up intervals.

Ecohydrological and socioeconomic integration for the operational management of environmental flows.

Investment in and operation of flow control infrastructure such as dams, weirs, and regulators can help increase both the health of regulated river ecosystems and the social values derived from them. This requires high-quality and high-resolution spatiotemporal ecohydrological and socioeconomic information. We developed such an information base for integrated environmental flow management in the River Murray in South Australia (SA). A hydrological model was used to identify spatiotemporal inundation dynamics. River ecosystems were classified and mapped as ecohydrological units. Ecological response models were developed to link three aspects of environmental flows (flood duration, timing, and inter-flood period) to the health responses of 16 ecological components at various life stages. Potential infrastructure investments (flow control regulators and irrigation pump relocation) were located by interpreting LiDAR elevation data, digital orthophotography, and wetland mapping information; and infrastructure costs were quantified using engineering cost models. Social values were quantified at a coarse scale as total economic value based on a national survey of willingness-to-pay for four key ecological assets; and at a local scale using mapped ecosystem service values. This information was integrated using a constrained, nonlinear, mixed-integer, compromise programming optimization model and solved using a stochastic Tabu search algorithm. We tested the model uncertainty and sensitivity using 390 Monte Carlo model runs at varying weights of ecological health vs. social values. Integrating ecohydrological and socioeconomic information identified environmental flow management regimes that efficiently achieved both ecological and social objectives. Using an ecologically weighted efficient and socially weighted efficient scenario, we illustrated model outputs including a suite of cost-effective infrastructure investments and an operational plan for new and existing flow control structures including dam releases, weir height manipulation, and regulator operation on a monthly time step. Both the investments and management regimes differed substantially between the two scenarios, suggesting that the choice of weightings on ecological and social objectives is important. This demonstrates the benefit of integrating high-quality and high-resolution spatiotemporal ecohydrological and socioeconomic information for guiding the investment in and operational management of environmental flows.

A high observed substitution rate in the human mitochondrial DNA control region.

The rate and pattern of sequence substitutions in the mitochondrial DNA (mtDNA) control region (CR) is of central importance to studies of human evolution and to forensic identity testing. Here, we report a direct measurement of the intergenerational substitution rate in the human CR. We compared DNA sequences of two CR hypervariable segments from close maternal relatives, from 134 independent mtDNA lineages spanning 327 generational events. Ten substitutions were observed, resulting in an empirical rate of 1/33 generations, or 2.5/site/Myr. This is roughly twenty-fold higher than estimates derived from phylogenetic analyses. This disparity cannot be accounted for simply by substitutions at mutational hot spots, suggesting additional factors that produce the discrepancy between very near-term and long-term apparent rates of sequence divergence. The data also indicate that extremely rapid segregation of CR sequence variants between generations is common in humans, with a very small mtDNA bottleneck. These results have implications for forensic applications and studies of human evolution.

Sinks for nitrogen inputs in terrestrial ecosystems: a meta-analysis of 15N tracer field studies.

Effects of anthropogenic nitrogen (N) deposition and the ability of terrestrial ecosystems to store carbon (C) depend in part on the amount of N retained in the system and its partitioning among plant and soil pools. We conducted a meta-analysis of studies at 48 sites across four continents that used enriched 15N isotope tracers in order to synthesize information about total ecosystem N retention (i.e., total ecosystem 15N recovery in plant and soil pools) across natural systems and N partitioning among ecosystem pools. The greatest recoveries of ecosystem 15N tracer occurred in shrublands (mean, 89.5%) and wetlands (84.8%) followed by forests (74.9%) and grasslands (51.8%). In the short term (< 1 week after 15N tracer application), total ecosystem 15N recovery was negatively correlated with fine-root and soil 15N natural abundance, and organic soil C and N concentration but was positively correlated with mean annual temperature and mineral soil C:N. In the longer term (3-18 months after 15N tracer application), total ecosystem 15N retention was negatively correlated with foliar natural-abundance 15N but was positively correlated with mineral soil C and N concentration and C:N, showing that plant and soil natural-abundance 15N and soil C:N are good indicators of total ecosystem N retention. Foliar N concentration was not significantly related to ecosystem 15N tracer recovery, suggesting that plant N status is not a good predictor of total ecosystem N retention. Because the largest ecosystem sinks for 15N tracer were below ground in forests, shrublands, and grasslands, we conclude that growth enhancement and potential for increased C storage in aboveground biomass from atmospheric N deposition is likely to be modest in these ecosystems. Total ecosystem 15N recovery decreased with N fertilization, with an apparent threshold fertilization rate of 46 kg N x ha(-1) x yr(-1) above which most ecosystems showed net losses of applied 15N tracer in response to N fertilizer addition.

Valproate in children with newly diagnosed idiopathic generalized epilepsy.

OBJECTIVES: Sparse information on dose-response characteristics for initial antiepileptic drug monotherapy in children with idiopathic generalized epilepsy (IGE) is available. The aim of this study is to characterize the therapeutic dose of valproate in children with newly diagnosed IGE. MATERIALS AND METHODS: Effect of initial valproate monotherapy and doses associated with seizure freedom were examined in consecutive children with IGE identified from a New Onset Seizure Clinic. RESULTS: Of 84 patients identified, 48 (57%) became seizure-free on valproate monotherapy and another 10 patients became seizure-free but discontinued VPA because of adverse effects. The mean dose in seizure-free children was 15.7 mg/kg/day and over 95% of IGE patients will respond below 25 mg/kg/day. CONCLUSIONS: Half of children became seizure-free on valproate monotherapy and did so at modest doses.

Developmental alteration in GABAA receptor structure and physiological properties in cultured cerebellar granule neurons.

Although we now have extensive knowledge about the GABAA receptor subunits determining benzodiazepine modulation of channel function, little is known about subunits influencing other modulatory sites on the GABAA receptor-chloride channel complex. We have identified a developmental change in subunit composition of the GABAA receptor in cultured cerebellar granule neurons that eliminates benzodiazepine-mediated enhancement of GABA responses and alters modulation by a substituted gamma-butyrolactone. Based on data from sequential PCR experiments, we mimicked the functional properties of early and mature receptors with heterologous expression of specific subunit combinations. This report describes one of the most extensive cell- and site-specific developmental changes for an ion channel seen to date.

P2X receptor characterization and IL-1/IL-1Ra release from human endothelial cells.

BACKGROUND AND PURPOSE: The pro-inflammatory cytokine, interleukin-1beta (IL-1beta), has been implicated in the pathogenesis of atherosclerosis, potentially via its release from vascular endothelium. Endothelial cells (EC) synthesize IL-1beta in response to inflammatory stimuli, but the demonstration and mechanism of release of IL-1 from ECs remains unclear. In activated monocytes, efficient release of bioactive IL-1beta occurred via activation of ATP-gated P2X(7) receptors (P2X(7)Rs). Activation of P2X(7)R in ECs from human umbilical vein (HUVECs) released IL-1 receptor antagonist (IL-1Ra). The purpose of this study was to provide a quantitative investigation of P2XR expression and function, in parallel with IL-1beta and IL-1Ra synthesis, processing and release, in HUVECs under pro-inflammatory conditions. EXPERIMENTAL APPROACH: Quantitative RT-PCR, immunoblotting, ELISA, flow cytometry, and whole-cell patch clamp recordings were used to determine protein expression and receptor function. IL-8-luciferase-reporter was used as an IL-1 sensitive bioassay. KEY RESULTS: HUVECs expressed P2X(4)R and P2X(7)R subtypes and both were significantly up-regulated under inflammatory conditions. P2X(7)R currents were increased 3-fold by inflammatory stimuli, whereas no P2X(4)R-mediated currents were detected. Caspase-1, but not IL-1beta, was present intracellularly under basal conditions; inflammatory stimuli activated the synthesis of intracellular pro-IL-1beta and increased caspase-1 levels. Activation of P2X(7)Rs resulted in low-level release of bioactive IL-1beta and simultaneous release of IL-1Ra. The net biological effect of release was anti-inflammatory. CONCLUSIONS AND IMPLICATIONS: Endothelial P2X(7)Rs induced secretion of both pro- and anti-inflammatory IL-1 receptor ligands, the balance of which may provide a means for altering the inflammatory state of the arterial vessel wall.

Learning to listen to the organisational rhetoric of primary health and social care integration.

The sustained modernisation of the UK primary health care service has resulted in individuals and organisations having to develop more integrated ways of working. This has resulted in changes to the structure and functioning of primary care organisations, changes to the traditional workforce, and an increase in scope of primary care practice. These changes have contributed to what for many staff has become a constantly turbulent organisational and practice environment. Data from a three-year project, commissioned by the North West Development Agency is used to explore how staff involved in these changes dealt with this turbulence. Three hundred and fifty staff working within primary care participated in the study. A multimethods approach was used which facilitated an iterative analysis and data collection process. Thematic analysis revealed a high degree of congruence between the perceptions of all staff groups with evidence of a generally well-articulated, but often rhetorical view of the organisational and professional factors involved in how these changes were experienced. This rhetoric was used by individuals as a way of containing both the good and bad elements of their experience. This paper discusses how these defense mechanisms need to be recognised and understood by managers so that a more supportive organisational culture is developed.

Population assessment of tropical tuna based on their associative behavior around floating objects.

Estimating the abundance of pelagic fish species is a challenging task, due to their vast and remote habitat. Despite the development of satellite, archival and acoustic tagging techniques that allow the tracking of marine animals in their natural environments, these technologies have so far been underutilized in developing abundance estimations. We developed a new method for estimating the abundance of tropical tuna that employs these technologies and exploits the aggregative behavior of tuna around floating objects (FADs). We provided estimates of abundance indices based on a simulated set of tagged fish and studied the sensitivity of our method to different association dynamics, FAD numbers, population sizes and heterogeneities of the FAD-array. Taking the case study of yellowfin tuna (Thunnus albacares) acoustically-tagged in Hawaii, we implemented our approach on field data and derived for the first time the ratio between the associated and the total population. With more extensive and long-term monitoring of FAD-associated tunas and good estimates of the numbers of fish at FADs, our method could provide fisheries-independent estimates of populations of tropical tuna. The same approach can be applied to obtain population assessments for any marine and terrestrial species that display associative behavior and from which behavioral data have been acquired using acoustic, archival or satellite tags.

The visual field in toxoplasmic retinochoroiditis.

AIMS: To document loss of central field in patients with scars from toxoplasmic retinochoroiditis close to the disc after resolution of disease. METHODS: Patients with a clinical diagnosis of toxoplasmic retinochoroiditis were enrolled from four centres. Automated central visual field testing was performed when their disease had settled and retinal photographs of the lesions were taken. The type of central field defect (whether absolute or relative) and whether it broke out to the periphery were correlated with the size of the retinochoroidal scar and its proximity to the optic nerve head. RESULTS: 69 eyes were enrolled; 16 (26%) were discarded because of poor field performance. Of the 53 remaining eyes, 31 showed absolute defects and 20 relative defects. Scars within one disc diameter of the disc were more likely to be associated with absolute defects breaking out to the periphery. CONCLUSION: The scarring induced by toxoplasmic retinochoroiditis is associated with considerable field loss when it occurs close to the optic nerve head. Current treatment is unlikely to ameliorate this situation. The degree of visual field loss should be an outcome measure for future trials of the efficacy of treatment trials for the disease.

The spectrum of pheochromocytoma in hypertensive patients with neurofibromatosis.

We have found an appreciable number of pheochromocytomas in patients with neurofibromatosis and concurrent hypertension (ten of 18 cases). At diagnosis, the patient age range was 15 to 62 years, the clinical appearance of the neurofibromatosis did not predict who would and who would not have pheochromocytomas, but the age at diagnosis was helpful in that our younger patients tended to have causes of hypertension other than pheochromocytoma. However, several causes of hypertension may coexist. The biochemical findings were highly diagnostic. The pheochromocytomas secreted epinephrine as well as norepinephrine and resided in or next to the adrenal gland. Where pheochromocytoma is the cause of hypertension, its resection generally results in a better control of hypertension than that obtained in patients whose BPs were elevated from other unknown causes.

Binding of interferon-alpha and -beta to a component of the human type I interferon receptor expressed in simian cells.

The type I interferons (IFNs) are a family of homologous cytokines that compete for receptor binding. Past experiments with a cloned human IFN-alpha receptor component (designated herein as HuIFNAR-1) transfected into different cell backgrounds have given contradictory results in terms of binding and signalling after exposure of cells to different human type I IFNs. In order to investigate the binding specificity of human type I IFN subtypes to HuIFNAR-1, a cDNA encoding HuIFNAR-1 was transfected into simian COS cells. HuIFNAR-1 expression in COS cells, which was confirmed by Northern blot analysis, resulted in increased binding of 125I-labelled HuIFN-alpha 2 and -beta. These data support the participation of this receptor component in ligand binding, probably in association with other receptor components.

Interaction of thyroxine and estrogen on the expression of estrogen receptor alpha, cholecystokinin, and preproenkephalin messenger ribonucleic acid in the limbic-hypothalamic circuit.

To study thyroid hormone and estrogen interactions in the central nervous system (CNS), the expression of estrogen sensitive genes was examined within the limbic-hypothalamic circuit. Estrogen up-regulates the expression of reproductively relevant neuropeptide messenger RNAs (mRNAs) encoding cholecystokinin (CCK) and enkephalin, peptides that stimulate lordosis. Estrogen down-regulates the expression of the estrogen receptor alpha (ER alpha) mRNA in the nuclei of the circuit. We examined the possibility that thyroid hormone treatment would block the estrogen modulation of these messages. Estradiol benzoate (EB), EB + thyroxine (T4), T4, or oil were administered to ovariectomized, adult female rats for 10 days. Isotopic in situ hybridization histochemistry revealed that within the limbic-hypothalamic nuclei, levels of CCK and preproenkephalin (PPE) mRNA levels were significantly higher in EB and EB + T4-treated animals compared with T4 or oil-treated animals. ER alpha mRNA levels were low in EB treated animals, elevated in T4 or oil-treated animals and further elevated in EB + T4-treated animals. In summary, T4 treatment had neither an independent nor an antagonistic effect on estrogen induced expression of CCK or PPE mRNA in the circuit. However, T4 did prevent the normal estrogenic decrease of ER alpha mRNA levels in the nuclei of the limbic-hypothalamic circuit.

Sodium depresses arterial baroreceptor reflex function in normotensive humans.

Sodium may contribute to the pathogenesis of hypertension by impairing arterial baroreceptor reflex function. The objectives of this study were to 1) determine whether a high sodium diet depresses arterial baroreceptor reflex function in normotensive humans, and 2) determine whether alterations in baroreceptor reflex function are related to changes in arterial compliance. Seventeen normotensive men, aged 30 +/- 2 years, received 10 and 200 meq sodium per day diets, each for 5 days, in a randomized crossover trial. Carotid baroreceptor reflex function was assessed by measuring the blood pressure response to sequential neck suction (0, -10, -20, and -30 mm Hg) and neck pressure (0, +10, +20, and +30 mm Hg). Forearm vascular resistance was determined by venous occlusion plethysmography. Arterial compliance was evaluated by calculating the quotient of the diastolic blood pressure decay time constant and forearm vascular resistance. Blood pressure averaged 124 +/- 3/62 +/- 2 mm Hg on the low sodium diet and 122 +/- 3/60 +/- 2 mm Hg on the high sodium diet (p = NS). Baroreceptor reflex slopes representing the systolic and diastolic blood pressure responses to changes in neck chamber pressure were steeper in the subjects when randomly assigned to low sodium diet than to high sodium diet. Diastolic blood pressure decay time and forearm arterial compliance were similar during low and high sodium intake. We conclude that short-term exposure to a high sodium diet depresses carotid baroreceptor reflex function in normotensive humans. This observation cannot be attributed to changes in the arterial compliance.

Peripubertal ontogeny and estrogen stimulation of cholecystokinin and preproenkephalin mRNA in the rat hypothalamus and limbic system.

The neuropeptide cholecystokinin (CCK) is expressed in limbic system and hypothalamic nuclei that form a circuit that regulates the display of the female rodent reproductive behavior, lordosis. CCK mRNA and peptide levels fluctuate across the estrous cycle and have been shown to be modulated by estrogen exposure. The objective of these experiments was to examine the expression of CCK mRNA during postnatal development of this limbic-hypothalamic, lordosis regulating circuit, and to determine the age at which CCK mRNA expression becomes responsive to estrogen stimulation, by using quantitative in situ hybridization histochemistry. CCK mRNA levels were below the level of detectability within the circuit during the postnatal period, but increased during the peripubertal period. Rats were injected with either estradiol benzoate (EB), EB and progesterone, progesterone, or oil, and were killed 48 hours later on postnatal day (PND) 15, 20, and 25. Alternate brain sections were processed for CCK and preproenkephalin (PPE) mRNA in situ hybridization histochemistry. EB treatment induced CCK mRNA expression in the central portion of the medial preoptic nucleus and posterodorsal medial amygdala at PND 20 and 25, respectively. However, EB treatment increased PPE mRNA levels within the nuclei of the circuit at all ages examined. Progesterone had neither an independent nor additive effect on the EB induction of these neuropeptide messages. The estrogenic induction of CCK mRNA appears to be dependent on estrogen sensitive pathways of neurotransmission, or components of second messenger pathways which regulate CCK mRNA expression in the adult limbic-hypothalamic lordosis regulating circuit, which are not functional before PND 18-25.

Detection of Candida precipitins. a comparison of double diffusion and counter immunoelectrophoresis.

The optimum conditions for detection of Candida precipitins by double diffusion and counter immunoelectrophoresis have been established. Counter immunoelectrophoresis was shown to be more sensitive than double diffusion, and its application to routine tests for Candida precipitins to cytoplasmic antigen is recommended.

The role of lymphangiography in designing fields for elective pelvic node irradiation in Hodgkin's disease.

PURPOSE: We attempted to design a standard pelvic nodal treatment field such that all lymph nodes usually visualized on lymphangiogram would be irradiated with optimal midline blocking of normal tissues. METHODS AND MATERIALS: Two standard fields for treatment of pelvic lymph nodes were designed, based on bony landmarks. The standard fields were applied to the anterior-posterior view of 35 pretherapy lymphangiograms, and the fields were then assessed for inclusion of visible lymph nodes. Measurements were done on the lymphangiograms to assess the amount of additional midline blocking that could be added. RESULTS: All visualized nodes were included in 30 patients (86%) using Standard Field I and in 33 patients (94%) using Standard Field II, but visualized nodes plus a 1.5-cm minimum margin were included in only two patients (6%) with Field I and 24 patients (69%) with Field II. The most frequent sites of close margins were the lateral and medial borders adjacent to the external iliac nodes. Based on the lymphangiograms, a mean of 1.6 cm in male patients and 3.1 cm in female patients could be added to the width of the midline blocks. CONCLUSION: Lymphangiography is useful in designing fields for pelvic node irradiation, both to improve coverage of nodes with a 1.5 cm margin and to increase the amount of central shielding of normal tissues.