The maintenance of head-only minimum stunning currents for sheep to ≥ 1.0 Amp as per current legislation was examined in two trials in a commercial abattoir. In the first trial, a Jetco MS100 stunner failed to maintain the current to > 1.0 Amp in 118 of the 228 sheep. In a second trial, a Jetco MS105 delivered sufficient current in all sheep (n = 275) to meet the legislative requirement, apart from a single animal. Recorded electrocardiograms showed a regular heartbeat, with no evidence of ventricular fibrillation, in all animals in both trials following stunning and neck-cut. Only one of the two stun units may therefore be considered to meet the statutory requirements but both may meet the requirements for halal slaughter where pre-stun is considered acceptable.

In Canada, the 2014 Code of Practice for the Care and Handling of Pigs proposed the continued operation of existing stall barns after 2024 on condition that bred sows be given access to periodic exercise. Therefore, this study evaluated the effects of periodic exercise on sow welfare. Sows (n = 180) were assigned to one of three treatments: stall-housed (Control: C); stall-housed and exercised weekly for 10 min (Exercise: E); and group-housed (Group: G). Sow postures and stereotypies were recorded once per week in early, mid and late gestation before (AM) and after (PM) exercise. Female piglets (n = 168 from C, E and G sows) underwent isolation and novel object tests at 19-22 days of age. Postures differed by treatment in AM with G sows lying more and sitting less than C and E sows, which did not differ. In PM, E sows sat more than G sows, with C sows being intermediate. In early gestation, G sows performed fewer stereotypies than E sows, with C sows being intermediate. In mid gestation, G sows performed fewer stereotypies than C and E sows, which did not differ. Piglets from C sows were more active in the novel object test than E and G piglets, which did not differ. Group housing improved sow comfort (indicated by postures) and reduced sow stress (indicated by stereotypies), but periodic exercise did not. Decreased activity level in piglets from sows given greater freedom of movement indicates that gestation housing can influence the behaviour of offspring.

Current standard-of-care for glioblastoma (GBM) includes surgery, radiation and temozolomide. Most tumors recur within a year from diagnosis and median survival for recurrent GBM (rGBM) is 3-9 months. Unmethylated promoter status for O6-methylguanine-DNA-methyltransferase (MGMT) is a validated biomarker for temozolomide-resistance, exhibited by most GBM patients. VAL-083 is a DNA-targeting agent with a mechanism-of-action that is independent of MGMT. VAL-083 overcomes temozolomide-resistance in GBM cell-lines, cancer stem cells, and in vivo models. VAL-083 readily crosses the blood-brain barrier and accumulates in brain-tumor tissue. We recently completed a VAL-083 dose-escalation trial in temozolomide- and bevacizumab-refractory rGBM and determined that 40mg/m2/day given intravenously on days 1,2,3 of a 21-day cycle is generally well-tolerated. This dosing regimen was selected for subsequent GBM trials, including an ongoing single-arm, biomarker-driven Phase 2 trial (N=48) in temolozomide-refractory, bevacizumab-naïve rGBM , MGMT-unmethylated (Clinicaltrials.gov:NCT02717962). The primary objective of this study is to determine if VAL-083 improves OS compared to a historical control of 7.15 months for MGMT-unmethylated rGBM patients treated with lomustine (EORTC26101). In addition, another single-arm, biomarker-driven, Phase 2 study (N=25) of VAL-083 in combination with radiotherapy in newly diagnosed GBM, MGMT-unmethylated is ongoing (Clinicaltrials.gov:NCT03050736). This trial aims to determine a dose for further study of VAL-083 in combination with radiotherapy and explore if VAL-083 improves PFS and OS compared to historical results in newly diagnosed GBM. Enrollment and safety data updates will be provided at the meeting. The results of these studies, if successful, may support VAL-083 as part of a new chemotherapeutic treatment paradigm for GBM.

Standard-of-care for glioblastoma (GBM) includes surgery, radiation and temozolomide. Nearly all tumors recur and 5-year survival is less than 3%. Unmethylated promoter status O6-methylguanine-DNA-methyltransferase (MGMT) is a validated biomarker for temozolomide-resistance. Second-line treatment with bevacizumab has not only failed to improve survival, but has also been shown to induce intratumor hypoxia and increased chemoresistance. VAL-083 is a bi-functional DNA-targeting agent that readily crosses the blood-brain barrier. VAL-083 targets N7-guanine, causing DNA double-strand breaks and cancer cell-death in GBM cancer stem cells (CSCs) and non-CSCs, independent of MGMT. To investigate the in vivo anti-tumor effect of VAL-083+bevacizumab, we used an orthotopic GBM T16 PDX model. All mice carried MGMT-unmethylated, temozolomide-resistant recurrent GBM tumors detected by MRI 35 days post-implantation. Tumor progression was measured by MRI on days 49 and 56, and was calculated for the entire study (day 35 vs. 56) and for the last 7 days (day 49 vs. 56). Mice were grouped into control, bevacizumab, VAL-083, and VAL-083+bevacizmab. VAL-083 treatment started 3 days after bevacizumab treatment to ensure induction of hypoxia. Results: Tumors were significantly smaller in VAL-083-treated mice both compared to control (-83%, p<0.001) and compared to bevacizumab-treated (-75%, p<0.001) mice. Additionally, analysis of tumor growth in-time showed significantly reduced tumor progression for VAL-083+bevacizumab compared to VAL-083 alone (p<0.01). Conclusions: These results show strong in vivo anti-tumor efficacy of VAL-083 against MGMT-unmethylated, recurrent GBM. This effect was further augmented in combination with bevacizumab, providing rationale of clinical investigation of VAL-083+bevacizumab in GBM.

Extended abstract of a paper presented at Microscopy and Microanalysis 2010 in Portland, Oregon, USA, August 1 – August 5, 2010.

Extended abstract of a paper presented at Microscopy and Microanalysis 2009 in Richmond, Virginia, USA, July 26 – July 30, 2009

Extended abstract of a paper presented at Microscopy and Microanalysis 2007 in Ft. Lauderdale, Florida, USA, August 5 – August 9, 2007

Extended abstract of a paper presented at Microscopy and Microanalysis 2006 in Chicago, Illinois, USA, July 30 – August 3, 2006

Identical female twins (age 11 years) with congenital ocular motor apraxia and generalized idiopathic epilepsy are reported. Their presenting symptoms were a long history of abnormal head and eye movements. One twin developed partial sensory seizures. The patients underwent 16-channel EEG, electro-oculographic recordings, MRI of the brain, and genetic and metabolic investigations. EEG findings were consistent with idiopathic generalized epilepsy. Electro-oculographic recordings of the saccades confirmed an inability to elicit horizontal saccades without preceding head movement; saccades to the left were better than saccades to the right. MR scans for one twin showed normal findings, however, for the twin who had meningitis they revealed asymmetry between the right and left temporal lobes but no specific abnormality. DNA analysis using a series of autosomal polymorphic markers confirmed the monozygocity of the twins. White blood cell enzyme analysis excluded Sandhoff disease, Tay–Sachs disease, GM1 gangliosidosis, metacromatic leucodystrophy, Gaucher disease, Niemann-Pick disease (A and B), and Krabbe leucodystrophy. Albumin and immunoglobulin (IgA, IgG, and IgM) levels were normal. It is concluded that autosomal recessive inheritance seems the most likely explanation here, as recent studies have found insertion and missense mutations of the aprataxin gene which have been related to an early onset form of ataxia with ocular motor apraxia and hypoalbuminaemia.

GaN layers periodically-doped with arsenic were grown by plasma-assisted molecular beam epitaxy on sapphire substrates. Secondary ion mass spectroscopy studies using different secondary ions clearly confirmed the existence of As-modulation in the GaN/GaN:As periodically-doped structures, however, the degree of As-modulation is still under discussion. The use of modulation doping with As has a strong influence on the optical properties of GaN/GaN:As structures.