Investigating the clinical advantages of a robotic linac equipped with a multileaf collimator in the treatment of brain and prostate cancer patients.

The purpose of this study was to evaluate the performance of a commercially available CyberKnife system with a multileaf collimator (CK-MLC) for stereotactic body radiotherapy (SBRT) and standard fractionated intensity-modulated radiotherapy (IMRT) applications. Ten prostate and ten intracranial cases were planned for the CK-MLC. Half of these cases were compared with clinically approved SBRT plans generated for the CyberKnife with circular collimators, and the other half were compared with clinically approved standard fractionated IMRT plans generated for conventional linacs. The plans were compared on target coverage, conformity, homogeneity, dose to organs at risk (OAR), low dose to the surrounding tissue, total monitor units (MU), and treatment time. CK-MLC plans generated for the SBRT cases achieved more homogeneous dose to the target than the CK plans with the circular collimators, for equivalent coverage, conformity, and dose to OARs. Total monitor units were reduced by 40% to 70% and treatment time was reduced by half. The CK-MLC plans generated for the standard fractionated cases achieved prescription isodose lines between 86% and 93%, which was 2%-3% below the plans generated for conventional linacs. Compared to standard IMRT plans, the total MU were up to three times greater for the prostate (whole pelvis) plans and up to 1.4 times greater for the intracranial plans. Average treatment time was 25 min for the whole pelvis plans and 19 min for the intracranial cases. The CK-MLC system provides significant improvements in treatment time and target homogeneity compared to the CK system with circular collimators, while maintaining high conformity and dose sparing to critical organs. Standard fractionated plans for large target volumes (>100 cm3) were generated that achieved high prescription isodose levels. The CK-MLC system provides more efficient SRS and SBRT treatments and, in select clinical cases, might be a potential alternative for standard fractionated treatments. PACS numbers: 87.56.nk, 87.56.bd

LGN plays distinct roles in oral epithelial stratification, filiform papilla morphogenesis and hair follicle development

Oral epithelia protect against constant challenges by bacteria, viruses, toxins and injury while also contributing to the formation of ectodermal appendages such as teeth, salivary glands and lingual papillae. Despite increasing evidence that differentiation pathway genes are frequently mutated in oral cancers, comparatively little is known about the mechanisms that regulate normal oral epithelial development. Here, we characterize oral epithelial stratification and describe multiple distinct functions for the mitotic spindle orientation gene LGN (Gpsm2) in promoting differentiation and tissue patterning in the mouse oral cavity. Similar to its function in epidermis, apically localized LGN directs perpendicular divisions that promote stratification of the palatal, buccogingival and ventral tongue epithelia. Surprisingly, however, in dorsal tongue LGN is predominantly localized basally, circumferentially or bilaterally and promotes planar divisions. Loss of LGN disrupts the organization and morphogenesis of filiform papillae but appears to be dispensable for embryonic hair follicle development. Thus, LGN has crucial tissue-specific functions in patterning surface ectoderm and its appendages by controlling division orientation

Opportunities for refinement in neuroscience: Indicators of wellness and post-operative pain in laboratory macaques

Being able to assess pain in nonhuman primates undergoing biomedical procedures is important for preventing and alleviating pain, and for developing better guidelines to minimise the impacts of research on welfare in line with the 3Rs principle of Refinement. Nonhuman primates are routinely used biomedical models however it remains challenging to recognise negative states, including pain, in these animals. This study aimed to identify behavioural and facial changes that could be used as pain or general wellness indicators in the rhesus macaque (Macaca mulatta). Thirty-six macaques scheduled for planned neuroscience procedures were opportunistically monitored at four times: Pre-Operative (PreOp), Post-Operative (PostOp) once the effects of anaesthesia had dissipated, Pre-Analgesia (PreAn) on the subsequent morning prior to repeating routine analgesic treatment, and Post-Analgesia (PostAn) following administration of analgesia. Pain states were expected to be absent in PreOp, moderate in PreAn, and mild or absent in PostOp and PostAn when analgesia had been administered. Three potential pain indicators were identified: lip tightening and chewing, which were most likely to occur in PreAn, and running which was least likely in PreAn. Arboreal behaviour indicated general wellness, while half-closed eyes, leaning of the head or body shaking indicated the opposite. Despite considerable individual variation, behaviour and facial expressions could offer important indicators of pain and wellness and should be routinely quantified, and appropriate interventions applied to prevent or alleviate pain, and promote positive welfare

Performance of HPGe Detectors in High Magnetic Fields

A new generation of high-resolution hypernuclear gamma$-spectroscopy experiments with high-purity germanium detectors (HPGe) are presently designed at the FINUDA spectrometer at DAPhiNE, the Frascati phi-factory, and at PANDA, the antiproton proton hadron spectrometer at the future FAIR facility. Both, the FINUDA and PANDA spectrometers are built around the target region covering a large solid angle. To maximise the detection efficiency the HPGe detectors have to be located near the target, and therefore they have to be operated in strong magnetic fields B ~ 1 T. The performance of HPGe detectors in such an environment has not been well investigated so far. In the present work VEGA and EUROBALL Cluster HPGe detectors were tested in the field provided by the ALADiN magnet at GSI. No significant degradation of the energy resolution was found, and a change in the rise time distribution of the pulses from preamplifiers was observed. A correlation between rise time and pulse height was observed and is used to correct the measured energy, recovering the energy resolution almost completely. Moreover, no problems in the electronics due to the magnetic field were observed.Comment: submitted to Nucl. Instrum. Meth. Phys. Res. A, LaTeX, 19 pages, 9 figure

AGS3 antagonizes LGN to balance oriented cell divisions and cell fate choices in mammalian epidermis

Oriented cell divisions balance self-renewal and differentiation in stratified epithelia such as the skin epidermis. During peak epidermal stratification, the distribution of division angles among basal keratinocyte progenitors is bimodal, with planar and perpendicular divisions driving symmetric and asymmetric daughter cell fates, respectively. An apically restricted, evolutionarily conserved spindle orientation complex that includes the scaffolding protein LGN/Pins/Gpsm2 plays a central role in promoting perpendicular divisions and stratification, but why only a subset of cell polarize LGN is not known. Here, we demonstrate that the LGN paralog, AGS3/Gpsm1, is a novel negative regulator of LGN and inhibits perpendicular divisions. Static and ex vivo live imaging reveal that AGS3 overexpression displaces LGN from the apical cortex and increases planar orientations, while AGS3 loss prolongs cortical LGN localization and leads to a perpendicular orientation bias. Genetic epistasis experiments in double mutants confirm that AGS3 operates through LGN. Finally, clonal lineage tracing shows that LGN and AGS3 promote asymmetric and symmetric fates, respectively, while also influencing differentiation through delamination. Collectively, these studies shed new light on how spindle orientation influences epidermal stratification

Auditory laterality in a nocturnal, fossorial marsupial (Lasiorhinus latifrons) in response to bilateral stimuli

Behavioural lateralisation is evident across most animal taxa, although few marsupial and no fossorial species have been studied. Twelve wombats (Lasiorhinus latifrons) were bilaterally presented with eight sounds from different contexts (threat, neutral, food) to test for auditory laterality. Head turns were recorded prior to and immediately following sound presentation. Behaviour was recorded for 150 seconds after presentation. Although sound differentiation was evident by the amount of exploration, vigilance and grooming performed after different sound types, this did not result in different patterns of head turn direction. Similarly, left-right proportions of head turns, walking events and food approaches in the post-sound period were comparable across sound types. A comparison of head turns performed before and after sound showed a significant change in turn direction (χ2 1 = 10.65, P = 0.001) from a left preference during the pre-sound period (mean 58% left head turns, CI 49-66%) to a right preference in the post-sound (mean 43% left head turns, CI 40-45%). This provides evidence of a right auditory bias in response to the presentation of the sound. This study therefore demonstrates that laterality is evident in southern hairy-nosed wombats in response to a sound stimulus, although side biases were not altered by sounds of varying context

A hybrid radiation detector for simultaneous spatial and temporal dosimetry

In this feasibility study an organic plastic scintillator is calibrated against ionisation chamber measurements and then embedded in a polymer gel dosimeter to obtain a quasi-4D experimental measurement of a radiation field. This hybrid dosimeter was irradiated with a linear accelerator, with temporal measurements of the dose rate being acquired by the scintillator and spatial measurements acquired with the gel dosimeter. The detectors employed in this work are radiologically equivalent; and we show that neither detector perturbs the intensity of the radiation field of the other. By employing these detectors in concert, spatial and temporal variations in the radiation intensity can now be detected and gel dosimeters can be calibrated for absolute dose from a single irradiation

Risk of Hospitalization and Death for COVID-19 in People with Parkinson's Disease or Parkinsonism

The risk of COVID-19 and related death in people with Parkinson's disease or parkinsonism is uncertain. The aim of the study was to assess the risk of hospitalization for COVID-19 and death in a cohort of patients with Parkinson's disease or parkinsonism compared with a control population cohort, during the epidemic bout (March-May 2020) in Bologna, northern Italy