Attenuated responses to attention-modulating drugs in the neuroligin-3R451C mouse model of autism.

Attention deficits are frequently reported within the clinical autism population. Despite not being a core diagnostic feature, some aetiological theories place atypical attention at the centre of autism development. Drugs used to treat attention dysfunction are therefore increasingly prescribed to autistic patients, though currently off-label with uncertain efficacy. We utilised a rodent-translated touchscreen test of sustained attention in mice carrying an autism-associated R451C mutation in the neuroligin-3 gene (Nlgn3R451C). In doing so, we replicated their cautious but accurate response profile and probed it using two widely prescribed attention-modulating drugs: methylphenidate (MPH) and atomoxetine (ATO). In wild-type mice, acute administration of MPH (3 mg/kg) promoted impulsive responding at the expense of accuracy, while ATO (3 mg/kg) broadly reduced impulsive responding. These drug effects were absent in Nlgn3R451C mice, other than a small reduction in blank touches to the screen following ATO administration. The absence of drug effects in Nlgn3R451C mice likely arises from their altered behavioural baseline and underlying neurobiology, highlighting caveats to the use of classic attention-modulating drugs across disorders and autism subsets. It further suggests that altered dopaminergic and/or norepinephrinergic systems may drive behavioural differences in the Nlgn3R451C mouse model of autism, supporting further targeted investigation.

Operationalizing a fisheries social-ecological system through a Bayesian belief network reveals hotspots for its adaptive capacity in the southern North sea.

Fisheries social-ecological systems (SES) in the North Sea region confront multifaceted challenges stemming from environmental changes, offshore wind farm expansion, and marine protected area establishment. In this paper, we demonstrate the utility of a Bayesian Belief Network (BN) approach in comprehensively capturing and assessing the intricate spatial dynamics within the German plaice-related fisheries SES. The BN integrates ecological, economic, and socio-cultural factors to generate high-resolution maps of profitability and adaptive capacity potential (ACP) as prospective management targets. Our analysis of future scenarios, delineating changes in spatial constraints, economics, and socio-cultural aspects, identifies factors that will exert significant influence on this fisheries SES in the near future. These include the loss of fishing grounds due to the installation of offshore wind farms and marine protected areas, as well as reduced plaice landings due to climate change. The identified ACP hotspots hold the potential to guide the development of localized management strategies and sustainable planning efforts by highlighting the consequences of management decisions. Our findings emphasize the need to consider detailed spatial dynamics of fisheries SES within marine spatial planning (MSP) and illustrate how this information may assist decision-makers and practitioners in area prioritization. We, therefore, propose adopting the concept of fisheries SES within broader integrated management approaches to foster sustainable development of inherently dynamic SES in a rapidly evolving marine environment.

The prevention of radiation-induced small bowel complications.

Moderate dose pelvic radiotherapy is associated with a 5% severe complication risk related to the small bowel. Strictures and/or fistulation can occur many years after treatment. These complications are difficult to treat, and surgical treatment (excision, bypass) bears a significant morbidity risk. The risk of chronic diarrhoea or malabsorption may increase to 40%, depending on the irradiated small bowel volume. Late small bowel complications are generally irreversible due to vascular aetiology. Prevention of these complications can be achieved by limiting the volume of small bowel treated. Consequences for radiotherapeutic techniques in treatment for rectal cancer are multiple beam set-up, customised blocking based on visualisation of the small bowel in the treatment position, and the use of a special open table-top device that results in a small bowel shift from the treatment field.

The volume effect in radiation-related late small bowel complications: results of a clinical study of the EORTC Radiotherapy Cooperative Group in patients treated for rectal carcinoma.

PURPOSE: The purpose of this study was to quantify the correlation between irradiated small bowel volume and late occurring small bowel complications. METHODS: Small bowel volumes in the high-dose region were measured using orthogonal barium films for 203 patients treated for rectal carcinoma with pelvic postoperative radiotherapy to 50 Gy in an EORTC multicentric study. RESULTS: The 5-year estimate of late pelvic small bowel obstruction requiring surgery was 11%. No correlation between the irradiated small bowel volume and obstruction was detected. The actuarial 5-year estimate of chronic diarrhea varied from 31% in patients with irradiated small bowel volumes below 77 cm3 to 42% in patients with volumes over 328 cm3. This correlation was significant in the univariate and multivariate analysis (p = 0.025). The type of rectal surgery significantly influenced the incidence of chronic diarrhea and malabsorption, the actuarial 5-year estimate being 49% and 26% after low anterior resection and abdominoperineal resection, respectively (p = 0.04). CONCLUSIONS: This study demonstrated that there is a volume-effect in radiation-induced diarrhea at a dose of 50 Gy in 25 fractions. No volume-effect for small bowel obstruction was detected at this dose-level in pelvic postoperative radiotherapy. A review of the literature data on small bowel obstruction indicates that the volume effect at this dose level can only be demonstrated in patients who were treated with extended field radiotherapy (estimated small bowel volume 800 cm3) after intra-abdominal surgery.

Results of radiotherapy in patients with stage I orbital non-Hodgkin's lymphoma.

This paper describes the results of radiotherapy in early stage orbital non-Hodgkin's lymphoma. From 1970 to 1985, 33 orbital localizations in 30 patients were treated. The total dose applied ranged from 21 to 57 Gy (2 Gy per fraction), two-thirds of all patients received a dose of 40 Gy. The complete-response rate was 94% and the 10 years actuarial survival was 90%; no significant difference in survival was observed between patients with low grade or intermediate grade lymphoma. No local recurrence was detected during follow up and 20% of the patients developed generalized disease. Two optic nerve neuropathies and three retinopathies were observed in five patients, four of these occurred at a dose level of less than 43 Gy. Keratitis occurred in 58% of the patients treated, a sicca syndrome in 30% and cataract of different grades in 58% of the patients treated. Although local control was excellent, severe complications were observed in 13% of the patients who received a dose of less than 43 Gy.

Dose-volume correlation in radiation-related late small-bowel complications: a clinical study.

The effects of the volume of irradiated small bowel on late small-bowel tolerance was studied, taking into account the equivalent total dose and type of pre-irradiation surgical procedure. A method was developed to estimate small-bowel volumes in the high-dose region of the radiation treatment using CT-scans in the treatment position. Using this method small-bowel volumes were measured for three-field and AP-PA pelvic treatments (165 cm3 and 400 cm3, respectively), extended AP-PA pelvic treatment (790 cm3), AP-PA treatment of para-aortic nodes (550 cm3) and AP-PA treatment of para-aortic and iliac nodes (1000 cm3). In a retrospective study of 111 patients irradiated after surgery for rectal or recto-sigmoid cancer to a dose of 45-50 Gy in 5 weeks, extended AP-PA pelvic treatment (n = 27) resulted in a high incidence of severe small-bowel complications (37%), whereas for limited (three-field) pelvic treatment (n = 84) the complication rate was 6%. These complication data together with data from the literature on postoperative radiation-related small-bowel complications were analysed using the maximum likelihood method to fit the data to the logistic form of the dose-response relation, taking the volume effect into account by a power law. The analysis indicated that the incidence of radiation-related small-bowel complications was higher after rectal surgery than after other types of surgery, which might be explained by the development of more adhesions. For both types of surgery a volume exponent of the power-law of 0.26 +/- 0.05 was established. This means that if the small-bowel volume is increased by a factor of 2, the total dose has to be reduced by 17% for the same incidence of small-bowel complications.