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Background Randomized studies have shown low compliance to adjuvant chemotherapy in rectal cancer patients receiving preoperative chemotherapy and external beam radiation (CT/EBRT) with total mesorectal excision. We hypothesize that giving neoadjuvant CT before local treatment would improve CT compliance. Methods Between 2010–2017, 180 patients were randomized (2:1) to either Arm A (AA) with FOLFOX x6 cycles prior to high dose rate brachytherapy (HDRBT) and surgery plus adjuvant FOLFOX x6 cycles, or Arm B (AB), with neoadjuvant HDRBT with surgery and adjuvant FOLFOX x12 cycles. The primary endpoint was CT compliance to ≥85% of full-dose CT for the first six cycles. Secondary endpoints were ypT0N0, five-year disease free survival (DFS), local control and overall survival (OS). Results Patients were randomized to either AA (n = 120, median age (MA) 62 years) or AB (n = 60, MA 63 years). 175/180 patients completed HDRBT as planned (97.2%). In AA, two patients expired during CT; three patients post-randomization received short course EBRT because of progression under CT (n = 2, AA) or personal preference (n = 1, AB). ypT0N0 was 31% in AA and 28% in AB (p = 0.7). CT Compliance was 80% in AA and 53% in AB (p = 0.0002). Acute G3/G4 toxicity was 35.8% in AA and 27.6% in AB (p = 0.23). With a median follow-up of 48.5 months (IQR 33–72), the five-year DFS was 72.3% with AA and 68.3% with AB (p = 0.74), the five-year OS 83.8% for AA and 82.2% for AB (p = 0.53), and the five-year local recurrence was 6.3% for AA and 5.8% for AB (p = 0.71). Conclusion We confirmed improved compliance to neoadjuvant CT in this study. Although there is no statistical difference in ypT0N0 rate, local recurrence, and DFS between the two arms, a trend towards favourable oncological outcomes is observed.

Background. Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a progressive disorder where upper and lower extremities motor performances may bring participation restriction. Purpose. To document participation in adults with ARSAC and explore associations with motor performances. Method. Twenty-eight participants took part in the study. Participation was assessed using the LIFE-H. Motor performance was assessed using several outcomes including the SARA, LEMOCOT, Berg Balance Scale, 10-Meter Walk Test, and Finger-to-nose Test. Findings. Participation was significantly lower in the wheelchair user subgroup. Also, for 29 activities out of 77, at least 15% of participants reported severely disrupted participation. Participation was correlated with upper and lower limbs coordination, walking ability, balance, disease severity, and fine dexterity (Spearman r = .41–0.85, p

Glaciated margins on the Antarctic continental shelf comprise a mixture of substrate types, with areas of hard bedrock exposed by glacial erosion, glacial diamict deposits comprising mixed clasts, and dropstones deposited during ice sheet retreat and iceberg melt. Soft sediments accumulate in deeply eroded glacial troughs and depressions. Seabed substrates clearly delineate benthic habitats on the Sabrina Coast shelf, with significant increases in taxa diversity, abundance, and biological cover observed on hard substrates such as dropstones and areas of exposed bedrock, compared to soft substrates. Some taxa, including the hexactinellid sponge Anoxycalyx joubini, branching hydrocorals, several gorgonians, and colonial ascidians, were found only in areas of hard substrates. The largely random distribution of dropstones across glaciated shelves creates fine-scale habitat heterogeneity that is important not only for the distribution of the seafloor biota, but also for their dispersal.

Background Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) is a recessive neurological disorder with cerebellar, pyramidal and neuropathic features. Natural history data are urgently needed to increase trial readiness. This study aimed to describe the clinical phenotype including dexterity, coordination, strength, mobility, balance, disease severity, participation, and quality of life observed in adults with ARSACS homozygous for the c.8844delT mutation. Methods Cross-sectional study with comparisons between disease stages and with reference values. Outcome measures included Standardized Finger-to-Nose Test, Grip/pinch strength, LEMOCOT, Six-Minute Walk Test, 10-Meter Walk Test, Berg Balance Scale, Spastic Paraplegia Rating Scale, Scale for the Assessment and Rating of Ataxia, LIFE-H, and SF-12. Results Twenty-eight participants were recruited with a mean age of 38.1 years. The majority presented with lower limb coordination and fine dexterity scores below three standard deviations compare to reference values, scored under predicted values for mobility measures and were at increased risk of fall. Participants at an earlier disease stage performed better than the others, but individual variability was observed. Conclusions Results showed overall impaired motor performances and, even in a genetically homogeneous ARSACS population, an individual variability within disease stages. This study lays the foundation for a longitudinal study using quantified measurements.

ObjectiveTo document the decline of upper and lower limb functions, mobility, and independence in daily living activities in adults with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) over a 2-year period.MethodsAn exploratory longitudinal design was used. Nineteen participants were assessed on 2 occasions 2 years apart. Assessments included the Standardized Finger Nose Test, Nine-Hole Peg Test, Lower Extremity Motor Coordination Test, Berg Balance Scale, 10-m walk test (10mWT), 6-minute walk test (6MWT), Scale for the Assessment and Rating of Ataxia (SARA), and Barthel Index.ResultsA significant decline was observed between baseline and follow-up for lower limb coordination, balance, walking abilities (10mWT and 6MWT), and overall disease severity (SARA). All differences were beyond measurement error documented in ARSACS. Results showed no significant decline for upper limb coordination and fine dexterity performance.ConclusionAlthough ARSACS is a slow, progressive disease, results showed that mobility, balance, and lower limb performance significantly decreased over the 2-year period and that selected outcome measures were able to capture this decline beyond measurement errors.

Objective Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neuromuscular disease leading to several impairments, including decrease of lower limb coordination. The Lower Extremity Motor Coordination Test (LEMOCOT) is an outcome measure recently developed for stroke population. The aim of this study was to document: 1) intra- and interrater reliability; 2) the standard error of measurement and minimal detectable change; and 3) the construct validity of the measurements obtained with the LEMOCOT in the adult ARSACS population. Results The LEMOCOT has shown a good intra- and interrater reliability with an intraclass correlation coefficient ranging from 0.92 to 0.97 for both dominant and non-dominant side. The construct validity (hypothesis testing) is satisfying where LEMOCOT's score negatively correlated with participants' age ( r = − 0.74) and the score of the Scale for the Assessment and Rating of Ataxia ( r = − 0.86) and positively correlated with the balance and mobility tests ( r = 0.82 with the Berg Balance Scale, r = 0.61 with the Six-Minute Walk Test, r = 0.57 with the 10-Meter Walk Test). The LEMOCOT was also able to distinguish between patients according to disease stages. Conclusion The LEMOCOT is a valid and reliable tool to assess lower limb coordination in the ARSACS population for whom the lack of coordination is a common symptom.

During the Last Glacial Maximum, grounded ice from the expanded Antarctic Peninsula Ice Sheet extended across the continental shelf. Grounded and flowing ice created a distinctive array of glacial geomorphic features on the sea floor, which were then exposed as the ice sheet retreated. The recent disintegration of the northern parts of the Larsen Ice Shelf (Larsen A and B) have permitted acquisition of marine geophysical data in previously inaccessible and unmapped areas. We present a reconstruction of the evolving ice-flow path and ice sheet geometry of the eastern Antarctic Peninsula, with particular focus paid to newly surveyed areas that shed light on the dynamics of a marine-terminating glacial geomorphic environment, where ice shelves play a major role in grounding line stability. Shifting flow directions were mapped in several areas, including across the Seal Nunataks, which divide Larsen A and B, and offshore of Larsen C, indicating flow reorientation that reflects the changing ice sheet geometry as retreat neared the modern coastline. The measured flow indicators in this area reveal comparatively high elongation ratios (> 20), indicating rapid ice flow. Evidence of possible previous ice-shelf collapses are noted near the shelf break, further illustrating the critical, protective effect that ice shelves impart to marine-terminating glacial environments. Modern ice retreat is governed in part by reorganization of flow patterns accompanying grounding line movement; such reorganizations happened in the past and can aid understanding of modern processes.

Radiotherapy can affect the electronic components of a cardiac implantable electronic device (CIED) resulting in malfunction and/or damage. We sought to assess the incidence, predictors, and clinical impact of CIED dysfunction (CIED-D) after radiotherapy for cancer treatment. Clinical characteristics, cancer, different types of CIEDs, and radiation dose were evaluated. The investigation identified 230 patients, mean age 78 ± 8 years and 70% were men. A total of 199 patients had pacemakers (59% dual chamber), 21 (9%) cardioverter-defibrillators, and 10 (4%) resynchronizators or defibrillators. The left pectoral (n = 192, 83%) was the most common CIED location. Sixteen patients (7%) experienced 18 events of CIED-D after radiotherapy. Reset to backup pacing mode was the most common encountered dysfunction, and only 1 (6%) patient of those with CIED-D experienced symptoms of atrioventricular dyssynchrony. Those who had CIED-D tended to have a shorter device age at the time of radiotherapy compared to those who did not (2.5 ± 1.5 vs 3.8 ± 3.4 years, p = 0.09). The total dose prescribed to the tumor was significantly greater among those who had CIED-D (66 ± 30 vs 42 ± 23 Gy, p0.0001). Multivariate logistic regression analysis identified the total dose prescribed to the tumor as the only independent predictor for CIED-D (odds ratio 1.19 for each increase in 5 Gy, 95% confidence interval 1.08 to 1.31, p = 0.0005). In conclusion, in this large population of patients with CIEDs undergoing radiotherapy for cancer treatment, the occurrence of newly diagnosed CIED-D was 7%, and the reset to backup pacing mode was the most common encountered dysfunction. The total dose prescribed to the tumor was a predictor of CIED-D. Importantly, although the unpredictability of CIEDs under radiotherapy is still an issue, none of our patients experienced significant symptoms, life-threatening arrhythmias, or conduction disorders.

This study presents the first analysis of benthic megafauna and habitats from the Sabrina Coast shelf, encompassing a proposed Marine Protected Area. Sea bed imagery indicated an abundant benthic fauna compared to other parts of the Antarctic shelf, dominated by brittle stars, polychaete tubeworms, and a range of other sessile and mobile taxa. The distribution of taxa was related (ρ=0.592, PAnoxycalyx joubini and branching hydrocorals exhibited a more restricted distribution, probably related to water depth and limited dispersal capability, respectively. Dropstones were associated with significant increases in taxa diversity, abundance and biological cover, enhancing the overall diversity and biomass of this ecosystem.

The northern Antarctic Peninsula (NAP) forms a narrow stretch of land that extends to a relatively low latitude (63° S) and is subject to a humid, maritime-influenced climate, especially on its western side. During the Last Glacial Maximum (LGM), the NAP was covered by the northern part of the Antarctic Peninsula Ice Sheet (APIS) (Lavoie et al. 2015). The APIS fed ice streams flowing on both sides of the NAP, including the Gerlache–Boyd Ice Stream (GBIS) (Canals et al. 2000). Fast-flowing ice streams are the most dynamic components of ice sheets and largely determine ice-sheet mass loss and stability (Bentley 1987; Bamber et al. 2000). They transport large volumes of sediments both subglacially and englacially, and shape a variety of landforms both on land and the seafloor (e.g. Dowdeswell & Elverhoi 2002). During the LGM and throughout deglaciation, the role of ice streams was particularly significant. We describe the landforms associated with the GBIS based on a comprehensive compilation of multibeam bathymetry. The set of landforms and deposits left by the GBIS ranges in age from LGM to present, and illustrates both the products of ice-stream dynamics and how post-glacial processes can mask this glacial imprint. Our aim is to understand the dynamics of the GBIS and its temporal evolution since the LGM. In addition, the role of underlying geological control on the overall physiography of the GBIS is assessed. The study area extends 365 km from the southern end of Gerlache Strait (GS) to the South Shetland deep-sea trench and is fed by a glacierized catchment of about 23 000 km2 (Fig. 1a) (Canals et al. 2000). The height difference from the ice divide to the deep-sea trench is c. 6700 m. The GBIS system was the main drainage pathway of this catchment (O Cofaigh et …

Objective To document in adults affected by autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) the intra- and interrater reliability, standard error of measurement, agreement, minimal detectable change, and construct validity of the 9-Hole Peg Test (NHPT), the Standardized Finger-to-Nose Test (SFNT), and grip strength. Design Metrologic study. Setting Neuromuscular rehabilitation clinic. Participants Genetically confirmed adult patients with ARSACS (N=42; 21 women; mean age, 38.6y). Interventions Not applicable. Main outcome measures Intra- and interrater reliability was determined using the intraclass correlation coefficient (ICC). Construct validity was determined by assessing the capacity of the NHPT, the SFNT, and grip strength to distinguish between participants based on sex, mobility stages, and age groups, and on performance on the Archimedes spiral and fast alternating hand movements tests. Results All 3 tests have shown excellent reliability (ICC=.90-.98). However, the limit of agreement was influenced by the participant's performance on the NHPT, and the minimal detectable change was very different for both hands (right=9.7 vs left=28.0). Construct validity was confirmed for the SFNT and NHPT, but it was not demonstrated for grip strength. Conclusions Given the metrologic properties assessed in this study, the SFNT is an excellent measure to assess upper limb coordination, whereas the NHPT must be used with caution. The grip strength is reliable but does not seem to reflect disease severity.

Objective To assess the construct validity of the 10-Meter Walk Test (10mWT), Six-Minute Walk Test (6MWT), Berg Balance Scale (BERG), and Timed Up and Go (TUG) in adults with Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS), in addition to the interrater reliability of the 10mWT and 6MWT. Methods Reliability was determined using the intraclass correlation coefficient (ICC). Validity was determined first by correlating the 10mWT, 6MWT, BERG, and TUG with participant's age, lower limb coordination, and disease severity, and then by assessing their capacity to distinguish between participants based on sex and disease stages. Results Interrater reliability of the 10mWT at both comfortable and maximum speed as well as the 6MWT is excellent (ICC = 0.97–0.99). Construct validity of the four tests was confirmed, as showed by the high correlations with age, lower limb coordination, and overall disease severity (ρ = 0.64–0.97). Conclusions The four tests assessed for their metrological properties in this study showed to be valid instruments to use in the ARSACS population. The 10mWT and 6MWT are also highly reliable. BERG and TUG reliability will need to be assess in a future study.

Three marine sediment cores were collected along the length of the fjord axis of Barilari Bay, Graham Land, west Antarctic Peninsula (65°55′S, 64°43′W). Multi-proxy analytical results constrained by high-resolution geochronological methods ( 210 Pb, radiocarbon, 137 Cs) in concert with historical observations capture a record of Holocene paleoenvironmental variability. Our results suggest early and middle Holocene (>7022–2815 cal. [calibrated] yr B.P.) retreated glacial positions and seasonally open marine conditions with increased primary productivity. Climatic cooling increased sea ice coverage and decreased primary productivity during the Neoglacial (2815 to cal. 730 cal. yr B.P.). This climatic cooling culminated with glacial advance to maximum Holocene positions and expansion of a fjord-wide ice shelf during the Little Ice Age (LIA) (ca. 730–82 cal. yr B.P.). Seasonally open marine conditions were achieved and remnant ice shelves decayed within the context of recent rapid regional warming (82 cal. yr B.P. to present). Our findings agree with previously observed late Holocene cooling and glacial advance across the Antarctic Peninsula, suggesting that the LIA was a regionally significant event with few disparities in timing and magnitude. Comparison of the LIA Antarctic Peninsula record to the rest of the Southern Hemisphere demonstrates close synchronicity in the southeast Pacific and southern most Atlantic region but less coherence for the southwest Pacific and Indian Oceans. Comparisons with the Northern Hemisphere demonstrate that the LIA Antarctic Peninsula record was contemporaneous with pre-LIA cooling and sea ice expansion in the North Atlantic–Arctic, suggesting a global reach for these events.

Importance Chemoradiotherapy (CRT), followed by surgery, is the recommended approach for stage II and III rectal cancer. While CRT decreases the risk of local recurrence, it does not improve survival and leads to poorer functional outcomes than surgery alone. Therefore, new approaches to better select patients for CRT are important. Objective To conduct a phase 2 study to evaluate the safety and feasibility of using magnetic resonance imaging (MRI) criteria to select patients with “good prognosis” rectal tumors for primary surgery. Design, Setting, and Participants Prospective nonrandomized phase 2 study at 12 high-volume colorectal surgery centers across Canada. From September 30, 2014, to October 21, 2016, a total of 82 patients were recruited for the study. Participants were patients newly diagnosed as having rectal cancer with MRI-predicted good prognosis rectal cancer. The MRI criteria for good prognosis tumors included distance to the mesorectal fascia greater than 1 mm; definite T2, T2/early T3, or definite T3 with less than 5 mm of extramural depth of invasion; and absent or equivocal extramural venous invasion. Interventions Patients with rectal cancer with MRI-predicted good prognosis tumors underwent primary surgery. Main Outcomes and Measures The primary outcome was the proportion of patients with a positive circumferential resection margin (CRM) rate. Assuming a 10% baseline probability of a positive CRM, a sample size of 75 was estimated to yield a 95% CI of ±6.7%. Results Eighty-two patients (74% male) participated in the study. The median age at the time of surgery was 66 years (range, 37-89 years). Based on MRI, most tumors were midrectal (65% [n = 53]), T2/early T3 (60% [n = 49]), with no suspicious lymph nodes (63% [n = 52]). On final pathology, 91% (n = 75) of tumors were T2 or greater, 29% (n = 24) were node positive, and 59% (n = 48) were stage II or III. The positive CRM rate was 4 of 82 (4.9%; 95% CI, 0.2%-9.6%). Conclusions and Relevance The use of MRI criteria to select patients with good prognosis rectal cancer for primary surgery results in a low rate of positive CRM and suggests that CRT may not be necessary for all patients with stage II and III rectal cancer. Trial Registration ISRCTN.com identifier:ISRCTN05107772