Multiple peripheral pneumococcal mycotic aneurysms without aortic involvement: A unique case confirmed with the novel use of a molecular diagnostic technique

Mycotic aneurysms confer a high morbidity and mortality. Streptococcus pneumoniae aneurysms usually affect the aorta and are rare, although bacterial cultures from aneurysm tissue may be difficult following prior antimicrobial therapy. We report a unique case of mycotic femoral and popliteal artery aneurysms following pneumococcal pneumonia and meningitis, which were managed by resection, revascularization with autologous vein, and intravenous benzylpenicillin. Although blood and aneurysm sac cultures were negative, arterial wall S pneumoniae DNA was detected by polymerase chain reaction (PCR). Appropriate molecular diagnostic techniques can facilitate diagnosis and direct antimicrobial therapy; an important consideration with increasing antimicrobial resistance

Technique of fuzzy tuned stochastic scanpaths for robot vision

The real-time processing of frame sequences obtained from cameras mounted on autonomous mobile robots and vehicles is a computationally intensive task. This paper is a review of the work carried out so far in the development of a procedure using fuzzy-tuned stochastic 'scanpaths' for efficiently scanning images in a frame sequence. A concise explanation of using fuzzy-tuned stochastic scanpaths is given here followed by a summary of the experimental work that has been undertaken to date and results achieved. The results show how the technique can reliably locate objects in scene whilst examining only a fraction of the image surface, e.g. 5%. The paper concludes with a discussion on research insofar accomplished and proposes ideas for future work

GALA: an international multicentre randomised trial comparing general anaesthesia versus local anaesthesia for carotid surgery

Background: Patients who have severe narrowing at or near the origin of the internal carotid artery as a result of atherosclerosis have a high risk of ischaemic stroke ipsilateral to the arterial lesion. Previous trials have shown that carotid endarterectomy improves long-term outcomes, particularly when performed soon after a prior transient ischaemic attack or mild ischaemic stroke. However, complications may occur during or soon after surgery, the most serious of which is stroke, which can be fatal. It has been suggested that performing the operation under local anaesthesia, rather than general anaesthesia, may be safer. Therefore, a prospective, randomised trial of local versus general anaesthesia for carotid endarterectomy was proposed to determine whether type of anaesthesia influences peri-operative morbidity and mortality, quality of life and longer term outcome in terms of stroke-free survival. Methods/design: A two-arm, parallel group, multicentre randomised controlled trial with a recruitment target of 5000 patients. For entry into the study, in the opinion of the responsible clinician, the patient requiring an endarterectomy must be suitable for either local or general anaesthesia, and have no clear indication for either type. All patients with symptomatic or asymptomatic internal carotid stenosis for whom open surgery is advised are eligible. There is no upper age limit. Exclusion criteria are: no informed consent; definite preference for local or general anaesthetic by the clinician or patient; patient unlikely to be able to co-operate with awake testing during local anaesthesia; patient requiring simultaneous bilateral carotid endarterectomy; carotid endarterectomy combined with another operation such as coronary bypass surgery; and, the patient has been randomised into the trial previously. Patients are randomised to local or general anaesthesia by the central trial office. The primary outcome is the proportion of patients alive, stroke free ( including retinal infarction) and without myocardial infarction 30 days post-surgery. Secondary outcomes include the proportion of patients alive and stroke free at one year; health related quality of life at 30 days; surgical adverse events, re-operation and re-admission rates; the relative cost of the two methods of anaesthesia; length of stay and intensive and high dependency bed occupancy

Tropical ancient DNA from bulk archaeological fish bone reveals the subsistence practices of a historic coastal community in southwest Madagascar

Taxonomic identification of archaeological fish bones provides important insights into the subsistence practices of ancient coastal peoples. However, it can be difficult to execute robust morphological identification of fish bones from species-rich fossil assemblages, especially from post-cranial material with few distinguishing features. Fragmentation, weathering and burning further impede taxonomic identification, resulting in large numbers of unidentifiable bones from archaeological sites. This limitation can be somewhat mitigated by taking an ancient DNA (aDNA) bulk-bone metabarcoding (BBM) approach to faunal identification, where DNA from non-diagnostic bone fragments is extracted and sequenced in parallel. However, a large proportion of fishing communities (both past and present) live in tropical regions that have sub-optimal conditions for long-term aDNA preservation. To date, the BBM method has never been applied to fish bones before, or to fossils excavated from an exposed context within a tropical climate. Here, we demonstrate that morphologically indistinct bulk fish bone from the tropics can be identified by sequencing aDNA extracted from 100 to 300 ya archaeological midden material in southwest Madagascar. Despite the biases of the approach, we rapidly obtained family, genus, and species-level assemblage information, and used this to describe a subset of the ichthyofauna exploited by an 18th century fishing community. We identified 23 families of fish, including benthic, pelagic, and coral-dwelling fishes, suggesting a reliance on a variety of marine and brackish habitats. When possible, BBM should be used alongside osteological approaches to address the limitations of both; however, this study highlights how genetic methods can nevertheless be a valuable tool for helping resolve faunal assemblages when morphological identification is hindered by taphonomic processes, lack of adequate comparative collections, and time constraints, and can provide a temporal perspective on fish biodiversity in the context of accelerated exploitation of the marine environment

Timing of PD-1 Blockade Is Critical to Effective Combination Immunotherapy with Anti-OX40.

Purpose: Antibodies specific for inhibitory checkpoints PD-1 and CTLA-4 have shown impressive results against solid tumors. This has fueled interest in novel immunotherapy combinations to affect patients who remain refractory to checkpoint blockade monotherapy. However, how to optimally combine checkpoint blockade with agents targeting T-cell costimulatory receptors, such as OX40, remains a critical question.Experimental Design: We utilized an anti-PD-1-refractory, orthotopically transplanted MMTV-PyMT mammary cancer model to investigate the antitumor effect of an agonist anti-OX40 antibody combined with anti-PD-1. As PD-1 naturally aids in immune contraction after T-cell activation, we treated mice with concurrent combination treatment versus sequentially administering anti-OX40 followed by anti-PD-1.Results: The concurrent addition of anti-PD-1 significantly attenuated the therapeutic effect of anti-OX40 alone. Combination-treated mice had considerable increases in type I and type II serum cytokines and significantly augmented expression of inhibitory receptors or exhaustion markers CTLA-4 and TIM-3 on T cells. Combination treatment increased intratumoral CD4+ T-cell proliferation at day 13, but at day 19, both CD4+ and CD8+ T-cell proliferation was significantly reduced compared with untreated mice. In two tumor models, sequential combination of anti-OX40 followed by anti-PD-1 (but not the reverse order) resulted in significant increases in therapeutic efficacy. Against MMTV-PyMT tumors, sequential combination was dependent on both CD4+ and CD8+ T cells and completely regressed tumors in approximately 30% of treated animals.Conclusions: These results highlight the importance of timing for optimized therapeutic effect with combination immunotherapies and suggest the testing of sequencing in combination immunotherapy clinical trials. Clin Cancer Res; 23(20); 6165-77. ©2017 AACRSee related commentary by Colombo, p. 5999

Neuroinflammatory and cognitive consequences of combined radiation and immunotherapy in a novel preclinical model.

BACKGROUND: Cancer patients often report behavioral and cognitive changes following cancer treatment. These effects can be seen in patients who have not yet received treatment or have received only peripheral (non-brain) irradiation. Novel treatments combining radiotherapy (RT) and immunotherapy (IT) demonstrate remarkable efficacy with respect to tumor outcomes by enhancing the proinflammatory environment in the tumor. However, a proinflammatory environment in the brain mediates cognitive impairments in other neurological disorders and may affect brain function in cancer patients receiving these novel treatments. Currently, gaps exist as to whether these treatments impact the brain in individuals with or without tumors and with regard to the underlying mechanisms. RESULTS: Combined treatment with precision RT and checkpoint inhibitor IT achieved control of tumor growth. However, BALB/c mice receiving combined treatment demonstrated changes in measures of anxiety levels, regardless of tumor status. C57BL/6J mice with tumors demonstrated increased anxiety, except following combined treatment. Object recognition memory was impaired in C57BL/6J mice without tumors following combined treatment. All mice with tumors showed impaired object recognition, except those treated with RT alone. Mice with tumors demonstrated impaired amygdala-dependent cued fear memory, while maintaining hippocampus-dependent context fear memory. These behavioral alterations and cognitive impairments were accompanied by increased microglial activation in mice receiving immunotherapy alone or combined with RT. Finally, based on tumor status, there were significant changes in proinflammatory cytokines (IFN-γ, IL-6, IL-5, IL-2, IL-10) and a growth factor (FGF-basic). MATERIALS AND METHODS: Here we test the hypothesis that IT combined with peripheral RT have detrimental behavioral and cognitive effects as a result of an enhanced proinflammatory environment in the brain. BALB/c mice with or without injected hind flank CT26 colorectal carcinoma or C57BL/6J mice with or without Lewis Lung carcinoma were used for all experiments. Checkpoint inhibitor IT, using an anti-CTLA-4 antibody, and precision CT-guided peripheral RT alone and combined were used to closely model clinical treatment. We assessed behavioral and cognitive performance and investigated the immune environment using immunohistochemistry and multiplex assays to analyze proinflammatory mediators. CONCLUSIONS: Although combined treatment achieved tumor growth control, it affected the brain and induced changes in measures of anxiety, cognitive impairments, and neuroinflammation

The effectiveness of Ultrasound guided Hydrodistension and physiotherapy in the treatment of Frozen shoulder/Adhesive Capsulitis in Primary Care: a single centre service evaluation

Background: Evidence for optimal non-operative treatment of frozen shoulder is lacking. The aim of this study is to evaluate a treatment strategy for stage II-III Frozen shoulder provided by the current primary care Musculoskeletal Service. Methods: GP referrals of shoulder pain to the musculoskeletal service diagnosed with stage II-III frozen shoulder and who opted for a treatment strategy of hydrodistension and guided physiotherapy exercise programme over a 12 month period were evaluated for 6 months. Thirty three patients were diagnosed with stage II-III frozen shoulder by specialist physiotherapists and opted for the treatment strategy. Outcome measures included SPADI and QuickDASH, pain score and range of movement. Data was collected at baseline, 6 weeks, 12 weeks and 6 months. Results: All patients significantly improved in shoulder symptoms on the SPADI and QuickDASH scores (p< 0.001). Pain scores and range of shoulder movement flexion, abduction, external rotation showed significant improvement at all time points (p<0.001). Conclusions: This service evaluation demonstrates that management of frozen shoulder stage II-III, by physiotherapists in a primary care setting utilizing hydrodistension and guided exercise programme is an effective non-operative treatment strategy. Level of evidence: Level III, Service evaluation