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Gastrointestinal carcinomas are genomically complex cancers that are lethal in the metastatic setting. Whole-genome and transcriptome sequencing allow for the simultaneous characterization of multiple oncogenic pathways. We report 3 cases of metastatic gastrointestinal carcinoma in patients enrolled in the Personalized Onco-Genomics program at the BC Cancer Agency. Real-time genomic profiling was combined with clinical expertise to diagnose a carcinoma of unknown primary, to explore treatment response to bevacizumab in a colorectal cancer, and to characterize an appendiceal adenocarcinoma. In the first case, genomic profiling revealed an IDH1 somatic mutation, supporting the diagnosis of cholangiocarcinoma in a malignancy of unknown origin, and further guided therapy by identifying epidermal growth factor receptor amplification. In the second case, a BRAF V600E mutation and wild-type KRAS profile justified the use of targeted therapies to treat a colonic adenocarcinoma. The third case was an appendiceal adenocarcinoma defined by a p53 inactivation, Ras/raf/mek, Akt/mtor, Wnt, and notch pathway activation, and overexpression of ret, erbb2 (her2), erbb3, met, and cell cycle regulators. We show that whole-genome and transcriptome sequencing can be achieved within clinically effective timelines, yielding clinically useful and actionable information.

© 2014 American Chemical Society. This work presents a systematic investigation of the molecular level composition and the extent of aqueous photochemical processing in different types of secondary organic aerosol (SOA) from biogenic and anthropogenic precursors including α-pinene, β-pinene, β-myrcene, d-limonene, α-humulene, 1,3,5-trimethylbenzene, and guaiacol, oxidized by ozone (to simulate a remote atmosphere) or by OH in the presence of NOx (to simulate an urban atmosphere). Chamber- and flow-tube-generated SOA samples were collected, extracted in a methanol/water solution, and photolyzed for 1 h under identical irradiation conditions. In these experiments, the irradiation was equivalent to about 3-8 h of exposure to the sun in its zenith. The molecular level composition of the dissolved SOA was probed before and after photolysis with direct-infusion electrospray ionization high-resolution mass spectrometry (ESI-HR-MS). The mass spectra of unphotolyzed SOA generated by ozone oxidation of monoterpenes showed qualitatively similar features and contained largely overlapping subsets of identified compounds. The mass spectra of OH/NOx-generated SOA had more unique visual appearance and indicated a lower extent of product overlap. Furthermore, the fraction of nitrogen-containing species (organonitrates and nitroaromatics) was highly sensitive to the SOA precursor. These observations suggest that attribution of high-resolution mass spectra in field SOA samples to specific SOA precursors should be more straightforward under OH/NOx oxidation conditions compared to the ozone-driven oxidation. Comparison of the SOA constituents before and after photolysis showed the tendency to reduce the average number of atoms in the SOA compounds without a significant effect on the overall O/C and H/C ratios. SOA prepared by OH/NOx photooxidation of 1,3,5-trimethylbenzene and guaiacol were more resilient to photolysis despite being the most light-absorbing. The composition of SOA prepared by ozonolysis of monoterpenes changed more significantly as a result of the photolysis. The results indicate that aqueous photolysis of dissolved SOA compounds in cloud/fog water can occur in various types of SOA, and on atmospherically relevant time scales. However, the extent of the photolysis-driven change in molecular composition depends on the specific type of SOA.

Atmospheric absorption by brown carbon aerosol may play an important role in global radiative forcing. Brown carbon arises from both primary and secondary sources, but the mechanisms and reactions of the latter are highly uncertain. One proposed mechanism is the reaction of ammonia or amino acids with carbonyl products in secondary organic aerosol (SOA). We generated SOA in situ by reacting biogenic alkenes (α-pinene, limonene, and α-humulene) with excess ozone, humidifying the resulting aerosol, and reacting the humidified aerosol with gaseous ammonia. We determined the complex refractive indices (RI) in the 360-420 nm range for these aerosols using broadband cavity enhanced spectroscopy (BBCES). The average real part (n) of the measured spectral range of the NH3-aged α-pinene SOA increased from n = 1.50 (±0.01) for the unreacted SOA to n = 1.57 (±0.01) after 1.5 h of exposure to 1.9 ppm NH3, whereas the imaginary component (k) remained below. For the limonene and α-humulene SOA the real part did not change significantly, and we observed a small change in the imaginary component of the RI. The imaginary component increased from k = 0.000 to an average k = 0.029 (±0.021) for α-humulene SOA, and from to an average k = 0.032 (±0.019) for limonene SOA after 1.5 h of exposure to 1.3 and 1.9 ppm of NH3, respectively. Collected filter samples of the aged and unreacted α-pinene SOA and limonene SOA were analyzed off-line by nanospray desorption electrospray ionization high resolution mass spectrometry (nano-DESI/HR-MS), and in situ using a Time-of-Flight Aerosol Mass Spectrometer (ToF-AMS), confirming that the SOA reacted and that various nitrogen-containing reaction products formed. If we assume that NH3aging reactions scale linearly with time and concentration, which will not necessarily be the case in the atmosphere, then a 1.5 h reaction with 1 ppm NH3in the laboratory is equivalent to 24 h reaction with 63 ppbv NH3, indicating that the observed aerosol absorption will be limited to atmospheric regions with high NH3concentrations. This journal is © the Partner Organisations 2014.

Carpal tunnel syndrome is prevalent among individuals who are wheelchair dependent. Maximal electrophysiologic median nerve dysfunction has been isolated to the proximal part of the carpal tunnel--the site of hand-wheel interface during wheeling. The objective of this study was to determine if measurable median nerve dysfunction (conduction slowing or block) results from a single session of vigorous wheeling and, if so, if protection for the hand with a glove (padded over the region of the carpal tunnel) could minimize the dysfunction. Thirty-five subjects (16 wheelchair dependent; 19 able-bodied) propelled a roller-mounted wheelchair at maximal rate of 2,000 hand strikes. A protective glove was worn on 1 hand only. Immediately before and after the wheeling, hand surface temperatures and bilateral median motor and sensory conductions were performed, and across-carpal tunnel conduction velocity and conduction block were calculated. Another group of 11 able-bodied subjects underwent similar electrodiagnostic testing before and after one half hour of vigorous stationary cycling (no hand trauma). Results were analyzed using a three-way analysis of covariance for repeated measures and demonstrated that (1) significant increases (5.2% to 8.5%) in across carpal tunnel conduction block occurred as a result of wheelchair propulsion but not cycling; (2) the wheeling-induced conduction block was not altered by using a protective glove. This study has demonstrated a model for measuring acute median nerve dysfunction resultant from wheeling but raises doubts regarding the protective effect of glove use on median nerve function.