The use of a mini-ridge filter with cyclotron-based pencil beam scanning proton therapy.

BACKGROUND: Pencil beam scanning (PBS) proton therapy allows for far superior dose conformality compared with passive scattering techniques. However, one drawback of PBS is that the beam delivery time can be long, particularly when treating superficial disease. Minimizing beam delivery time is important for patient comfort and precision of treatment delivery. Mini-ridge filters (MRF) have been shown to reduce beam delivery time for synchrotron-based PBS. Given that cyclotron systems are widely used in proton therapy it is necessary to investigate the potential clinical benefit of mini-ridge filters in such systems. PURPOSE: To demonstrate the clinical benefit of using a MRF to reduce beam delivery time for patients with large target volumes and superficial disease in cyclotron-based PBS proton therapy. METHODS: A MRF beam model was generated by simulating the effect of a MRF on our clinical beam data assuming a fixed snout position relative to the isocenter. The beam model was validated with a series of measurements. The model was used to optimize treatment plans in a water phantom and on six patient DICOM datasets to further study the effect of the MRF and for comparison with physician-approved clinical treatment plans. Beam delivery time was measured for six plans with and without the MRF to demonstrate the reduction achievable. Plans with and without MRF were reviewed to confirm clinical acceptability by a radiation oncologist. Patient-specific QA measurements were carried out with a two-dimensional ionization chamber array detector for one representative patient's plan optimized with the MRF beam model. RESULTS: Results show good agreement between the simulated beam model and measurements with mean and maximum deviations of 0.06 mm (0.45%) and 0.61 mm (4.9%). The increase in Bragg peak width (FWHM) ranged from 2.7 mm at 226 MeV to 6.1 mm at 70 MeV. The mean and maximum reduction in beam delivery time observed per field was 29.1 s (32.2%) and 79.7 s (55.3%). CONCLUSION: MRFs can be used to reduce treatment time in cyclotron-based PBS proton therapy without sacrificing plan quality. This is particularly beneficial for patients with large targets and superficial disease such as in breast cancer where treatment times are generally long, as well as patients treated with deep inspiration breath hold (DIBH).

Words of agency: Executed and observed vocal actions induce a temporal binding effect.

Humans generally experience a sense of agency over the outcomes produced by their motor actions. This has been well established in the case of manual actions that directly affect the physical environment. Vocalizations are also actions, but they typically have only indirect effects on the environment. In the present research, we explore whether the outcomes produced by vocalizations also elicit a sense of agency. In three experiments, using an interval reproduction task, we find that performing a vocal action that produced an auditory outcome caused participants to underestimate the amount of elapsed time between actions and outcomes (i.e., temporal binding), an implicit index of the sense of agency (Experiment 1). We also show that observing others produce vocal actions elicits temporal binding, but only when the observer has direct visual access to the vocal action being executed (Experiments 2 and 3). Taken together, our findings suggest that direct observation of an action is necessary to experience a temporal binding effect for actions performed by others, and that audio-visuomotor information may play a role in the generation of temporal compression experienced over observed actions (PsycInfo Database Record (c) 2021 APA, all rights reserved).

From Gaze Perception to Social Cognition: The Shared-Attention System.

When two people look at the same object in the environment and are aware of each other's attentional state, they find themselves in a shared-attention episode. This can occur through intentional or incidental signaling and, in either case, causes an exchange of information between the two parties about the environment and each other's mental states. In this article, we give an overview of what is known about the building blocks of shared attention (gaze perception and joint attention) and focus on bringing to bear new findings on the initiation of shared attention that complement knowledge about gaze following and incorporate new insights from research into the sense of agency. We also present a neurocognitive model, incorporating first-, second-, and third-order social cognitive processes (the shared-attention system, or SAS), building on previous models and approaches. The SAS model aims to encompass perceptual, cognitive, and affective processes that contribute to and follow on from the establishment of shared attention. These processes include fundamental components of social cognition such as reward, affective evaluation, agency, empathy, and theory of mind.

The N170 event-related potential differentiates congruent and incongruent gaze responses in gaze leading.

To facilitate social interactions, humans need to process the responses that other people make to their actions, including eye movements that could establish joint attention. Here, we investigated the neurophysiological correlates of the processing of observed gaze responses following the participants' own eye movement. These observed gaze responses could either establish, or fail to establish, joint attention. We implemented a gaze leading paradigm in which participants made a saccade from an on-screen face to an object, followed by the on-screen face either making a congruent or incongruent gaze shift. An N170 event-related potential was elicited by the peripherally located gaze shift stimulus. Critically, the N170 was greater for joint attention than non-joint gaze both when task-irrelevant (Experiment 1) and task-relevant (Experiment 2). These data suggest for the first time that the neurocognitive system responsible for structural encoding of face stimuli is affected by the establishment of participant-initiated joint attention.

"Improving Access to Early Childhood Developmental Surveillance for Children from Culturally and Linguistically Diverse (CALD) Background".

INTRODUCTION: Developmental vulnerabilities in pre-school aged children from culturally and linguistically diverse (CALD) backgrounds with low English proficiency are less likely to be identified through universal developmental surveillance. Barriers include low parental health literacy and low rates of attendance to mainstream child and family health services. Late detection of developmental vulnerabilities can have lifelong impacts on life trajectory. METHOD: Integrated outreach early childhood developmental surveillance was trialled in South East Sydney by local health services with non-government organisations (NGO) delivering early childhood education and support. NGO staff were trained in Parents Evaluation of Developmental Status (PEDS), a validated developmental screening tool to explore parental/carer and provider concerns [1]. Families with children identified with developmental concerns by NGO staff were referred to co-located or visiting Child and Family Health Nurses (CFHN), community child health, speech pathology or developmental services for developmental screening, assessment and/or care planning. RESULTS: Integrated health and NGO services improved access to developmental surveillance for CALD families in a non-threatening environment enabled by co-locating CFHN, or through visits by paediatric medical/speech pathology staff to participating playgroups. CONCLUSIONS AND DISCUSSION: Integration supported vulnerable families from CALD backgrounds to access developmental surveillance through child and family health services but required flexibility and adjustments by all involved.

Eyes that bind us: Gaze leading induces an implicit sense of agency.

Humans feel a sense of agency over the effects their motor system causes. This is the case for manual actions such as pushing buttons, kicking footballs, and all acts that affect the physical environment. We ask whether initiating joint attention - causing another person to follow our eye movement - can elicit an implicit sense of agency over this congruent gaze response. Eye movements themselves cannot directly affect the physical environment, but joint attention is an example of how eye movements can indirectly cause social outcomes. Here we show that leading the gaze of an on-screen face induces an underestimation of the temporal gap between action and consequence (Experiments 1 and 2). This underestimation effect, named 'temporal binding,' is thought to be a measure of an implicit sense of agency. Experiment 3 asked whether merely making an eye movement in a non-agentic, non-social context might also affect temporal estimation, and no reliable effects were detected, implying that inconsequential oculomotor acts do not reliably affect temporal estimations under these conditions. Together, these findings suggest that an implicit sense of agency is generated when initiating joint attention interactions. This is important for understanding how humans can efficiently detect and understand the social consequences of their actions.

An evaluation of the use of short message service during an avian influenza outbreak on a poultry farm in Young.

In 2013 an avian influenza outbreak occurred in a large poultry farm in Young (approximately 2 hours north-west of Canberra.) The responsible strain was H7N2, which is highly pathogenic and can affect humans. Daily surveillance was required for those individuals who were possibly exposed. This was conducted through the use of daily message through the short message service (SMS). A total of 55 people were identified as having had high risk exposure and requiring monitoring during the surveillance period from 16 to 25 October 2013. A SMS message was sent daily to each contact within 2 groups. (Group 1 were contacts who agreed to take Tamiflu prophylaxis, and Group 2 were contacts who were under surveillance but declined Tamiflu prophylaxis). The average daily response rate for SMS was 66% (median 75%) over a 9 day period. Of those who nominated to receive the daily SMS 98% confirmed they'd received the SMS and it reminded them to take their Tamiflu medication. The public health unit (PHU) team found the use of SMS to be less time consuming than conducting telephone follow-up interviews. The PHU team believed that the use of the technology decreased the likelihood of additional staff being required to assist in the outbreak. Utilising SMS was a new initiative for the PHU and staff found it overall easy to use. These findings confirm there can be significant benefits to using SMS during a large surveillance activity. The application of SMS during this outbreak was estimated at 2.5 times more cost effective that telephone follow-ups and would substantially reduce staffing costs further in the event of a very large outbreak.

Social orienting in gaze leading: a mechanism for shared attention.

Here, we report a novel social orienting response that occurs after viewing averted gaze. We show, in three experiments, that when a person looks from one location to an object, attention then shifts towards the face of an individual who has subsequently followed the person's gaze to that same object. That is, contrary to 'gaze following', attention instead orients in the opposite direction to observed gaze and towards the gazing face. The magnitude of attentional orienting towards a face that 'follows' the participant's gaze is also associated with self-reported autism-like traits. We propose that this gaze leading phenomenon implies the existence of a mechanism in the human social cognitive system for detecting when one's gaze has been followed, in order to establish 'shared attention' and maintain the ongoing interaction.

Diagnosis of treponemal co-infection in HIV-infected West Africans.

OBJECTIVES: To evaluate the performance of two enzyme immunoassays (EIA), Murex and ICE, and the Determine TP point-of-care test (POCT) in diagnosing treponemal infection (syphilis or yaws) in patients attending a large HIV clinic in Ghana; to determine the prevalence of treponemal co-infections; and to characterise demographic and clinical features of patients with infection. METHODS: Samples were tested with EIAs and rapid plasma reagin (RPR), then POCT and reference assays for Treponema pallidum to determine prevalence of active and past infection. Sensitivity and specificity of each assay were calculated and demographic and clinical characteristics of patients compared. Data were collected from case notes of patients retrospectively. RESULTS: Overall, 45/284 patient samples (14.8%, 95% CI, 11.1-19.4%) were Treponema pallidum particle agglutination (TPPA) positive, and of these, 27 (64.3%) were RPR positive and 4 (8.9%) were treponemal IgM positive. Both EIAs and Determine TP POCT showed high sensitivities and specificities for identifying infection although RPR was less reliable. Clinical features of syphilis or yaws were rarely identified in TPPA-positive patients suggesting most had previous or late latent infection. Treatment of various intercurrent infections using short courses of antibiotics active against T. pallidum was common in the clinic. CONCLUSIONS: A high proportion of this HIV-infected cohort showed evidence of treponemal infection. Both EIAs as well as the POCT were practical and effective at diagnosing treponemal co-infection in this setting. RPR alone was unreliable at identifying active treponemal co-infection, however might be useful in some settings where treponemal-specific assays are unaffordable.

Immunisation of the equine uterus against Streptococcus equi subspecies zooepidemicus using an intranasal attenuated Salmonella vector.

Attenuated Salmonella enterica serovar Typhimurium MGN707, expressing the SzP protective protein of the MB9 serovar of Streptococcus equi subspecies zooepidemicus (SzP-MB9) was tested for its safety and efficacy as a nebulised intranasal vaccine against streptococcal uterine infections in mares. In a preliminary study, vaccinated mares (n=5) displayed serum, nasal and uterine responses (P<0.05) to S. Typhimurium lipopolysaccharide (St-LPS). Subsequently, vaccinated mares (expressor group, n=7), but not mares vaccinated with the vector only (control group, n=7), displayed significant increases in SzP-MB9 antibodies in serum, nasal and uterine washes (P<0.05). Assuming the uteri of all nine mares were free of streptococci prior to challenge with 6.3 x 10(9) colony forming units of S. e. zooepidemicus MB9, significantly fewer S. e. zooepidemicus were cultured from the uterine flushings of expressor-vaccinated mares (n=4) compared to control-vaccinated mares (n=5) (P<0.001). The only adverse reaction to vaccination was nasal haemorrhage in one mare.

Identification and functional characterization of the human glutathione S-transferase P1 gene as a novel transcriptional target of the p53 tumor suppressor gene.

The glutathione S-transferase P1 (GSTP1) is involved in multiple cellular functions, including phase II metabolism, stress response, signaling, and apoptosis. The mechanisms underlying the significantly high GSTP1 expression in many human tumors are, however, currently not well understood. We report here that the GSTP1 gene is a heretofore unrecognized downstream transcriptional target of the tumor suppressor p53. We identified a p53-binding motif comprising two consecutive half-sites located in intron 4 of the GSTP1 gene and is highly homologous to consensus p53-binding motifs in other p53-responsive genes. Using a combination of electrophoretic mobility shift assay and DNase I footprinting analyses, we showed that wild-type p53 protein binds to the GSTP1 p53 motif and luciferase reporter assays showed the motif to be transcriptionally functional in human tumor cells. In a temperature-sensitive p53-mutant cells, levels of both p21/WAF1 and GSTP1 gene transcripts increased time dependently when cells were switched from the inactive mutant state to the wild-type p53 state. Small interfering RNA-mediated reduction of p53 expression resulted in a specific decrease in GSTP1 expression and in tumor cells with mutated p53; adenovirally mediated expression of wild-type p53 increased GSTP1 expression significantly. In a panel of early-passage brain tumor cultures from patients, high levels of GSTP1 transcripts and protein were associated with wild-type p53 and, conversely, low GSTP1 levels with mutant p53. p53 expression knockdown by small interfering RNA increased cisplatin sensitivity. The ability of wild-type p53 to transcriptionally activate the human GSTP1 gene defines a novel mechanism of protecting the genome and, potentially, of tumor drug resistance.

Resolution of obstructive sleep apnea with epilepsy surgery? Expanding the relationship between sleep and epilepsy.

Recent studies suggest a higher than expected prevalence of obstructive sleep apnea (OSA) in patients with refractory epilepsy. In some cases, treatment of OSA improves seizure control. We report a case in which clinically significant OSA disappeared after left frontal lobe resection that produced a near seizure free state. This occurred in the absence of the usual factors, such as weight or medication change or variation in polysomnography (PSG) recording methodology, that often confound the comparison of sequential PSGs over time. Our patient underwent PSG with 18-channel EEG recording pre- and postoperatively using standardized scoring techniques. Baseline testing revealed an apnea-hypopnea index (AHI) of 24 with severe oxygen desaturations reaching a nadir of 62%. Postoperative testing found both the AHI and oxygen saturation normalized as well as a marked reduction in spike rate. We hypothesize that the pathophysiology of OSA in patients with epilepsy may be impacted by frequent, extensive interictal epileptiform discharges (IEDs) and/or seizures altering upper airway control during sleep.

The equine immune response to Streptococcus equi subspecies zooepidemicus during uterine infection.

The purpose of this study was to describe strain-specific immune responses to Streptococcus equi subspecies zooepidemicus (S. zooepidemicus) during uterine infection in horses. Five isolates of S. zooepidemicus were differentiated into four strains antigenically by bactericidal testing in blood of 12 horses, and genetically by pulsed-field gel electrophoresis. Eight healthy mares were then divided into two groups, each inoculated with one strain intrauterinely on three successive oestrous cycles followed by a second strain for three successive cycles, first and second strains being reversed for each group. Immune responses to both strains were assessed by bactericidal testing and immunoblotting over eight cycles. Both techniques indicated that immune responses to each strain arose at different times. Immunoblots showed greater binding to the first inoculated strain than to the second (P < 0.05). These data confirm that immune responses to S. zooepidemicus during uterine infection are partly strain-specific.

Effects of orthographic and phonological word length on memory for lists shown at RSVP and STM rates.

This article reports 3 experiments in which effects of orthographic and phonological word length on memory were examined for short lists shown at rapid serial visual presentation (RSVP) and short-term memory (STM) rates. Only visual-orthographic length reduced RSVP serial recall, whereas both orthographic and phonological length lowered recall for STM lists in Experiment 1. Word-length effects may arise from output processes or from the temporal duration of output in recall. In 2 further experiments, output demands were reduced through the use of a recognition test. Recognition accuracy was impaired only by orthographic length for RSVP lists and by phonological length for STM lists in both experiments. The results demonstrate 2 item length effects not simply attributable to increased output time in recall, and implications for theories of STM are considered.

Cigarette smoking, glutathione-s-transferase M1 and t1 genetic polymorphisms, and breast cancer risk (United States).

OBJECTIVE: It has been suggested that functional polymorphisms in genes encoding tobacco carcinogen-metabolizing enzymes may modify the relationship between tobacco smoking and breast cancer risk. We sought to determine if there is a gene-environment interaction between GSTM I (GSTM1A and GSTM1B), and GSTT1 genotypes and cigarette smoking in the risk of breast cancer. METHODS: Cases and controls were recruited in a case-control study conducted in Connecticut from 1994 to 1998. Cases were histologically confirmed, incident breast cancer patients, and controls were randomly selected from women histologically confirmed to be without breast cancer. A total of 338 cases and 345 controls were genotyped for GSTM1 and GSTT1 . RESULTS: None of the GSTM 1 genotypes, either alone or in combination with cigarette smoking, was associated with breast cancer risk. There was, however, a significantly increased risk of breast cancer among postmenopausal women with a GSTTI null genotype (OR= 1.9, 95% CI 1.2-2.9). There were also indications of increased risk of breast cancer associated with cigarette smoking for postmenopausal women with GSTT1-null genotype, especially for those who commenced smoking before age 18 (OR = 2.9, 95% CI 1.0-8.8). CONCLUSION: Women with a GSTT1-null genotype may have an increased breast cancer risk, especially postmenopausal women who started smoking at younger ages.