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Northwest Medical Physics Center (NMPC) is a nonprofit organization that provides clinical physics support to over 35 radiation therapy facilities concentrated in the Pacific Northwest. Although clinical service is the primary function of NMPC, the diverse array of clinical sites and physics expertise has allowed for the establishment of structured education and research programs, which are complementary to the organization's clinical mission. Three clinical training programs have been developed at NMPC: a therapy medical physics residency program accredited by the Commission on Accreditation of Medical Physics Education Programs (CAMPEP), an Applied Physics Technologist (APT) program, and a summer undergraduate internship program. A partnership has also been established with a major radiation oncology clinical vendor for the purposes of validating and testing new clinical devices across multiple facilities. These programs are managed by a dedicated education and research team at NMPC, made up of four qualified medical physicists (QMPs). The education and research work has made a significant contribution to the organization's clinical mission, and it has provided new training opportunities for early-career physicists across many different clinical environments. Education and research can be incorporated into nonacademic clinical environments, improving the quality of patient care, and increasing the number and type of training opportunities available for medical physicists.

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An anthropomorphic phantom has been developed by Varian Medical Systems for commissioning multileaf-collimator (MLC), stereotactic radiosurgery (SRS) treatments on Varian TrueBeam and Edge linear accelerators. Northwest Medical Physics Center (NMPC) has collected end-to-end data on these machines, at six independent clinical sites, to establish baseline dosimetric and geometric commissioning criteria for SRS measurements with this phantom. The Varian phantom is designed to accommodate four interchangeable target cassettes, each designed for a specific quality assurance function. End-to-end measurements utilized the phantom to verify the coincidence of treatment isocenter with a hidden target in a Winston-Lutz cassette after localization using cone-beam computed tomography (CBCT). Dose delivery to single target (2 cm) and single-isocenter, multitarget (2 and 1 cm) geometries was verified using ionization chamber and EBT3 film cassettes. A nominal dose of 16 Gy was prescribed for each plan using a site's standard beam geometry for SRS cases. Measurements were performed with three Millennium and three high-definition MLC machines at beam energies of 6-MV and 10-MV flattening-filter-free energies. Each clinical site followed a standardized procedure for phantom simulation, treatment planning, quality assurance, and treatment delivery. All treatment planning and delivery was performed using ARIA oncology information system and Eclipse treatment planning software. The isocenter measurements and irradiated film were analyzed using DoseLab quality assurance software; gamma criteria of 3%/1 mm, 3%/0.5 mm, and 2%/1 mm were applied for film analysis. Based on the data acquired in this work, the recommended commissioning criteria for end-to-end SRS measurements with the Varian phantom are as follows: coincidence of treatment isocenter and CBCT-aligned hidden target < 1 mm, agreement of measured chamber dose with calculated dose ≤ 5%, and film gamma passing > 90% for gamma criteria of 3%/1 mm after DoseLab auto-registration shifts ≤ 1 mm in any direction.

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A multileaf collimator (MLC), virtual-cone treatment technique has been commissioned for trigeminal neuralgia (TGN) at Tri-Cities Cancer Center (TCCC). This novel technique was initially developed at the University of Alabama in Birmingham (UAB); it is designed to produce a spherical dose profile similar to a fixed, 5-mm conical collimator distribution. Treatment is delivered with a 10-MV flattening-filter-free (FFF) beam using a high-definition MLC on a Varian Edge linear accelerator. Absolute dose output and profile measurements were performed in a 20 × 20 × 14 cm3 solid-water phantom using an Exradin W2 scintillation detector and Gafchromic EBT3 film. Dose output constancy for the virtual cone was evaluated over 6 months using an Exradin A11 parallel plate chamber. The photo-neutron dose generated by these treatments was assessed at distances of 50 and 100 cm from isocenter using a Ludlum Model 30-7 Series Neutron Meter. TGN treatments at TCCC have been previously delivered at 6-MV FFF using a 5-mm stereotactic cone. To assess the dosimetric impact of using a virtual cone, eight patients previously treated for TGN with a 5-mm cone were re-planned using a virtual cone. Seven patients have now been treated for TGN using a virtual cone at TCCC. Patient-specific quality assurance was performed for each patient using Gafchromic EBT-XD film inside a Standard Imaging Stereotactic Dose Verification Phantom. The commissioning results demonstrate that the virtual-cone dosimetry, first described at UAB, is reproducible on a second Edge linear accelerator at an independent clinical site. The virtual cone is a credible alternative to a physical, stereotactic cone for the treatment of TGN at TCCC.

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In the version of this article initially published, in Fig. 5a, the data in the right column of 'DAAM2 gRNA1' were incorrectly plotted as circles indicating 'untreated' rather than as squares indicating 'treated'. The error has been corrected in the HTML and PDF versions of the article.

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Osteoporosis is a common aging-related disease diagnosed primarily using bone mineral density (BMD). We assessed genetic determinants of BMD as estimated by heel quantitative ultrasound in 426,824 individuals, identifying 518 genome-wide significant loci (301 novel), explaining 20% of its variance. We identified 13 bone fracture loci, all associated with estimated BMD (eBMD), in ~1.2 million individuals. We then identified target genes enriched for genes known to influence bone density and strength (maximum odds ratio (OR) = 58, P = 1 × 10-75) from cell-specific features, including chromatin conformation and accessible chromatin sites. We next performed rapid-throughput skeletal phenotyping of 126 knockout mice with disruptions in predicted target genes and found an increased abnormal skeletal phenotype frequency compared to 526 unselected lines (P < 0.0001). In-depth analysis of one gene, DAAM2, showed a disproportionate decrease in bone strength relative to mineralization. This genetic atlas provides evidence linking associated SNPs to causal genes, offers new insight into osteoporosis pathophysiology, and highlights opportunities for drug development.

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OBJECTIVES: Anterior cervical discectomy and fusion (ACDF) is a common operative treatment of compressive pathology of the cervical spinal cord, when caused by one or more degenerated intervertebral discs or related osteophytes. In addition to intra-operative radiographs to confirm spinal level before discectomy and implant position after insertion, traditional practice is to obtain post-operative antero-posterior and lateral plain radiographs (XR) before hospital discharge, despite a paucity of evidence supporting their benefit to patient care. Minimising unnecessary radiation to radiosensitive neck structures is desirable, and furthermore, with increasing financial pressure on healthcare resources, routine investigations should be clinically justified and evidence-based. We aim to compare the utility of routine post-operative cervical spine X-rays following ACDF. METHODS: We compare two groups of consecutive patients undergoing ACDF in a single UK neurosurgical centre. The first group (n = 109) received routine post-operative XR imaging, and the second group (n = 113) received radiographs only when clinically indicated. RESULTS: There were no differences in post-operative complication rates (4.6% vs. 5.3%), or requirement for further imaging or of further operative intervention (1.8% vs. 0.9%). The group that did not have routine post-operative radiographs had a significantly shorter stay in hospital (median two days vs. three days). There were no patients in either group where post-operative XR changed clinical management and mandated revision surgery or further imaging. All cases requiring surgery or further imaging were identified by clinical deterioration. CONCLUSIONS: We suggest that the practice of obtaining routine radiographs of the cervical spine following ACDF should be abandoned, unless there is a clear clinical indication.

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Fifteen primiparous crossbred dairy cows that were 114±14d in milk and weighed 533±56kg were used in a replicated 5×5 Latin square to test the efficacy of a calcium montmorillonite clay, NovaSil Plus (NSP; BASF Corp., Ludwigshaven, Germany), for the reduction of aflatoxin (AF) metabolite (AFM1) in milk and the effect of NSP on milk composition. Cows were housed in a freestall barn, fed once a day and milked twice a day. The experiment consisted of five 14-d periods: d 1 through 7 were considered for data collection, and d 8 through 14 were considered a wash-out phase. In each period, cows were randomly assigned to 1 of 5 dietary treatments: (1) control (CON), consisting of a basal total mixed ration (TMR); (2) high-dose NSP diet (NSP-1%), consisting of TMR plus 230 g of NSP; (3) aflatoxin diet (AFD), consisting of the TMR plus AF challenge; (4) low-dose NSP with AF (NSP-0.5%+AFD), composed of TMR plus 115 g of NSP and AF challenge; and (5) high-dose NSP with AF (NSP-1%+AFD), consisting of TMR plus 230 g of NSP and AF challenge. The AF challenge consisted of top dressing a daily dose of 100 µg/kg estimated dry matter intake (DMI); similarly, NSP was fed at 1.0 or 0.5% of estimated DMI. Milk yield and DMI were similar across treatments averaging 21.1±1.33 kg/d and 19.7±0.56 kg/d, respectively. Concentration of milk fat, protein, and lactose were similar across treatments with averages of 4.91±0.20%, 3.85±0.10%, and 4.70±0.06%, respectively. Concentration of vitamin A averaged 0.28±0.03 µg/mL and riboflavin concentration averaged 1.57±0.13 µg/mL across treatments. The concentration of minerals in milk were similar for all treatments. Cows fed CON and NSP-1% yielded the lowest concentration of AFM1 in milk with 0.03 and 0.01±0.06 µg/L. Addition of NSP reduced milk AFM1 from 1.10±0.06 µg/L with the AF diet to 0.58 and 0.32±0.06 µg/L with the NSP-0.5%+AF and NSP-1%+AF diets, respectively. Excretion of AFM1 was reduced by NSP; mean values were 24.38, 11.86, 7.38, 0.64, and 0.23, ± 1.71 µg/d, for AFD, NSP-0.5%+AFD, NSP-1%+AFD, NSP-1%, and CON, respectively. More specifically, 1.07±0.08% of the daily AF intake was transferred to the milk of cows consuming the AFD, whereas the AF transfer rates in milk from cows that consumed the NSP-0.5%+AFD and NSP-1%+AFD were 0.52 and 0.32±0.08%. Results from this research demonstrate that feeding NSP to lactating cows is an effective method to reduce the transfer and excretion of AFM1 in milk with no negative effects on dry matter intake, milk production, and composition.

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In genetic toxicology, risk assessment has traditionally adopted linear dose-responses for any compound that causes genotoxic effects. Increasing evidence of non-linear dose-responses, however, suggests potential cellular tolerance to low levels of many genotoxicants with diverse modes of action. Such putative non-linear dose-responses need to be substantiated by strong mechanistic data that identifies the mechanisms responsible for the tolerance to low doses. This can be achieved by experimental demonstration of cytoprotective mechanisms and by providing experimental support for the existence of tolerance mechanisms against low dose effects. By highlighting key experiments into low dose mechanisms, this review aims to clarify which mechanistic data are required to support the use of non-linear dose-response models in risk assessment. Such key experiments are presented and discussed for alkylating agents, oxidants, particulate matter, nucleoside analogues, topoisomerase inhibitors and aneugens and exemplify the use of gene knockout models or transgenic models as well as chemical modulators of key effectors of relevant pathways and their impact on dose-response relationships. In vitro studies are particularly valuable to elucidate mechanisms of low-dose protection or lack thereof, while in vivo experiments are most appropriate for deriving a safe dose. In order to evaluate the existence of non-linear dose-response relationships for genotoxicants, we suggest that careful attention should be given to the mode of genotoxic action, relevant biomarkers of exposure, as well as to the existence and impact of potential cytoprotective mechanisms like detoxifying metabolism and DNA repair.

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The goal of the current study was to measure the energy dependence of survival of rat 9L glioma cells labeled with iododeoxyuridine (IUdR) that underwent photon-activated Auger electron therapy using 25-35 keV monochromatic X rays, i.e., above and below the K-edge energy of iodine. Rat 9L glioma cells were selected because of their radioresistance, ability to be implanted for future in vivo studies and analogy to radioresistant human gliomas. Survival curves were measured for a 4 MV X-ray beam and synchrotron produced monochromatic 35, 30 and 25 keV X-ray beams. IUdR was incorporated into the DNA at levels of 0, 9 and 18% thymidine replacement for 4 MV and 35 keV and 0 and 18% thymidine replacement for 30 and 25 keV. For 10 combinations of beam energy and thymidine replacement, 62 data sets (3-13 per combination) provided 776 data points (47-148 per combination). Survival versus dose data taken for the same combination, but on different days, were merged by including the zero-dose points in the nonlinear, chi-squared data fitting using the linear-quadratic model and letting the best estimate to the zero-dose plating efficiency for each of the different days be a fitting parameter. When comparing two survival curves, the ratio of doses resulting in 10% survival gave sensitization enhancement ratios (SER10) from which contributions due to linear energy transfer (LET) (SER10,LET), IUdR radiosensitization (SER10,RS), the Auger effect (SER10,AE) and the total of all effects (SER10,T) were determined. At 4 MV and 35, 30 and 25 keV, SER10,LET values were 1.00, 1.08 ± 0.03, 1.22 ± 0.02 and 1.37 ± 0.02, respectively. At 4 MV SER10,RS values for 9 and 18% IUdR were 1.28 ± 0.02 and 1.40 ± 0.02, respectively. Assuming LET effects were independent of percentage IUdR and radiosensitization effects were independent of energy, SER10,AE values for 18% IUdR at 35, 30 and 25 keV were 1.35 ± 0.05, 1.06 ± 0.03 and 0.98 ± 0.03, respectively. The value for 9% IUdR at 35 keV was 1.01 ± 0.04. First, we found the radioresistant rat 9L glioma cell line exhibited an SER10 due to the Auger effect of 1.35 at (35 keV, 18% IUdR) and an SER10 due to the radiosensitizing effect of 1.40 at (4 MV, 18% IUdR), both significantly less than values for previously reported cell lines. These low individual values emphasize the benefit of their combined value (SER10 of approximately 1.9) for achieving clinical benefit. Second, as expected, we observed that energies below the K-edge of iodine (25 and 30 keV), for which there are L, M and higher shell photoelectric events creating Auger electrons, show no promise for Auger electron therapy. Third, to proceed with future in vivo studies, additional data from 35-65 keV are needed to determine the optimal X-ray energy for IUdR Auger electron therapy. Only then can there be an answer to the question, how well the energy dependence of in vitro survival data supports the potential for photon-activated Auger electron therapy with IUdR in cancer radiotherapy.

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Recent restrictions on the testing of cosmetic ingredients in animals have resulted in the need to test the genotoxic potential of chemicals exclusively in vitro prior to licensing. However, as current in vitro tests produce some misleading positive results, sole reliance on such tests could prevent some chemicals with safe or beneficial exposure levels from being marketed. The 3D human reconstructed skin micronucleus (RSMN) assay is a promising new in vitro approach designed to assess genotoxicity of dermally applied compounds. The assay utilises a highly differentiated in vitro model of the human epidermis. For the first time, we have applied automated micronucleus detection to this assay using MetaSystems Metafer Slide Scanning Platform (Metafer), demonstrating concordance with manual scoring. The RSMN assay's fixation protocol was found to be compatible with the Metafer, providing a considerably shorter alternative to the recommended Metafer protocol. Lowest observed genotoxic effect levels (LOGELs) were observed for mitomycin-C at 4.8 µg/ml and methyl methanesulfonate (MMS) at 1750 µg/ml when applied topically to the skin surface. In-medium dosing with MMS produced a LOGEL of 20 µg/ml, which was very similar to the topical LOGEL when considering the total mass of MMS added. Comparisons between 3D medium and 2D LOGELs resulted in a 7-fold difference in total mass of MMS applied to each system, suggesting a protective function of the 3D microarchitecture. Interestingly, hydrogen peroxide (H2O2), a positive clastogen in 2D systems, tested negative in this assay. A non-genotoxic carcinogen, methyl carbamate, produced negative results, as expected. We also demonstrated expression of the DNA repair protein N-methylpurine-DNA glycosylase in EpiDerm™. Our preliminary validation here demonstrates that the RSMN assay may be a valuable follow-up to the current in vitro test battery, and together with its automation, could contribute to minimising unnecessary in vivo tests by reducing in vitro misleading positives.

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Experts working on behalf of international development organisations need better tools to assist land managers in developing countries maintain their livelihoods, as climate change puts pressure on the ecosystem services that they depend upon. However, current understanding of livelihood vulnerability to climate change is based on a fractured and disparate set of theories and methods. This review therefore combines theoretical insights from sustainable livelihoods analysis with other analytical frameworks (including the ecosystem services framework, diffusion theory, social learning, adaptive management and transitions management) to assess the vulnerability of rural livelihoods to climate change. This integrated analytical framework helps diagnose vulnerability to climate change, whilst identifying and comparing adaptation options that could reduce vulnerability, following four broad steps: i) determine likely level of exposure to climate change, and how climate change might interact with existing stresses and other future drivers of change; ii) determine the sensitivity of stocks of capital assets and flows of ecosystem services to climate change; iii) identify factors influencing decisions to develop and/or adopt different adaptation strategies, based on innovation or the use/substitution of existing assets; and iv) identify and evaluate potential trade-offs between adaptation options. The paper concludes by identifying interdisciplinary research needs for assessing the vulnerability of livelihoods to climate change.

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PURPOSE: This work investigates the dose-response curves of GAFCHROMIC(®) EBT, EBT2, and EBT3 radiochromic films using synchrotron-produced monochromatic x-ray beams. EBT2 film is being utilized for dose verification in photoactivated Auger electron therapy at the Louisiana State University Center for Advanced Microstructures and Devices (CAMD) synchrotron facility. METHODS: Monochromatic beams of 25, 30, and 35 keV were generated on the tomography beamline at CAMD. Ion chamber depth-dose measurements were used to determine the dose delivered to films irradiated at depths from 0.7 to 8.5 cm in a 10 × 10 × 10-cm(3) polymethylmethacrylate phantom. AAPM TG-61 protocol was applied to convert measured ionization into dose. Films were digitized using an Epson 1680 Professional flatbed scanner and analyzed using the net optical density (NOD) derived from the red channel. A dose-response curve was obtained at 35 keV for EBT film, and at 25, 30, and 35 keV for EBT2 and EBT3 films. Calibrations of films for 4 MV x-rays were obtained for comparison using a radiotherapy accelerator at Mary Bird Perkins Cancer Center. RESULTS: The sensitivity (NOD per unit dose) of EBT film at 35 keV relative to that for 4-MV x-rays was 0.73 and 0.76 for doses 50 and 100 cGy, respectively. The sensitivity of EBT2 film at 25, 30, and 35 keV relative to that for 4-MV x-rays varied from 1.09-1.07, 1.23-1.17, and 1.27-1.19 for doses 50-200 cGy, respectively. For EBT3 film the relative sensitivity was within 3% of unity for all three monochromatic x-ray beams. CONCLUSIONS: EBT and EBT2 film sensitivity showed strong energy dependence over an energy range of 25 keV-4 MV, although this dependence becomes weaker for larger doses. EBT3 film shows weak energy dependence, indicating that it would be a better dosimeter for kV x-ray beams where beam hardening effects can result in large changes in the effective energy.

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PURPOSE: Ion chamber dosimetry is being used to calibrate dose for cell irradiations designed to investigate photoactivated Auger electron therapy at the Louisiana State University Center for Advanced Microstructures and Devices (CAMD) synchrotron facility. This study performed a dosimetry intercomparison for synchrotron-produced monochromatic x-ray beams at 25 and 35 keV. Ion chamber depth-dose measurements in a polymethylmethacrylate (PMMA) phantom were compared with the product of MCNP5 Monte Carlo calculations of dose per fluence and measured incident fluence. METHODS: Monochromatic beams of 25 and 35 keV were generated on the tomography beamline at CAMD. A cylindrical, air-equivalent ion chamber was used to measure the ionization created in a 10 × 10 × 10-cm(3) PMMA phantom for depths from 0.6 to 7.7 cm. The American Association of Physicists in Medicine TG-61 protocol was applied to convert measured ionization into dose. Photon fluence was determined using a NaI detector to make scattering measurements of the beam from a thin polyethylene target at angles 30°-60°. Differential Compton and Rayleigh scattering cross sections obtained from xraylib, an ANSI C library for x-ray-matter interactions, were applied to derive the incident fluence. MCNP5 simulations of the irradiation geometry provided the dose deposition per photon fluence as a function of depth in the phantom. RESULTS: At 25 keV the fluence-normalized MCNP5 dose overestimated the ion-chamber measured dose by an average of 7.2 ± 3.0%-2.1 ± 3.0% for PMMA depths from 0.6 to 7.7 cm, respectively. At 35 keV the fluence-normalized MCNP5 dose underestimated the ion-chamber measured dose by an average of 1.0 ± 3.4%-2.5 ± 3.4%, respectively. CONCLUSIONS: These results showed that TG-61 ion chamber dosimetry, used to calibrate dose output for cell irradiations, agreed with fluence-normalized MCNP5 calculations to within approximately 7% and 3% at 25 and 35 keV, respectively.

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Inherited deficiency of the seventh complement component (C7) is associated with increased susceptibility to Neisseria meningitidis infections. The disease is rare in most Western countries. Here we report new investigations of a large, but incompletely characterized genomic deletion of exons 8 and 9 [c.739-?_1093+?del], previously identified in three unrelated Irish families with C7 deficiency. We have analysed DNA from one individual, who is homozygous for the deletion, by PCR using primers progressively proximal to the deleted exons. Thus we were able to map the deletion boundaries. Amplification across the breakpoint and sequencing revealed an indel mutation that included a 6.4kb deletion together with an insertion of a novel 8bp sequence [c.739+1262_1270-2387delinsGCAGGCCA]. We demonstrated the same defect in the C7 deficient patients from each family and developed a duplex PCR method to enable the detection of alleles containing the deletion in heterozygotes. A member of a fourth family was found to be homozygous for the deletion defect. Thus, the deletion defect may be a more commonly distributed cause of C7 deficiency in Ireland.

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OBJECTIVE: We report a unique complication arising from the use of a Hunsaker Mon-Jet ventilation tube during microlaryngeal surgery, and we briefly review the literature on the use of this tube for jet ventilation. METHOD: A case report on the safe and successful management of a potential airway compromise, and a brief literature review on using the Hunsaker Mon-Jet ventilation tube during microlaryngeal surgery. CASE REPORT: A 46-year-old woman was scheduled to undergo removal of a vocal cord polyp under general anaesthesia. However, the polyp became stuck in the basket of the Hunsaker tube during intubation. The polyp and the Hunsaker tube were removed safely after a microlaryngeal tube was passed beyond the vocal cords. To our knowledge, this complication has not previously been reported. CONCLUSION: This case highlights the potential risk of laryngeal growths, especially vocal cord polyps, becoming trapped in the Hunsaker tube during intubation. Both the anaesthetist and the operating surgeon should be aware of this possible complication and, more importantly, how to deal with such a problem.

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HIV/AIDS prevention strategies often neglect traditions and cultural practices relevant to the spread of HIV. The role of women in the HIV/AIDS context has typically been relegated to high-risk female groups such as sex workers, or those engaged in transactional sex for survival. Consequently, these perceptions are born out in the escalation of HIV/AIDS among communities, and female populations in particular where prevention frameworks remain culturally intolerant. We have attempted to address these issues by using an adapted Rapid Assessment Response and Evaluation (RARE) model to examine the impact of HIV/AIDS in the Maasai community of Ngorongoro. Our adapted RARE model used community engagement venues such as stockholder workshops, key informant interviews, and focus groups. Direct observations and geomapping were also done. Throughout our analysis, a gender and a pastoralist-centered approach provided methodological guidance, and served as value added contributions to out adaptation. Based in the unique context of a rural pastoralist community, we made recommendations appropriate to the cultural setting and the RARE considerations.

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Outcomes after esophagectomy may be related to many factors, including the age of the patient, the stage of the tumor, the operative approach, and the incidence of postoperative morbidity. Pulmonary complications are the major source of morbidity and mortality following esophageal resection, and numerous studies have identified various factors associated with these complications. Preoperative factors affecting pulmonary complications include advanced age, poor nutritional status, and poor cardiopulmonary reserve, whereas preoperative chemoradiation therapy is not clearly associated with increased pulmonary complications. Intraoperative factors associated with increased rates of pulmonary complications include increased blood loss, prolonged operative times, advanced or proximal esophageal tumors, and more extensive operations, including the McKeown resection with three-field lymph node dissection. Postoperative factors associated with pulmonary complications include the development of atrial fibrillation, recurrent laryngeal nerve injury, and aspiration or other abnormality of deglutition. Potential maneuvers to limit the severity of pulmonary complications include smoking cessation prior to surgery, aggressive pulmonary toilet, and documentation of intact swallowing mechanisms prior to the resumption of oral intake after surgery.

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The objective of this study was to examine the interplay between osmotic and oxidative stress as well as to determine mechanisms by which osmotic stress increases superoxide generation in spermatozoa of horses. Superoxide production, as measured by dihydroethidium (DHE), increased when spermatozoa of horses were incubated under either hyperosmotic or hyposmotic conditions. This increase in superoxide production was inhibited by the MAP kinase p38 inhibitor, SB203580, and by the superoxide scavenger, tiron. Incubation of spermatozoa under hyperosmotic conditions increased overall protein tyrosine phosphorylation as measured by western blotting techniques; however, a similar increase was not detected when spermatozoa were incubated under hyposmotic conditions. The general protein kinase C (PKC) and protein tyrosine kinase (PTK) inhibitor staurosporine inhibited (P<0.05) tyrosine phosphorylation in samples from cells under hyperosmotic conditions. In addition, the NADPH oxidase inhibitor diphenyleneiodonium (DPI) also inhibited (P<0.05) protein tyrosine phosphorylation in cells under hyperosmotic conditions. In summary, these data indicate that incubation of equine spermatozoa under both hyposmotic and hyperosmotic conditions can increase superoxide anion generation. Under hyperosmotic conditions, this increased generation of superoxide anion was accompanied by increased protein tyrosine phosphorylation.

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Reaction of an ethylenediamine solution of the intermetallic Zintl phase K4Pb9 with dimesitylcadmium yielded the dimeric Zintl ion [Pb9Cd-CdPb9]6- in low crystalline yield. The cluster anion exhibits a Cd-Cd bond and was structurally characterised by single crystal X-ray diffraction in [K(2,2,2-crypt)]6[Cd2Pb18].2en (1). DFT was also used to explore the bonding in the hexa-anionic cluster.

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A recently improved understanding of gut immunity has merged with current thinking in biological and medical science, pointing to an apparent function of the mammalian cecal appendix as a safe-house for symbiotic gut microbes, preserving the flora during times of gastrointestinal infection in societies without modern medicine. This function is potentially a selective force for the evolution and maintenance of the appendix, and provides an impetus for reassessment of the evolution of the appendix. A comparative anatomical approach reveals three apparent morphotypes of the cecal appendix, as well as appendix-like structures in some species that lack a true cecal appendix. Cladistic analyses indicate that the appendix has evolved independently at least twice (at least once in diprotodont marsupials and at least once in Euarchontoglires), shows a highly significant (P < 0.0001) phylogenetic signal in its distribution, and has been maintained in mammalian evolution for 80 million years or longer.

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