A dosimetric comparison of flattening filter free and conventional VMAT treatments for some common cancer sites.

The aim of this study was to assess the potential for treating various common cancer sites with flattening filter free (FFF) rather than conventionally flattened (cFF) treatment plans considering both in-field and out-of-field dosimetry. This study seeks to extend previous work by others to the Elekta Agility VMAT treatments commonly used at our clinic. Nine matched pairs of conventional and FFF 6X treatment plans for prostate, head and neck, and brain cancer sites were generated using the Monaco treatment planning system (Elekta AB, Stockholm, Sweden). Absorbed dose distribution statistics for target and healthy tissue volumes reported by the Monaco treatment planning system were compared. One matched pair of plans for each cancer site was experimentally validated by film and ion chamber measurements in an anthropomorphic phantom. Head leakage was measured at various positions in a small water tank and corrections made to the out-of-field dose distributions calculated by the treatment planning system. Out-of-field organ doses and effective whole body doses were calculated according to ICRP103 (Charles in Radiat Prot Dosim 129:500-507, 2008). The in-field target and organ dose statistics for the cFF and FFF plans were comparable whereas the out-of-field organ and whole body effective doses for plans delivered using 6X FFF were generally lower than those delivered with 6X cFF. A modest increase in monitor unit (MU) delivery rates was also observed with the FFF beams. We conclude that treatment plan delivery using FFF rather than cFF beams is feasible and may provide benefits in terms of reduced out-of-field doses and secondary cancer risks for some patients.

Relationships between estimated flame retardant emissions and levels in indoor air and house dust.

A significant number of consumer goods and building materials can act as emission sources of flame retardants (FRs) in the indoor environment. We investigate the relationship between the emission source strength and the levels of 19 brominated flame retardants (BFRs) and seven organophosphate flame retardants (OPFRs) in air and dust collected in 38 indoor microenvironments in Norway. We use modeling methods to back-calculate emission rates from indoor air and dust measurements and identify possible indications of an emission-to-dust pathway. Experimentally based emission estimates provide a satisfactory indication of the relative emission strength of indoor sources. Modeling results indicate an up to two orders of magnitude enhanced emission strength for OPFRs (median emission rates of 0.083 and 0.41 µg h-1 for air-based and dust-based estimates) compared to BFRs (0.52 and 0.37 ng h-1 median emission rates). A consistent emission-to-dust signal, defined as higher dust-based than air-based emission estimates, was identified for four of the seven OPFRs, but only for one of the 19 BFRs. It is concluded, however, that uncertainty in model input parameters could potentially lead to the false identification of an emission-to-dust signal.

Novel handheld magnetometer probe based on magnetic tunnelling junction sensors for intraoperative sentinel lymph node identification.

Using magnetic tunnelling junction sensors, a novel magnetometer probe for the identification of the sentinel lymph node using magnetic tracers was developed. Probe performance was characterised in vitro and validated in a preclinical swine model. Compared to conventional gamma probes, the magnetometer probe showed excellent spatial resolution of 4.0 mm, and the potential to detect as few as 5 µg of magnetic tracer. Due to the high sensitivity of the magnetometer, all first-tier nodes were identified in the preclinical experiments, and there were no instances of false positive or false negative detection. Furthermore, these preliminary data encourage the application of the magnetometer probe for use in more complex lymphatic environments, such as in gastrointestinal cancers, where the sentinel node is often in close proximity to other non-sentinel nodes, and high spatial resolution detection is required.

Simultaneous determination of Rubisco carboxylase and oxygenase kinetic parameters in Triticum aestivum and Zea mays using membrane inlet mass spectrometry.

The lack of complete Rubisco kinetic data for numerous species is partly because of the time consuming nature of the multiple methods needed to assay all of the Rubisco parameters. We have developed a membrane inlet mass spectrometer method that simultaneously determines the rate of Rubisco carboxylation (v(c)) and oxygenation (v(o)), and the CO(2) and O(2) concentrations. Using the collected data, the Michaels-Menten equations for v(c) and v(o) in response to changing CO(2) and O(2) concentrations were simultaneously solved for the CO(2) (K(c)) and O(2) (K(o)) constants, the maximum turnover rates of the enzyme for CO(2) (kcat(CO2)) and O(2) (kcat(O2)) and the specificity for CO(2) relative to O(2) (S(c/o)). In the C(4) species Zea mays K(c) was higher but K(o) was lower compared with the C(3) species Triticum aestivum. The kcat(CO2) was higher and the kcat(O2) lower in Z. mays compared with T. aestivum and S(c/o) was similar in the two species. The V(omax)/V(cmax) was lower in Z. mays and thus did not correlate with changes in S(c/o). In conclusion, this mass spectrometer system provides a means of simultaneously determining the important Rubisco kinetic parameters, K(c), K(o), kcat(CO2,)kcat(O2) and S(c/o) from the same set of assays.

Home-based infusion therapy for patients with Fabry disease.

Fabry disease is an inherited, progressive, life-threatening disease; therefore, lifelong therapy is needed. By replacing the deficient enzyme, disease progression may be delayed or halted, thereby avoiding serious complications. Hospital-based agalsidase therapy is generally perceived as inconvenient and home-based infusion therapy is greatly appreciated by patients, their families and healthcare professionals. Patients can get familiar with infusion therapy in a hospital setting and, if specific requirements are fulfilled, routine nurse-assisted infusion, or self-care, at the patient's home can be organized. A stable patient who tolerates the infusion and a suitable home environment are prerequisites for home therapy. The authors' clinical experiences underscore the safety and practicality of home therapy. In addition to a major positive impact on the patient's quality of life, home infusion therapy may reduce the constraints of hospital resources. This article reviews the collective experiences with agalsidase beta home infusion therapy and outlines how safe, patient-centred homecare can be organized. Home infusion therapy with Fabrazyme should not be withheld from patients considered eligible according to the proposed criteria. Similar approaches to other enzyme therapies are also possible.

The effect of L-alanine therapy in a patient with adult onset glycogen storage disease type II.

Adult-onset glycogen storage disease type II (GSD II) (McKusick 232300) is a progressive disabling myopathy. At present there is no treatment of proven clinical efficacy. Enzyme replacement therapy may in the future provide benefit but it will be costly and is not yet freely available. L-Alanine, a simple and relatively cheap therapy, has been shown to reduce protein degradation in GSD II patients but has not previously been assessed for clinical benefit in a controlled study. In this study L-alanine was assessed in a double blind, placebo-controlled, crossover n = 1 study. Assessments consisted of spirometry, cardiopulmonary exercise testing, quality of life measurements, biochemical markers and assessment by the criterion 4-component model of body composition. Alanine therapy was associated with a 15% gain in total body protein. However, the patient showed no functional improvement and reported feeling worse after treatment. Further controlled studies in a small group may be warranted, but not widespread use of this therapy.

Exercise capacity and biochemical profile during exercise in patients with glycogen storage disease type I.

Glycogen storage disease type I (GSD-I) is an inherited disorder of carbohydrate metabolism. Hepatic glucose-6-phosphatase is deficient, leading to impaired gluconeogenesis and glycogenolysis. Patients prevent fasting hypoglycemia by frequent feeds of low glycemic index foods. Normal muscle does not contain glucose-6-phosphatase, and GSD-I is usually classified as a hepatic glycogenosis. However, clinical experience has suggested that patients have decreased cardiovascular fitness, but this had not been formally investigated. This paper reports the results of maximal treadmill cardiopulmonary exercise testing in adult patients with GSD-I. It documents a major reduction in exercise capacity in these patients and demonstrates biochemical aspects of exercise that are different from those of normal controls. All patients showed a reduction in exercise capacity, but there was a wide range of exercise tolerance. Additional work needs to address whether improved adherence to or intensification of therapy in adulthood will ameliorate exercise intolerance.

Raised HDL cholesterol in Fabry disease: response to enzyme replacement therapy.

Fabry disease patients have increased risk of vascular disease despite cardioprotective increased HDL-cholesterol. Enzyme therapy does not significantly alter the lipid profile in the short term.

A new, low-volume protein substitute for teenagers and adults with phenylketonuria.

Some older patients with phenylketonuria (PKU) fail to consume their protein substitute (with or without vitamin and mineral supplements) in prescribed amounts, which contributes to poor blood phenylalanine control. PKU Express (Vitaflo), is a new low-volume (amino acids 72 g/100 g), low-carbohydrate, phenylalanine-free protein substitute with added vitamins and minerals designed for people with PKU over 8 years of age. In an open intervention study, the aim was to investigate its acceptability and effectiveness in a group of teenagers and adults with PKU. Twenty-three subjects (15 female; 8 male) with PKU, who had a median age of 17 years (range 8-37 years) took the substitute for 8 weeks. A 3-day prospective diet diary, height, weight, plasma amino acids, biochemical and haematological nutritional analytes were measured at weeks 0 and 8. Skin-puncture bloods for plasma phenylalanine were collected every 2 weeks. The median weight of protein substitute (with or without vitamin and mineral supplements) consumed decreased by 33% from 150 g (range 140-180) daily to 100 g (range 100-125) daily ( p <0.001). Median change in energy intake decreased by a median of 10% (95% CI 2.0 to 18.0) when compared to intake on original protein substitute. On PKU Express, the intakes of all nutrients exceeded the dietary reference values but none was excessively high. Blood phenylalanine decreased by a mean of 37 micromol/L (95% CI-27 to 102) during the trial. Body mass index decreased in 40% of subjects. Changes in blood phenylalanine or body mass index were not statistically significant. Most of the nutritional, haematological and biochemical indices stayed within normal reference ranges for the analytes studied. Sixteen (70%) of the subjects had low plasma selenium at the start, but only 13 (57%) at the study end. Plasma vitamin B12 was high in 8 subjects at the start of the study and 9 at the end. Twenty-one subjects (96%) stated that the product was convenient and easy to prepare. However, 7 (32%) described the smell and 9 (46%) the texture as the same as or worse than those of previous protein substitutes. Because of the use of the premeasured sachets, some subjects were able to prepare their own protein substitute for the first time. PKU Express is a safe, efficacious, protein substitute that significantly reduces the daily volume of prescribed protein substitute.

Development of C4 photosynthesis in sorghum leaves grown under free-air CO2 enrichment (FACE).

The developmental pattern of C4 expression has been well characterized in maize and other C4 plants. However, few reports have explored the possibility that the development of this pathway may be sensitive to changes in atmospheric CO2 concentrations. Therefore, both the structural and biochemical development of leaf tissue in the fifth leaf of Sorghum bicolor plants grown at elevated CO2 have been characterized. Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) and phosphoenolpyruvate carboxylase (PEPC) activities accumulate rapidly as the leaf tissue differentiates and emerges from the surrounding whorl. Rubisco was not expressed in a cell-specific manner in the youngest tissue at the base of the leaf, but did accumulate before PEPC was detected. This suggests that the youngest leaf tissue utilizes a C3-like pathway for carbon fixation. However, this tissue was in a region of the leaf receiving very low light and so significant rates of photosynthesis were not likely. Older leaf tissue that had emerged from the surrounding whorl into full sunlight showed the normal C4 syndrome. Elevated CO2 had no effect on the cell-specific localization of Rubisco or PEPC at any stage of leaf development, and the relative ratios of Rubisco to PEPC remained constant during leaf development. However, in the oldest tissue at the tip of the leaf, the total activities of Rubisco and PEPC were decreased under elevated CO2 implying that C4 photosynthetic tissue may acclimate to growth under elevated CO2.

Adaptive design, female mate preferences, and shifts across the menstrual cycle.

This paper has two aims: first, to review work addressing the functional significance of variation in sexuality across the women's menstrual cycle and its implications for an understanding of human sexual nature; second, to illustrate the more general use of adaptationism in sex research. Adaptationism provides a method for recognizing adaptations, traits that evolved because they bestowed reproductive advantages upon their owners. The telltale sign of adaptation is its special design for a particular function. In recent years, evolutionary psychologists have explored changes in women's sexuality and standards of male attractiveness across the menstrual cycle. Evidence provisionally supports the idea that these changes constitute special design for the function of obtaining genetic benefits through mating with men other than primary partners.

Establishing a collaborative psychopharmacology practice: practical considerations.

Prescriptive authority for the advanced practice psychiatric nurse (APPN) is accompanied by the following advantages: expanded treatment repertoire, increased marketability due to the practicality of having one provider for psychotherapy and pharmacotherapy, and increased collaboration with colleagues. The disadvantages associated with prescriptive authority include: increased professional responsibility and associated liability, labor intensity due to continuing educational demands, medical record documentation, and time-consuming dialogues with referring clinicians. A preexisting relationship between the APPN and the psychiatrist that is based on mutual respect and similarities in treatment philosophies and ethical issues positively influence outcomes.

On the Nusselt number in heat transfer between multiple parallel blood vessels.

Arrays of two or more parallel blood vessels in a tissue matrix have been studied extensively in the context of bioheat transfer. The average vessel Nusselt number (based on the difference between the mixed-mean blood temperature and the average vessel surface temperature) is a crucial parameter in such studies. Various workers have noted tht in particular cases the average Nusselt number is identical to that for fully developed flow in a single vessel in an infinite medium. In other words, the Nusselt number is unaffected by the presence of other vessels. It is proven here that this surprising result holds true for arbitrary number, size, flow direction, and velocity profile in the blood vessels, and for very general boundary conditions on the outer tissue boundary. A useful corollary is that the average wall temperature in a particular vessel may be found by evaluating the temperature fields due to the other vessels and the tissue boundaries at a single point, the center of the vessels in question.

Opiate-induced respiratory depression in pediatric patients.

OBJECTIVE: To describe 15 pediatric patients with opiate-induced respiratory depression. DESIGN: In-house adverse drug reaction (ADR) report forms were reviewed to identify any patients with suspected opiate-induced respiratory depression. Case review was then performed. SETTING: Large pediatric teaching hospital with regional specialties. PATIENTS: Fifteen patients aged 2 days to 17 years (median 14 mo). MAIN OUTCOME MEASURES: Respiratory depression resulting in apnea, hypoxia, cyanosis, reduced respiratory rate, or the need for naloxone following or during opiate administration was recorded. RESULTS: Fifteen patients experienced some degree of respiratory depression over the 3 years of surveillance. Treatment included naloxone (12 patients), admission to the pediatric intensive care unit (8), ventilation (5), and reduction in dosage (1). Predisposing factors for respiratory depression included an age of less than 1 year, excessive dosage, concurrent medical problems, concurrent drugs, and medication errors. CONCLUSIONS: Opiate-induced respiratory depression in pediatric patients occurs infrequently, but may have serious consequences. Opiates are potent analgesics that children require and should receive. Safe use of opiates in pediatric patients, however, depends on the dosage, route and method of administration, consideration of any predisposing factors, and adequate monitoring. This article highlights some of the problems with opiate use in children and gives some recommendations on how these problems may be prevented.

Plasma homocyst(e)ine, folate, and vitamin B-12 concentrations and risk for early-onset coronary artery disease.

High plasma homocyst(e)ine (Hcy) concentrations may be a determinant of coronary artery disease (CAD). Folate and vitamin B-12 are required for the primary metabolic pathway to reduce Hcy concentrations. The interrelationships of Hcy and these two vitamin cofactors were investigated in a case-control study of 101 white males aged 30-50 y with angiographically demonstrated CAD, and 108 white male, similarly aged, control subjects living in the same community as the patients. The odds ratio (OR) of CAD per quartile increase of plasma Hcy concentration based on control values was 1.6 (95% CI: 1.3, 2.1). After age, HDL and LDL cholesterol, body mass index, smoking, hypertension, and diabetes were controlled for, Hcy remained an independent risk factor (OR: 1.4; 95% CI: 1.0, 2.0). The OR change per quartile increase of folate concentration was 0.8 (95% CI: 0.6, 1.0). This difference was reduced (OR: 0.9; 95% CI: 0.7, 1.2) after Hcy adjustment. No difference in the geometric mean of vitamin B-12 concentration was found between patients and control subjects, both 5.8 nmol/L. However, after Hcy and the other CAD risk factors were controlled for, the OR per quartile increase in vitamin B-12 concentration was 1.5 (95% CI: 1.0, 1.8). Reduction in plasma Hcy by interventions to increase plasma folate concentration may decrease CAD risk.

Scalable aspheric corrective mirror for end-pumped solid-state lasers.

A procedure is presented to design an aspheric corrective mirror to remove the effects of thermally induced optical aberrations in end-pumped solid-state lasers. The design is based on solving the inverse problem of bending a thin plate of variable thickness; i.e., given the plate deflection profile a thickness profile must be calculated by solving the differential equation for bending. The advantage of this type of aberration correction is the fact that it can be scaled to different pump powers during operation while still matching the aspheric profile in question. Guidelines for fabrication of the mirror are also presented.

Application of the impedance formalism to diffraction gratings with multiple coating layers.

The standard method of matching boundary conditions at the interfaces of a multilayer plane dielectric stack is shown to be numerically unstable for the evanescent orders when a large number of layers is present. For an isolated dielectric stack with an incident propagating beam there is no need to calculate the evanescent orders; however, when a diffraction grating is buried under the stack there is mixing of orders, and it may be important to calculate the evanescent as well as the propagating orders. It is shown that the impedance formalism removes the numerical instability completely. This method may be coupled to either boundary integral or differential equation methods for the grating to provide the complete solution for the grating-stack system.

Proteinase (Cathepsin B, D, L and Calpains) levels and conditioning rates in normal, electrically stimulated and high-ultimate-pH chicken muscle.

Control, electrically stimulated (ES) and glycogen-depleted (GD) chicken muscles were conditioned at 15°C with continuous mechanical testing for extensibility. The ES and GD muscles went into rigor 3·6 and 2·8 h earlier, respectively, than control muscle. At 24h post-rigor the extensibility of control muscle (11·2%) was markedly less than ES (19·2%) and GD (27·3%) muscles indicating that these latter two treatments should provide more tender meat. Measurement of sarcomere lengths showed no significant differences between control and GD muscle and thus, the greater extensibility in the high pH condition may be restricted to a wider separation of myofibriller fragments at the intermittent fracture zones when under load. Examination of muscle proteinase (cathepsins B, D and L, calpains I and II) and glycosidase (ß-d-glucuronidase, N-acetyl-ß-d-glucosaminidase) levels at 0 and 48h post-slaughter revealed changes in some key enzymes between the different treatments. Calpain I activity declined markedly during 48h storage of ES muscle (83%) compared to control (58%) and GD (63%) muscles. Cathepsin B and L activities did not decline during storage of ES muscle but there was a slight fall in control and GD muscles. Dosing of chicken shortly before slaughter with inhibitors of cysteine proteinases had a negligible effect on conditioning rate, apparently due to lack of inhibition of these proteinases during this short time period in the intact muscle.