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Introduction: The aim was to determine which immobilisation device improved inter-fraction reproducibly of pelvic tilt and required the least pre-treatment setup and planning interventions., Methods: Sixteen patients were retrospectively reviewed, eight immobilised using the BodyFIX system (BodyFIX®, Elekta, Stockholm, Sweden) and eight using the Butterfly Board (BB) (Bionix Radiation Therapy, Toledo, OH, USA). The daily pre-treatment images were reviewed to assess setup variations between each patient and groups for pelvic tilt, pubic symphysis, sacral promontory and the fifth lumbar spine (L5)., Results: Compared with the planning CT, pelvic tilt for most patients was within ±2° using the BodyFIX and ± 4° for the BB. The Butterfly Board had a slightly higher variance both for patient-to-patient (standard deviation of the systematic error) and day-to-day error (standard deviation of the random error). Variance in position between individual patients and the two stabilisation devices were minimal in the anterior-posterior (AP) and superior-inferior (SI) direction for the pubic symphysis, sacral promontory and L5 spine. Re-imaged fractions due to pelvic tilt reduced by about half when BodyFIX was used (39.1% BB, 19.4% BodyFIX). One patient treated with the BB required a re-scan for pelvic tilt. Three patients required a re-scan for body contour variations (two using BodyFIX and one with the BB)., Conclusions: BodyFIX resulted in a more accurate inter-fraction setup and efficient treatment and is used as the standard stabilisation for gynaecological patients at our centre. It reduced the pelvic tilt variance and reduced the need for re-imaging pre-treatment by half., (© 2024 The Author(s). Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.)

Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental condition characterized by developmentally extreme and impairing symptoms of inattention and/or hyperactivity/impulsivity. Great interest has emerged in the ways ADHD and its underlying symptom dimensions relate to the development of personality traits. Much extant research on this topic is cross-sectional, relying on self-report measures and male samples. Herein, we present data from a prospective, longitudinal study of a socioeconomically and racially diverse sample of girls, including those with ADHD and a matched neurotypical comparison sample. We examined how parent- and teacher-reported ADHD in middle childhood relate to self-reported Big Five personality traits in adolescence. As expected, childhood ADHD diagnosis prospectively predicted lower self-reported Conscientiousness, lower Agreeableness, and higher Neuroticism in adolescence. With ADHD diagnosis covaried, Inattention (IA) predicted only low Conscientiousness, Hyperactivity/Impulsivity (HI) predicted only low Agreeableness, and neither predicted adolescent Neuroticism. An exploratory moderator analysis showed that family income moderated the effects of IA and HI on the negativity of adolescent self-descriptions of their own personalities, with more pronounced negative effects for girls in families with higher (rather than lower) income. Familial pressures to achieve in higher-income families may be linked to more pronounced negative ramifications of ADHD on personality development., (© 2024. The Author(s).)

Using multipathogen PCR testing, we identified 195 students with adenovirus type 4 infections on a university campus in South Carolina, USA, during January-May 2022. We co-detected other respiratory viruses in 43 (22%) students. Continued surveillance of circulating viruses is needed to prevent virus infection outbreaks in congregate communities.

Introduction: Aimed to develop a simple and robust volumetric modulated arc radiotherapy (VMAT) solution for comprehensive lymph node (CLN) breast cancer without increase in low-dose wash., Methods: Forty CLN-breast patient data sets were utilised to develop a knowledge-based planning (KBP) VMAT model, which limits low-dose wash using iterative learning and base-tangential methods as benchmark. Another twenty data sets were employed to validate the model comparing KBP-generated ipsilateral VMAT (ipsi-VMAT) plans against the benchmarked hybrid (h)-VMAT (departmental standard) and bowtie-VMAT (published best practice) methods. Planning target volume (PTV), conformity/homogeneity index (CI/HI), organ-at-risk (OAR), remaining-volume-at-risk (RVR) and blinded radiation oncologist (RO) plan preference were evaluated., Results: Ipsi- and bowtie-VMAT plans were dosimetrically equivalent, achieving greater nodal target coverage (P < 0.05) compared to h-VMAT with minor reduction in breast coverage. CI was enhanced for a small reduction in breast HI with improved dose sparing to ipsilateral-lung and humeral head (P < 0.05) at immaterial expense to spinal cord. Significantly, low-dose wash to OARs and RVR were comparable between all plan types demonstrating a simple VMAT class solution robust to patient-specific anatomic variation can be applied to CLN breast without need for complex beam modification (hybrid plans, avoidance sectors or other). This result was supported by blinded RO review., Conclusions: A simple and robust ipsilateral VMAT class solution for CLN breast generated using iterative KBP modelling can achieve clinically acceptable target coverage and OAR sparing without unwanted increase in low-dose wash associated with increased second malignancy risk., (© 2021 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.)

Objective : We evaluated trajectories of attention-deficit/hyperactivity (ADHD)-relevant behaviors in a sample of infants at high and low familial risk for ADHD who were prospectively evaluated at 12, 18, and 24 months of age. Method : Participants included 43 infants at risk for ADHD based on family history (i.e., diagnosed first-degree relative) and 40 low-risk infants (i.e., no family history of ADHD). Instances of inattention, out-of-seat, and grabbing behavior were coded from video; analogous constructs were rated by examiners unaware of familial risk status after completing structured standardized assessments with the infants/toddlers. At the end of each study visit, examiners solicited parents' concerns about their child's behavior. Differences in ADHD-related behaviors and parent concerns were examined between 12 and 24 months of age. Results : Infants with an older sibling or parent diagnosed with ADHD were distinguishable from infants with no family history of ADHD as early as 12 months of age based on directly observed and examiner reports of behavior, particularly with respect to hyperactive-impulsive behavior. Parents of infants at familial risk for ADHD also reported significantly more behavior/temperament concerns as early as 12 months of age compared to parents of infants at low risk for ADHD. Conclusions : These findings highlight the ability to detect genetic liability for ADHD by the end of the first year of life, suggesting that well-designed family risk studies of ADHD are feasible and may be clinically valuable. They also suggest the potential for earlier detection of risk for ADHD than has previously been possible.

Nicotinamide-adenine dinucleotide (NAD) is involved in redox homeostasis and acts as a substrate for NADases, including poly(ADP-ribose) polymerases (PARPs) that add poly(ADP-ribose) polymers to proteins and DNA, and sirtuins that deacetylate proteins. Nicotinamide, a by-product of NADases increases circadian period in both plants and animals. In mammals, the effect of nicotinamide on circadian period might be mediated by the PARPs and sirtuins because they directly bind to core circadian oscillator genes. We have investigated whether PARPs and sirtuins contribute to the regulation of the circadian oscillator in Arabidopsis. We found no evidence that PARPs and sirtuins regulate the circadian oscillator of Arabidopsis or are involved in the response to nicotinamide. RNA-seq analysis indicated that PARPs regulate the expression of only a few genes, including FLOWERING LOCUS C. However, we found profound effects of reduced sirtuin 1 expression on gene expression during the day but not at night, and an embryo lethal phenotype in knockouts. Our results demonstrate that PARPs and sirtuins are not associated with NAD regulation of the circadian oscillator and that sirtuin 1 is associated with daytime regulation of gene expression., (© 2021 The Authors. Plant, Cell & Environment published by John Wiley & Sons Ltd.)

Background: To measure intra-fraction displacement (IFD) in post-prostatectomy patients treated with anisotropic margins and daily soft tissue matching., Methods: Pre-treatment cone beam computed tomography (CBCT) scans were acquired daily and post-treatment CBCTs for the first week then weekly on 46 patients. The displacement between the scans was calculated retrospectively to measure IFD of the prostate bed (PB). The marginal miss (MM) rate, and the effect of time between imaging was assessed., Results: A total of 392 post-treatment CBCT's were reviewed from 46 patients. The absolute mean (95% CI) IFD was 1.5 mm (1.3-1.7 mm) in the AP direction, 1.0 mm (0.9-1.2 mm) SI, 0.8 mm (0.7-0.9 mm) LR, and 2.4 mm (2.2-2.5 mm) 3D displacement. IFD ≥  ± 3 mm and ≥  ± 5 mm was 24.7% and 5.4% respectively. MM of the PB was detected in 33 of 392 post-treatment CBCT (8.4%) and lymph nodes in 6 of 211 post-treatment CBCT images (2.8%). Causes of MM due to IFD included changes in the bladder (87.9%), rectum (66.7%) and buttock muscles (6%). A time ≥ 9 min between the pre and post-treatment CBCT demonstrated that movement ≥ 3 mm and 5 mm increased from 19.2 to 40.5% and 5 to 8.1% respectively., Conclusions: IFD during PB irradiation was typically small, but was a major contributor to an 8.4% MM rate when using daily soft tissue match and tight anisotropic margins.

Since February 12, 2020, approximately 6.5 million cases of SARS-CoV-2 infection, the cause of coronavirus disease 2019 (COVID-19), and 190,000 SARS-CoV-2-associated deaths have been reported in the United States (1,2). Symptoms associated with SARS-CoV-2 infection are milder in children compared with adults (3). Persons aged <21 years constitute 26% of the U.S. population (4), and this report describes characteristics of U.S. persons in that population who died in association with SARS-CoV-2 infection, as reported by public health jurisdictions. Among 121 SARS-CoV-2-associated deaths reported to CDC among persons aged <21 years in the United States during February 12-July 31, 2020, 63% occurred in males, 10% of decedents were aged <1 year, 20% were aged 1-9 years, 70% were aged 10-20 years, 45% were Hispanic persons, 29% were non-Hispanic Black (Black) persons, and 4% were non-Hispanic American Indian or Alaska Native (AI/AN) persons. Among these 121 decedents, 91 (75%) had an underlying medical condition,* 79 (65%) died after admission to a hospital, and 39 (32%) died at home or in the emergency department (ED). † These data show that nearly three quarters of SARS-CoV-2-associated deaths among infants, children, adolescents, and young adults have occurred in persons aged 10-20 years, with a disproportionate percentage among young adults aged 18-20 years and among Hispanics, Blacks, AI/ANs, and persons with underlying medical conditions. Careful monitoring of SARS-CoV-2 infections, deaths, and other severe outcomes among persons aged <21 years remains particularly important as schools reopen in the United States. Ongoing evaluation of effectiveness of prevention and control strategies will also be important to inform public health guidance for schools and parents and other caregivers., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Introduction: We have previously demonstrated that daily soft tissue matching with reduced anisotropic margins provides an ideal balance between prostate bed coverage and meeting organ at risk constraints. The aim of this study was to evaluate the implementation of this approach in clinical practice., Methods: Thirty-eight radiation therapists (RTs) completed offline IGRT training involving six patients. After training was completed, this approach was implemented clinically. The first 24 patients were evaluated with a central review of match displacements and geographic miss (GM). An assessment of treatment times and planning parameters was also performed., Results: During offline training, the anterior-posterior (AP) match discrepancy had the largest mean variation ranging from -0.46 to 0.06 cm and undetected geographic miss occurred in 17% of alignments. The mean time taken to treat the first 24 patients ranged from 12.2 to 20.6 min. The smaller anisotropic margin resulted in similar target coverage but achieved reduced doses to the bladder (V65Gy from 36% to 27%, V40Gy from 54% to 51%) and rectum (V65Gy from 20% to 19%, V60Gy from 27% to 24%, V40Gy from 42% to 38%). The matches of 806 CBCT images in 24 patients were reviewed. The mean match ranged from -0.12 to 0.17 cm AP, -0.14 to 0.14 cm superior-inferior (SI) and -0.04 to 0.04 cm left-right (LR). An undetected geographic miss was found in the prostate bed in 17 (2.1%) images and lymph nodes in 2 (0.2%) images., Conclusions: Daily soft tissue IGRT with reduced anisotropic margins for post-prostatectomy radiotherapy has been successfully implemented. RTs performed better with real-time online matching than they did in offline training, perhaps influenced by having several RTs perform online matching. Daily soft tissue IGRT did not prolong treatment time., (© 2019 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.)

Background: The 'dysregulation profile' (DP) is a measure of emotional and behavioral dysregulation that may cut across diagnostic boundaries. Siblings of children with autism spectrum disorder (ASD) who do not develop ASD themselves are at risk for atypical outcomes including behavioral challenges and therefore may be a useful population in which to investigate the structure of the DP in preschoolers., Methods: We sought to examine the factor structure and predictors of the DP in a sample enriched for a wide range of phenotypic variation-36-month-olds with and without family histories of ASD-and to determine whether children with genetic liability for ASD are at risk for a phenotype characterized by elevated dysregulation. Data were collected from 415 children with (n = 253) and without (n = 162) an older sibling with ASD, all without ASD themselves, at 18, 24, and 36 months of age., Results: Our findings replicate prior reports, conducted in predominantly clinically referred and older samples, supporting the superiority of a bifactor model of the DP in the preschool period compared to the second-order and one-factor models. Examiner ratings were longitudinally and concurrently associated with the DP at 36 months of age. Family history of ASD was associated with higher dysregulation in the Anxious/Depressed dimension., Conclusions: These findings support the relevance of examining the structure of psychopathology in preschoolers and suggest that examiner observations as early as 18 months of age, particularly of overactivity, may help identify risk for later DP-related concerns. Non-ASD preschoolers with family histories of ASD may be at risk for a phenotype characterized by elevated dysregulation particularly in the Anxious/Depressed dimension by age 3., (© 2018 Association for Child and Adolescent Mental Health.)

Several sponges from American Samoa, collected by the Coral Reef Research Foundation, Republic of Palau, were tentatively identified by one of us as Acanthotetilla cf seychellensis (Thomas 1973), due to the possession of relatively small acanthose oxeas, compared to those of other species of the genus Acanthotetilla Burton 1959. These sponges were later compared to Cinachyrella australiensis (Carter 1886), taking into account the lack of conspicuous spination on the acanthose oxeas and general features of spiculation and skeletal organisation. The specimens were later considered to represent a new species of the genus Cinachyrella Wilson 1925, after a careful comparison was made between the American Samoan specimens and C. australiensis which also contains small acanthose oxeas. Several recent molecular phylogenetic studies have confirmed the generic assignment of one of the American Samoan specimens as belonging to Cinachyrella. Cinachyrella anatriaenilla sp. nov., described herein, is the fifth of 40 Cinachyrella spp. that contain lightly spined microacanthoxeas.

Introduction: Accurate delivery of radiation while reducing dose to organs at risk is essential in prostate treatment. The Calypso motion management system detects and corrects both inter- and intra-fraction motion which offers potential benefits over standard alignment to fiducial markers. The aims of this study were to implement Calypso with Dynamic Edge™ gating and to assess both the motion seen, and interventions required., Methods: An implementation group was formed which assessed changes needed to standard workflows. Three patients had Calypso beacons inserted into their prostate. All patients were treated using volumetric modulated arc therapy to a dose of 80 Gy in 40 fractions. Standard inter-fraction motion correction using either kilovoltage (kV) orthogonal paired imaging or cone beam computed tomography (CBCT) image-guided radiotherapy techniques, were used along with the Calypso system to compare accuracy. A gating threshold of >0.5 cm was used during treatment. Workflow variations along with inter- and intra-fraction motion and interventions required were assessed., Results: A total of 116 fractions were treated using Calypso with Dynamic Edge™ gating. There was a strong concordance between aligning beacons using kV orthogonal imaging or CBCT and Calypso (mean variation ≤0.06 cm). The mean intra-fraction motion detected was ≤0.2 cm in all directions with the largest motion recorded being 2.2 cm in the left direction while the treatment beam was off. Prostate rotation was largest in the pitch direction and 28 fractions exceeded the 10° tolerance. A total of 78 couch shift corrections of ≥0.3 cm were required, usually following standard imaging, and before treatment starting. Three gating events due to intra-fraction motion occurred during treatment., Conclusions: Intra-fraction motion monitoring with Calypso was successfully implemented. Greatest movement was seen between time of standard imaging and treatment starting with more than half the treatments requiring a ≥0.3 cm adjustment. This would not have been detected without intra-fraction monitoring., (© 2017 The Authors. Journal of Medical Radiation Sciences published by Wiley Publishing Asia Pty Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.)

Antibacterial-guided fractionation of the Dictyoceratid sponges Lamellodysidea sp. and two samples of Dysidea granulosa yielded 14 polybrominated, diphenyl ethers including one new methoxy-containing compound (8). Their structures were elucidated by interpretation of spectroscopic data of the natural product and their methoxy derivatives. Most of the compounds showed strong antimicrobial activity with low- to sub-microgram mL(-1) minimum inhibitory concentrations against drug-susceptible and drug-resistant strains of Staphylococcus aureus and Enterococcus faecium, and two compounds inhibited Escherichia coli in a structure-dependent manner.

Context and Objective: Living kidney donation accounts for approximately half of all kidney transplantation in many countries and is central to health policy focused on increasing organ supply. However, little examination of the economic consequences of living kidney donation has been undertaken from the perspective of donors themselves. This article documents living kidney donors' views regarding recompense and payment for organ donation, based on their experience., Participants: Twenty-five living kidney donors from New Zealand participated in this study., Methods: This qualitative study, based on thematic analysis, uses semi-structured in-depth interviews to examine the experiences of living kidney donors. Themes were organized around altruism and the 'gift', perceptions of shared corporeality and identity, and donor support., Results: Most participants agreed the donation process was costly in terms of time and money. Many incurred personal costs, and some experienced financial hardship. All the participants viewed financial hardship as a barrier to organ donation and favoured recompense for direct and indirect costs. Most did not support payment for organs, and none supported commercialization., Discussion and Conclusions: The findings show that framing organ donation as a 'gift' can stymie discussion about reciprocity, remuneration and exchange, making talk about financial recompense difficult. Financial well-being, nonetheless, has implications for the ability to care for self and others post-operatively. We conclude that the economic consequences for living kidney donors in jurisdictions where recompense for direct and indirect costs is insufficient are unfair. Review of financial assistance for live organ donors is therefore recommended., (© 2014 John Wiley & Sons Ltd.)

Background: There is limited information available on the optimal Planning Target Volume (PTV) expansions and image guidance for post-prostatectomy intensity modulated radiotherapy (PP-IMRT). As the prostate bed does not move in a uniform manner, there is a rationale for anisotropic PTV margins with matching to soft tissue. The aim of this study is to find the combination of PTV expansion and image guidance policy for PP-IMRT that provides the best balance of target coverage whilst minimising dose to the organs at risk., Methods: The Cone Beam CT (CBCT) images (n = 377) of 40 patients who received PP-IMRT with daily online alignment to bony anatomy (BA) were reviewed. Six different PTV expansions were assessed: 3 published PTV expansions (0.5 cm uniform, 1 cm uniform, and 1 + 0.5 cm posterior) and 3 further anisotropic PTV expansions (Northern Sydney Cancer Centre (NSCC), van Herk, and smaller anisotropic). Each was assessed for size, bladder and rectum coverage and geographic miss. Each CBCT was rematched using a superior soft tissue (SST) and averaged soft tissue (AST) match. Potential geographic miss was assessed using all PTV expansions except the van Herk margin., Results: The 0.5 cm uniform expansion yielded the smallest PTV (median volume = 222.3 cc) and the 1 cm uniform expansion yielded the largest (361.7 cc). The Van Herk expansion includes the largest amount of bladder (28.0 %) and rectum (36.0 %) and the 0.5 cm uniform expansion the smallest (17.1 % bladder; 10.2 % rectum). The van Herk PTV expansion had the least geographic miss with BA matching (4.2 %) and the 0.5 cm uniform margin (28.4 %) the greatest. BA matching resulted in the highest geographic miss rate for all PTVs, followed by SST matching and AST matching. Changing from BA to an AST match decreases potential geographic miss by half to two thirds, depending on the PTV expansion, to <10 % for all PTV expansions. When using the smaller anisotropic PTV expansion, AST matching would reduce the geographic miss rate from 21.0 % with BA matching down to 5.6 %., Conclusions: Our results suggest the optimal PTV expansion and image guidance policy for PP-IMRT is daily average soft tissue matching using CBCT scans with a small anisotropic PTV expansion of 0.5 cm in all directions apart from a 1 cm expansion in the anterior-posterior direction in the upper prostate bed. Care must be taken to ensure adequate training of Radiation Therapists to perform soft tissue matching with CBCT scans.

Objectives: Yersiniosis, a foodborne infection of zoonotic origin caused by the bacteria Yersinia enterocolitica and Yersinia pseudotuberculosis, is a reportable disease in 38 states. Both sporadic and foodborne outbreaks of yersiniosis have been reported in the U.S., with annual occurrence of an estimated 98,000 episodes of illness, 533 hospitalizations, and 29 deaths. We analyzed surveillance data from nine non-FoodNet-participating U.S. states during the period 2005-2011 to describe the epidemiology of this disease., Methods: As part of a passive surveillance system, laboratory-confirmed cases of yersiniosis were reported to state health departments in Arizona, Illinois, Michigan, Missouri, Nebraska, North Carolina, South Carolina, Washington, and Wisconsin. We calculated overall, age-, and race-specific annual incidence rates per 100,000 population using 2010 Census data as the denominator. We used Poisson regression to examine seasonal variation and annual incidence trends by race, age group, and overall., Results: The average annual incidence of yersiniosis was 0.16 cases per 100,000 population during 2005-2011. We observed a statistically significant decreasing annual trend of yersiniosis incidence among African Americans <5 years of age (p<0.01), whereas white people aged 19-64 years (p=0.08) and Hispanic people (p=0.05) had an overall increasing annual incidence of yersiniosis. We observed higher incidence during October-December (p<0.01) and January-March (p=0.03) quarters among African Americans, whereas white people had a higher incidence during April-June (p=0.05)., Conclusion: This multistate analysis revealed differences in the epidemiology of yersiniosis by race/ethnicity that may be useful for future research and prevention efforts. While this study was consistent with the FoodNet report in recognizing the high and declining incidence among African American children and winter seasonality among African Americans, our study also identified April-June seasonality among the white population.

Background: An operating room (OR) environment is challenging and complicated. At any given time, several vital tasks are being performed by skilled individuals, including physicians, nurses, and ancillary staff. There is a potential for multifactorial mistakes; many arise because of communication issues., Methods: To evaluate the current state of perceptions of interdisciplinary communication in an OR setting, a survey was developed and administered to four academic residency training departments of anesthesiology in a single U.S. state., Results: The results of this survey show that perceived poor communication within the OR leads to a lack of emphasis on a multidisciplinary approach to patient care in the OR., Conclusions: Survey data can be used internally to identify shortcomings in communication at a facility, to stress the importance of communication, and to serve as a powerful education tool to potentially improve patient care. Through this type of survey, which emphasizes communication in the OR, stakeholders can work more effectively to improve patient care and decrease adverse outcomes in the hospital environment.

Variations in rectal and bladder filling can create a tilt of the prostate bed, which generates the potential for a geographic miss during postprostatectomy radiotherapy. The aim of this study is to assess the effect that bladder and rectum filling has on planning target volume angle, to determine a method to assess prostate bed tilt leading to potential geographic miss, and to discuss possible implementation issues. The cone-beam computed tomography images (n = 377) of 40 patients who received postprostatectomy radiotherapy with intensity-modulated radiotherapy were reviewed. The amount of tilt in the prostate bed was defined as the angle change between 2 surgical clips, one in the upper prostate bed and another in the lower. A potential geographic miss was defined as movement of any clip of more than 1cm in any direction or 0.5 cm posteriorly when aligned to bone anatomy. Variations in bladder and rectum size were correlated with the degree of prostate bed tilt, and the rate of potential geographic miss was determined. A possible clinical use of prostate bed tilt was then assessed for different imaging techniques. A tilt of more than 10° was seen in 20.2% of images, which resulted in a 57.9% geographic miss rate of the superior clip. When tilt remained within 10°, there was only a 9% rate of geographic miss. Potential geographic miss of the inferior surgical clip was rare, occurring in only 1.9% of all images reviewed. The most common occurrence when the prostate bed tilt increased by more than 10° was a smaller bladder and larger rectum (6.4% of all images). The most common occurrence when the prostate bed tilt decreased by more than 10° was a larger bladder and smaller rectum (1.3% of all images). Significant prostate bed tilt (>± 10°) occurred in more than 20% of images, creating a 58% rate of geographic miss. Greatest prostate bed tilt occurred when the bladder size increased or reduced by more than 2 cm or the superior rectum size increased by more than 1.5 cm or reduced by more than 1cm from the planned size. Using prostate bed tilt could be an effective measurement for assessing potential geographic miss on orthogonal images if volumetric imaging is unavailable., (Copyright © 2014 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Introduction: Standard post-prostatectomy radiotherapy (PPRT) image verification uses bony anatomy alignment. However, the prostate bed (PB) moves independently of bony anatomy. Cone beam computed tomography (CBCT) can be used to soft tissue match, so radiation therapists (RTs) must understand pelvic anatomy and PPRT clinical target volumes (CTV). The aims of this study are to define regions of interest (ROI) to be used in soft tissue matching image guidance and determine their visibility on planning CT (PCT) and CBCT., Methods: Published CTV guidelines were used to select ROIs. The PCT scans (n = 23) and CBCT scans (n = 105) of 23 post-prostatectomy patients were reviewed. Details on ROI identification were recorded., Results: Eighteen patients had surgical clips. All ROIs were identified on PCTs at least 90% of the time apart from mesorectal fascia (MF) (87%) due to superior image quality. When surgical clips are present, the seminal vesicle bed (SVB) was only seen in 2.3% of CBCTs and MF was unidentifiable. Most other structures were well identified on CBCT. The anterior rectal wall (ARW) was identified in 81.4% of images and penile bulb (PB) in 68.6%. In the absence of surgical clips, the MF and SVB were always identified; the ARW was identified in 89.5% of CBCTs and PB in 73.7%., Conclusions: Surgical clips should be used as ROIs when present to define SVB and MF. In the absence of clips, SVB, MF and ARW can be used. RTs must have a strong knowledge of soft tissue anatomy and PPRT CTV to ensure coverage and enable soft tissue matching.

Background and Purpose: Accuracy when delivering post-prostatectomy intensity modulated radiotherapy (IMRT) is crucial. The aims of this study were to quantify prostate bed movement and determine what amount of bladder or rectum size variation creates the potential for geographic miss., Methods and Materials: The Cone Beam CT (CBCT) images (n=377) of forty patients who received post-prostatectomy IMRT with daily on-line alignment to bony anatomy were reviewed. Prostate bed movement was estimated using the location of surgical clips in the upper and lower sections of the PTV and correlated with rectal and bladder filling (defined as changes in the cross sectional diameter at defined levels). The number of potential geographic misses caused by bladder and rectum variation was calculated assuming a uniform CTV to PTV expansion of 1cm except 0.5 cm posteriorly., Results: Variations in bladder filling of >2 cm larger, ±1 cm, or >2 cm smaller occurred in 3.4%, 56.2%, and 15.1% of images respectively with potential geographic misses in the upper prostate bed of 61.5%, 9.9% and 26.3% respectively. Variations in rectal filling in the upper prostate bed of >1.5 cm larger, 1.5 cm larger to 1cm smaller, and >1cm smaller occurred in 17.2%, 75.6%, and 7.2% of images respectively. These variations resulted in geographic misses in the upper prostate bed in 29.2%, 12.3%, and 63.0% of images respectively. Variations in bladder and rectal filling in the lower prostate bed region had minimal impact on geographic misses., Conclusions: Bladder and rectal size changes at treatment affect prostate bed coverage, especially in the upper aspect of the prostate bed. The greatest potential for geographic miss occurred when either the bladder increased in size or when the rectum became smaller. Ensuring a full bladder and empty rectum at simulation will minimise this risk. Our data also support anisotropic PTV margins with larger margins superiorly than inferiorly., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Introduction: There is little data to guide radiation oncologists on appropriate margin selection in the post-prostatectomy setting. The aim of this study was to quantify interfraction variation in motion of the prostate bed to determine these margins., Methods: The superior and inferior surgical clips in the prostate bed were tracked on pretreatment cone beam CT images (n = 377) for 40 patients who had received post-prostatectomy radiotherapy. Prostate bed motion was calculated for the upper and lower segments by measuring the position of surgical clips located close to midline relative to bony anatomy in the axial (translational) and sagittal (tilt) planes. The frequency of potential geographic misses was calculated for either 1 cm or 0.5 cm posterior planning target volume margins., Results: The mean magnitude of movement of the prostate bed in the anterior-posterior, superior-inferior and left-right planes, respectively, were as follows: upper portion, 0.50 cm, 0.28 cm, 0.10 cm; lower portion, 0.18 cm, 0.18 cm, 0.08 cm. The random and systematic errors, respectively, of the prostate bed motion in the anterior-posterior, superior-inferior and left-right planes, respectively, were as follows: upper portion, 0.47 cm and 0.50 cm, 0.28 cm and 0.27 cm, 0.11 cm and 0.11 cm; lower portion, 0.17 cm and 0.18 cm, 0.17 cm and 0.19 cm, 0.08 cm and 0.10 cm. Most geographic misses occurred in the upper prostate bed in the anterior-posterior plane. The median prostate bed tilt was 1.8° (range -23.4° to 42.3°)., Conclusions: Variability was seen in all planes for the movement of both surgical clips. The greatest movement occurred in the anterior-posterior plane in the upper prostate bed, which could cause geographic miss of treatment delivery. The variability in the movement of the superior and inferior clips indicates a prostate bed tilt that would be difficult to correct with standard online matching techniques. This creates a strong argument for using anisotropic planning target volume margins in post-prostatectomy radiotherapy., (© 2013 The Royal Australian and New Zealand College of Radiologists.)

Circadian clocks are 24-h timekeeping mechanisms, which have evolved in plants, animals, fungi and bacteria to anticipate changes in light and temperature associated with the rotation of the Earth. The current paradigm to explain how biological clocks provide timing information is based on multiple interlocking transcription-translation negative feedback loops (TTFL), which drive rhythmic gene expression and circadian behaviour of growth and physiology. Metabolism is an important circadian output, which in plants includes photosynthesis, starch metabolism, nutrient assimilation and redox homeostasis. There is increasing evidence in a range of organisms that these metabolic outputs can also contribute to circadian timing and might also comprise independent circadian oscillators. In this review, we summarise the mechanisms of circadian regulation of metabolism by TTFL and consider increasing evidence that rhythmic metabolism contributes to the circadian network. We highlight how this might be relevant to plant circadian clock function., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Aim: To compare online position verification strategies with offline correction protocols for patients undergoing definitive prostate radiotherapy., Materials and Methods: We analysed 50 patients with implanted fiducial markers undergoing curative prostate radiation treatment, all of whom underwent daily kilovoltage imaging using an on-board imager. For each treatment, patients were set-up initially with skin tattoos and in-room lasers. Orthogonal on-board imager images were acquired and the couch shift to match both bony anatomy and the fiducial markers recorded. The set-up error using skin tattoos and offline bone correction was compared with online bone correction. The fiducial markers were used as the reference., Results: Data from 1923 fractions were analysed. The systematic error was ≤1 mm for all protocols. The average random error was 2-3mm for online bony correction and 3-5mm for skin tattoos or offline-bone. Online-bone showed a significant improvement compared with offline-bone in the number of patients with >5mm set-up errors for >10% (P<0.001) and >20% (P<0.003) of their fractions., Conclusions: Online correction to bony anatomy reduces both systematic and random set-up error in patients undergoing prostate radiotherapy, and is superior to offline correction methods for those patients not suitable for fiducial markers or daily soft-tissue imaging., (Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

The Earth's rotation and its orbit around the Sun leads to continual changes in the environment. Many organisms, including plants and animals, have evolved circadian clocks that anticipate these changes in light, temperature, and seasons in order to optimize growth and physiology. Circadian timing is thought to derive from a molecular oscillator that is present in every plant cell. A central aspect of the circadian oscillator is the presence of transcription translation loops (TTLs) that provide negative feedback to generate circadian rhythms. This review examines the evidence that the 24 h circadian clocks of plants regulate the fluxes of solutes and how changes in solute concentrations can also provide feedback to modulate the behaviour of the molecular oscillator. It highlights recent advances that demonstrate interactions between components of TTLs and regulation of solute concentration and transport. How rhythmic control of water fluxes, ions such as K(+), metabolic solutes such as sucrose, micronutrients, and signalling molecules, including Ca(2+), might contribute to optimizing the physiology of the plant is discussed.

A new sulfated cyclic depsipeptide, termed mutremdamide A, and six new highly N-methylated peptides, termed koshikamides C-H, were isolated from different deep-water specimens of Theonella swinhoei and Theonella cupola. Their structures were determined using extensive 2D NMR, ESI, or CDESI and QTOF-MS/MS experiments and absolute configurations established by quantum mechanical calculations, advanced Marfey's method, and chiral HPLC. Mutremdamide A displays a rare 2-amino-3-(2-hydroxyphenyl)propanoic acid and a new N(delta)-carbamoyl-beta-sulfated asparagine. Koshikamides C-E are linear undecapeptides, and koshikamides F-H are 17-residue depsipeptides containing a 10-residue macrolactone. Koshikamides F and G differ from B and H in part by the presence of the conjugated unit 2-(3-amino-5-oxopyrrolidin-2-ylidene)propanoic acid. Cyclic koshikamides F and H inhibited HIV-1 entry at low micromolar concentrations while their linear counterparts were inactive. The Theonella collections studied here are distinguished by co-occurrence of mutremdamide A, koshikamides, and theonellamides, the combination of which appears to define a new Theonella chemotype that can be found in deeper waters.

Background: The deprivation gap for breast cancer survival remains unexplained by stage at presentation, treatment, or co-morbidities. We hypothesised that p53 mutation might contribute to the impaired outcome observed in patients from deprived communities., Methods: p53 mutation status was determined using the Roche Amplichip research test in 246 women with primary breast cancer attending a single cancer centre and related to deprivation, pathology, overall, and disease-free survival., Results: p53 mutation, identified in 64/246 (26%) of cancers, was most common in 10 out of 17 (58.8%) of the lowest (10th) deprivation decile. Those patients with p53 mutation in the 10th decile had a significantly worse disease-free survival of only 20% at 5 years (Kaplan-Meier logrank chi(2)=6.050, P=0.014) and worse overall survival of 24% at 5 years (Kaplan-Meier logrank chi(2)=6.791, P=0.009) than women of deciles 1-9 with p53 mutation (c.f. 56% and 72%, respectively) or patients in the 10th decile with wild-type p53 (no disease relapse or deaths)., Conclusion: p53 mutation in breast cancer is associated with socio-economic deprivation and may provide a molecular basis, with therapeutic implications, for the poorer outcome in women from deprived communities.

Understanding El Niño/Southern Oscillation (ENSO) and its biological consequences is hindered by a lack of high-resolution, long-term data from the tropical western Pacific. We describe a preliminary, 6 year dataset that shows tightly coupled ENSO-related bio-physical dynamics in a seawater lake in Palau, Micronesia. The lake is more strongly stratified during La Niña than El Niño conditions, temperature anomalies in the lake co-vary strongly with the Niño 3.4 climate index, and the abundance of the dominant member of the pelagic community, an endemic subspecies of zooxanthellate jellyfish, is temperature associated. These results have broad relevance because the lake: (i) illustrates an ENSO signal that is partly obscured in surrounding semi-enclosed lagoon waters and, therefore, (ii) may provide a model system for studying the effects of climate change on community evolution and cnidarian-zooxanthellae symbioses, which (iii) should be traceable throughout the Holocene because the lake harbours a high quality sediment record; the sediment record should (iv) provide a sensitive and regionally unique record of Holocene climate relevant to predicting ENSO responses to future global climate change and, finally, (v) seawater lake ecosystems elsewhere in the Pacific may hold similar potential for past, present, and predictive measurements of climate variation and ecosystem response.

Objectives: South Carolina mandates reporting of animal bites and manages distribution of biologics for rabies postexposure prophylaxis (PEP). Incidence and epidemiologic characteristics of potential human rabies exposures and preventive treatment in South Carolina from 1993 through 2002 were examined to help assess the burden of PEP in the state and determine if the incidence of rabies exposures has changed over time., Methods: Data on animal exposure investigations and PEP administration at the state and county level were examined, and the annual incidences of potential rabies exposures and human PEP courses were calculated., Results: The incidence of animal exposures for which investigations were initiated was 297.9 per 100,000 population per year, and the incidence of PEP was 10.6 per 100,000 population per year. At the county level, the incidence of PEP appeared inversely correlated with the population density. Most courses of PEP were administered following exposures to domestic species, although these animals accounted for only a small proportion of rabid animals in the state. The annual PEP incidence was similar throughout the study period, but it was markedly higher than estimates from 1981 (< 5/100,000 population per year)., Conclusions: The incidence of PEP in South Carolina is higher than previously thought, and these findings suggest that incidence extrapolations for other states and at the national level may be underestimated. An accurate estimation of the incidence of PEP and an understanding of rabies epidemiology is important at the state level to allow for better public health planning.

To provide a potentially therapeutic intervention and to collect clinical and laboratory data during an outbreak of hantavirus pulmonary syndrome (HPS), 140 patients from the United States with suspected HPS were enrolled for investigational intravenous ribavirin treatment. HPS was subsequently laboratory confirmed in 30 persons and not confirmed in 105 persons with adequate specimens. Patients with HPS were significantly more likely than were hantavirus-negative patients to report myalgias from onset of symptoms through hospitalization, nausea at outpatient presentation, and diarrhea and nausea at the time of hospitalization; they were significantly less likely to report respiratory symptoms early in the illness. The groups did not differ with regard to time from the onset of illness to the point at which they sought care; time from onset, hospitalization, or enrollment to death was significantly shorter for patients with HPS. At the time of hospitalization, patients with HPS more commonly had myelocytes, metamyelocytes, or promyelocytes on a peripheral blood smear, and significantly more of them had thrombocytopenia, hemoconcentration, and hypocapnia. Patterns of clinical symptoms, the pace of clinical evolution, and specific clinical laboratory parameters discriminated between these 2 groups.

Intravenous ribavirin was provided non-selectively for investigational open-label use among persons with suspected hantavirus pulmonary syndrome (HPS) in the United States between 4 June 1993 and 1 September 1994. Therapy was initiated prior to laboratory confirmation of hantavirus infection because most deaths from HPS occur within 48 h of hospitalization. Thirty patients with confirmed HPS, 105 patients without HPS and 5 patients without adequate diagnostic testing for HPS were enrolled. This observational study arguably provides the most complete information available on ribavirin-associated adverse effects. Although ribavirin was generally well tolerated, 71% of recipients became anaemic and 19% underwent transfusion. An apparent excess of hyperamylasaemia/pancreatitis was either therapy-associated or due to enrollment bias. The 30 enrolled HPS patients had a case-fatality rate of 47% (14/30). It is not possible to assess efficacy with this study design. However, comparison of survival curves for the 30 enrolled HPS patients and 34 patients who developed HPS during the same time period but were not enrolled did not suggest an appreciable drug effect. A randomized, placebo-controlled trial that enrolls patients during the prodrome phase would be necessary to assess the efficacy and further define the safety of intravenous ribavirin for HPS.

Bond strengths between disinfected putty impressions and subsequent wash applications were determined in specimens made to simulate clinically an interrupted two-step impression technique. The effect of a disinfectant on the bond strength between a disinfected wash impression and a subsequent wash application was also evaluated to simulate perfecting a disinfected final impression clinically. Vinyl polysiloxane (putty or wash) and polyether (wash only) impression materials were placed in perforated metal cylinders, allowed to set, and dipped in an iodine or glutaraldehyde disinfectant. Wash material was then applied to the disinfected material by use of another metal cylinder and allowed to set before the specimen was tested in tensile mode. Significant decreases in bond strengths were found in both clinical simulations but were limited to specific impression material and disinfectant combinations.

Inorganic mercury causes systemic autoimmunity and/or immune-complex deposits in strains of mice carrying certain H-2 haplotypes, for example H-2s and H-2d. This study aimed at describing the genetic mechanisms regulating these reactions. Inbred SJL, C57BL/6J (B6), C57BL/10J (B10), and DBA mice, F1(SJL x DBA), F1(SJL x B6), and F2(SJL x B6) hybrids, and mice derived from a backcross of SJL or B6 mice to F1(SJL x B6) hybrids were given subcutaneous injections of either 1.6 mg HgCl2/kg body wt or 0.1 ml NaCl every third day for 6 weeks. SJL mice developed a high titer of serum antinucleolar antibodies (ANoA) of the IgG class targeting the nucleolar protein fibrillarin and a significantly increased titer of IgG and C3 colocalized as granular deposits in the renal mesangium and vessel walls. The B6 and DBA strains lacked ANoA and showed no increase in titers of immune deposits. Nine percent of mercury-treated F1(SJL x DBA) hybrids developed IgG-ANoA which were of a low titer, and only occasional hybrids showed an increased titer of granular mesangial IgG deposits. Mercury treatment induced ANoA of low titer in 41% of F1(SJL x B6) hybrids, and 24% had increased granular mesangial immune deposits. Four of 61 mercury-treated BC-[SJL x F1(SJL x B6)] mice showed ANoA which were of a high titer and targeted the nucleolar protein fibrillarin. ANoA were not found in 55 mercury-treated F2(SJL x B6) hybrids or in 56 mercury-treated mice derived from a backcross of B6 mice to F1(SJL x B6) hybrids. Increased mesangial immune deposits were regularly accompanied by vessel wall deposits in F1- and F2(SJL x B6) hybrids, but only 53% of BC(SJL x F1[SJL x B6]) mice with increased mesangial deposits had vessel wall deposits. Vessel wall immune deposits were only present in mice with increased mesangial deposits. A majority of mice which developed significantly increased titers of mesangial IC deposits showed no ANoA. In conclusion, the susceptibility in SJL mice to develop ANoA during mercury treatment, which has been shown to reside in the H-2A locus, was codominantly inherited in a cross with mice carrying the H-2b and H2d haplotypes. Non-H-2 genes dampened ANoA expression to a degree which varied between the strains. Since renal vessel and mesangial IC deposits developed in backcross mice lacking serum ANoA, these deposits must contain IC not related to fibrillarin-antifibrillarin.(ABSTRACT TRUNCATED AT 400 WORDS)

Inbred, congenic, and intra-H-2-recombinant mouse strains were given subcutaneous injections of either 1.6 mg HgCl2/kg body wt or 0.1 ml NaCl thrice weekly for 5-6 weeks. Mercury-treated mice from strains carrying the H-2s haplotype developed antinucleolar antibodies (ANoA), which targeted the 34-kDa nucleolar protein fibrillarin, and in some instances also nucleolar proteins of 60-70 and 10-15 kDa, the latter corresponding to histones. Strains with H-2b and H-2d haplotypes were resistant to induction of ANoA. The susceptibility to development of AnoA/antifibrillarin antibodies (AFA) was mapped to the H-2A-region using intra-H-2-recombinant strains. We were not able to confirm earlier reports that expression of H-2E genes dampens the development of ANoA. Mercury treatment caused a substantial increase in the titer of antichromatin (ACA) and/or antihistone (AHA) antibodies in a fraction of SJL/J, A.SW, A.TH, B10.S, and B10.HTT mice (H-2s), and in A/J (H-2k) mice, whereas mice from the C57BL/6J and C57BL/10J (H-2b), and the DBA and BALB/c (H-2d) strains were low or nonresponders. The development of AHA and ACA could not be linked to the H-2 complex. A significant, substantial increase of granular mesangial and systemic vessel wall IgG deposits occurred in mice with serum ANoA/AFA. However, the B10.S(9R) and B10.HTT strains, which express the H-2E genes, developed only an intermediately increased titer of mesangial IgG deposits. Systemic vessel wall IgG deposits occurred in only 60-80% of the B10.S(9R) mice and in none of the B10.HTT mice. This contrasted with the high titer of mesangial IgG deposits and uniform development of systemic vessel wall IgG deposits observed in B10.S mice not expressing H-2E. Mice with mesangial IgG deposits showed a mild glomerulonephritis. There was no systemic vasculitis. The susceptibility to development of ANoA, AHA, ACA, and systemic, granular IgG deposits in the B10.S strain was influenced by the sex, since males showed less uniform development of these immunopathologic features than females.

A technique is described for the organ culture of Rhipicephalus appendiculatus ticks. Whole, unfed adult ticks with the dorsal integument removed, known as backless tick explants, were cultured in enriched Leibovitz' L-15 medium in which they remained active for at least 32 days at 28 degrees C and 9 days at 36 degrees C. Development of Theileria parva, as demonstrated by methyl green-pyronin staining, occurred in the salivary glands of infected backless tick explants held for 8 days at 28 degrees C or 3 days at 36 degrees C. Maturation in vitro of T. parva in backless tick explants was compared with that in cultured excised salivary glands. After 3-7 days at 36 degrees C glands from backless tick explants and excised salivary glands showed similar numbers of infected acini per infected tick. However, after 12 days at 28 degrees C backless tick explants showed 20-30 times as many infected acini per infected tick as excised salivary glands, in two experiments. No assessment was made of degree of parasite maturity or infectivity. It was concluded that both organ culture techniques supported development in vitro of the salivary gland stages of T. parva, but the backless tick explant technique was simpler and gave generally better results than culture of excised salivary glands.

Methods for infecting Rhipicephalus appendiculatus ticks with Theileria parva by injection and by artificial feeding were confirmed and compared. The injection method proved simpler and at best as effective and suggested improvements are described.

Procedures are described for the colonization of Hyalomma anatolicum anatolicum ticks using gerbils, rabbits and cattle as hosts. On rabbits H. a. anatolicum undergoes a two-host cycle but methods are described for obtaining either unfed or engorged nymphs. Data are given on the life cycle timings and the numbers and timings of tick feeding regimes. The infection of H. a. anatolicum with two strains of Theileria annulata is described and methods given for monitoring the development and survival of T. annulata in H. a. anatolicum. Data are presented indicating the optimum maintenance conditions for T. annulata in H. a. anatolicum. Piroplasm parasitaemias in cattle greater than 2% gave high infection rates in adult ticks if engorged nymphs were moulted at 28 degrees C for 28 days. The Theileria will survive for ten months in such adults stored at 12 degrees C after moult, and when fed the ticks will produce maximum numbers of sporozoites on the third day of feeding, whatever their age. The moult of engorged nymphs is retarded at 18 degrees C but the Theileria in such ticks will develop normally when the ticks are moulted at 28 degrees C after four months storage at 18 degrees C.

A simplified method for methyl green pyronin staining is described for Theileria parva and T. annulata in whole salivary glands of Rhipicephalus appendiculatus and Hyalomma anatolicum subspecies respectively. The stain gives results comparable with Feulgen staining and can be used after the ticks have been in cold storage for 3 days. There is considerable variability in the rate and intensity of infection of these ticks with theilerial parasites and it is concluded that the method permits large samples (60 ticks per person per day) to be examined to overcome this variability when assessing infection quantitatively.

Serum prolactin levels were significantly lower in mice exposed to alcohol for 28 days than they were in controls, and the latency period for adenocarcinoma development was significantly shorter in the alcohol-exposed animals.

The joint administration of 2 ppm of arsenic as arsenite and of 2 ppm of selenium as selenite in the drinking water of inbred female C3H/St mice increases the incidence of spontaneous mammary adenocarcinoma significantly over the simultaneous controls and animals receiving 2 ppm As as arsenite or 2 ppm Se as selenite alone, indicating that arsenic abolishes the anticarcinogenic effect of selenium. Arsenite caused a significant increase of the tumor growth rates and raised the incidence of multiple tumors. The tumor growth rates in the As-Se group were also increased, but the incidence of multiple tumors was lower than in the 2 ppm As group.

The development at 28 degrees C of Theileria annulata (Hissar) in the salivary glands of its tick vector, Hyalomma anatolicum anatolicum, was studied using Giemsa-stained smears, methyl green-pyronin-stained preparations of whole glands, and electron microscopy. Nymphs which had engorged on T. annulata-infected calves showed kinetes in the haemolymph from Day 7 to Day 14 post engorgement, when all ticks had completed moult. Intracellular sporonts were observed within salivary gland acini from Day 7 onwards and these developed by rapid nuclear division and cytoplasmic proliferation to form primary sporoblasts. Further development was stimulated by feeding on a rabbit or by incubation at 36 degrees C. The primary sporoblasts appeared to become organized into membrane-bound subunits. Within 48 hours of attachment to the host, or 72 hours of 36 degrees C incubation, these units dissociated to form secondary sporoblasts. The final phase of development resulted in the progressive formation of discrete, uninuclear sporozoites within these secondary sporoblasts. No morphological differences were observed in parasite maturation between the fed and incubated groups although development was retarded by at least 24 hours in the latter. In the incubated group there was also a marked decrease in the degree of synchrony of development which resulted in fewer sporozoites being present at any one time.

1. Of 50 lateral condylar settings made, 10 were not accepted by the Whip-Mix articulator. 2. An improved method of obtaining lateral interocclusal records was described. 3. The Whip-Mix articulator is considered useful in diagnosis and treatment in prosthodontic procedures if one is aware of its limitations.

1. The effects of intraventricular injection of 6-hydroxydopamine (6-OHDA) on tyrosine hydroxylase activity, uptake of (3)H-noradrenaline and endogenous catecholamine concentration in rat hypothalamus and striatum were investigated at various times after the injection of 6-OHDA.2. In the hypothalamus after the injection of 250 mug of 6-OHDA there was a rapid decrease in tyrosine hydroxylase activity, (3)H-noradrenaline uptake and noradrenaline content, which was essentially complete within 2 hours.3. In the striatum after this dose of 6-OHDA there was a much slower reduction in tyrosine hydroxylase activity and (3)H-noradrenaline uptake during the first 48 h after drug injection. For the first 24 h the dopamine concentration in this brain area was increased significantly above control values, but had fallen below control values by 48 hours.4. After the injection of a smaller dose of 6-OHDA (25 mug) the only detectable change in the striatum was a rapid increase in the dopamine concentration. In the hypothalamus this dose induced a rapid depletion of noradrenaline, not accompanied initially by any significant reduction in tyrosine hydroxylase activity.5. These results are consistent with the hypothesis that 6-OHDA causes a rapid degeneration of catecholamine-containing nerve terminals in the central nervous system (CNS). These degenerative changes, indicated by the loss of tyrosine hydroxylase and noradrenaline uptake sites, did not appear to be preceded by an initial displacement of endogenous catecholamines by 6-OHDA, except possibly at early times after the administration of small doses of the drug.