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On the 'easy' climbs up Mexico's volcanoes, ignorance and arrogance can be deadly. A classic story from the Backpacker archives. This classic story originally ran in the February 1996 issue [...]

Editor's Note: With a September heat wave subjecting the western U.S. to record temperatures, we're making this subscriber-only story from our print archive available to everyone. Support more great skills [...]

Mountain gorillas, today one of the most beloved wild animals on the planet. were little known four decades ago when the American primatologist Dian Fosscy, commenting on a spate of [...]

THE SUN IS STILL HIGH IN THE ALASKAN SUMMER SKY WHEN THE CALL COMES IN AT 9:47 P.M. SIRENS WAIL, AND EIGHT SMOKEJUMPERS race to the suit-up racks. Already in [...]

WITH A TREKKING POLE IN ONE HAND and an ice ax in the other, I am naked except for the rigid mountaineering boots on my feet. With all my clothes [...]

I typically get a bit excited about movie sequels despite their historically bad reputations. I have enjoyed a few: The Empire Strikes Back, Aliens, Star Trek II--Wrath of Khan, Godfather [...]

12 p.m. Brandberg mountain is burning. A remorseless globe of sun is scalding the sky. Rocks scattered on the mountain are too hot to touch. Shade is the only shield [...]

'BE CAREFUL FOR THIS ONE,' says Jonathan Domondon as he delicately steps over a thorny branch fallen across the trail. 'We call it lupa. If it touches your skin, it [...]

The wind slams into me, and I desperately grip my ice axes to keep from being ripped off the mountain face. I push my head against the snow, calm myself, [...]

Identifying tumor DNA mismatch repair deficiency (dMMR) is important for precision medicine. Tumor features, individually and in combination, derived from whole-exome sequenced (WES) colorectal cancers (CRCs) and panel-sequenced CRCs, endometrial cancers (ECs), and sebaceous skin tumors (SSTs) were assessed for their accuracy in detecting dMMR. CRCs (n= 300) with WES, where mismatch repair status was determined by immunohistochemistry, were assessed for microsatellite instability (MSMuTect, MANTIS, MSIseq, and MSISensor), Catalogue of Somatic Mutations in Cancer tumor mutational signatures, and somatic mutation counts. A 10-fold cross-validation approach (100 repeats) evaluated the dMMR prediction accuracy for i) individual features, ii) Lasso statistical model, and iii) an additive feature combination approach. Panel-sequenced tumors (29 CRCs, 22 ECs, and 20 SSTs) were assessed for the top performing dMMR predicting features/models using these three approaches. For WES CRCs, 10 features provided >80% dMMR prediction accuracy, with MSMuTect, MSIseq, and MANTIS achieving ≥99% accuracy. The Lasso model achieved 98.3% accuracy. The additive feature approach, with three or more of six of MSMuTect, MANTIS, MSIseq, MSISensor, insertion-deletion count, or tumor mutational signature small insertion/deletion 2 + small insertion/deletion 7 achieved 99.7% accuracy. For the panel-sequenced tumors, the additive feature combination approach of three or more of six achieved accuracies of 100%, 95.5%, and 100% for CRCs, ECs, and SSTs, respectively. The microsatellite instability calling tools performed well in WES CRCs; however, an approach combining tumor features may improve dMMR prediction in both WES and panel-sequenced data across tissue types.

Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.

Surface cracks are a common sight on public infrastructure nowadays. Recent work has been addressing this problem by supporting structural maintenance measures using machine learning methods. Those methods are used to segment surface cracks from their background, making them easier to localize. However, a common issue is that to create a well-functioning algorithm, the training data needs to have detailed annotations of pixels that belong to cracks. Our work proposes a weakly supervised approach that leverages a CNN classifier in a novel way to create surface crack pseudo labels. First, we use the classifier to create a rough crack localization map by using its class activation maps and a patch based classification approach and fuse this with a thresholding based approach to segment the mostly darker crack pixels. The classifier assists in suppressing noise from the background regions, which commonly are incorrectly highlighted as cracks by standard thresholding methods. Then, the pseudo labels can be used in an end-to-end approach when training a standard CNN for surface crack segmentation. Our method is shown to yield sufficiently accurate pseudo labels. Those labels, incorporated into segmentation CNN training using multiple recent crack segmentation architectures, achieve comparable performance to fully supervised methods on four popular crack segmentation datasets.

Large heads bowed, snow coating their thick hides, plumes of steam swirling from their frosted nostrils, they're primordial beasts genetically inured to intense cold. A wooden sleigh called a chana [...]

The only way to truly appreciate America's vast, diverse wilderness? Hike it all. They say you only get one chance to make a first impression. Fortunately, Steve Brumbach had two [...]

Thank you to everyone at Stereophile for taking the time to complete such an authentic review of our flagship K50 music server. Jason has described the essence of the music-making [...]

Joe Kelsey was moving gracefully on granite. Long and lean, with meaty hands, he studied the rock before him and eyed the vertical face before deftly stepping up. Every move [...]

Models used to predict the probability of an individual having a pathogenic homozygous or heterozygous variant in a mismatch repair gene, such as MMRpro, are widely used. Recently, MMRpro was updated with new colorectal cancer penetrance estimates. The purpose of this study was to evaluate the predictive performance of MMRpro and other models for individuals with a family history of colorectal cancer.

The hunting party slowly glides into the Altay Mountains in search of elk. It is dead calm, minus 38°F. Just as their ancestors have for millennia, the five men traverse [...]

YOU DON'T HAVE TO TRAVEL FAR TO DISCOVER THE WORLD'S MOST ANCIENT SACRED PLACES. JUST OPEN YOUR EYES. Taj Mahal. Parthenon. Colosseum. Eiffel Tower. Angkor Wat. Great Wall. I attended [...]

An hour above high camp on the Southeast Ridge of Everest, Panuru Sherpa and I passed the first body. The dead climber was on his side, as if napping in [...]

To the north, glacier-crusted, 24,790foot Minya Konka cut into the horizon like a diamond. To the west, the endless mountains of the peak-spiked, 12,000-foot Tibetan plateau broke the skyline. To [...]

Neither of us slept that night. Twice, avalanches nearly killed us. We just lay in our tent, listening as intently as soldiers, straining to interpret the portent of each explosion. [...]

IT'S TWO IN THE MORNING AND A KOALA IS CAUGHT IN BARBED WIRE ON A FENCH, LIKE A PRISONER TRYING TO ESCAPE. A phone rings in the home of Megan [...]

She is lying in a cave, dying. Legs and arms but knobby sticks, Lidia Maiyu is curled up close to the campfire. Her eyes are wide in apprehension of death. [...]

The lions appear one by one, like ghosts. They are the exact color of the tall, dry grass, a raw sienna. Before we know it, 14 muscled, yellow-eyed great cats [...]

DELICATELY BRUSHING AWAY THE SOIL with his fingers, Aki Ra uncovers a dark green land mine buried two inches beneath the overgrown dirt road. The size of a large soup [...]

The Swiss have mountains, so they climb. Canadians have lakes, so they canoe. The Australians have canyons, so they go canyoneering, a hybrid form of madness halfway between mountaineering and [...]

I had a large bulge the size of a peach protruding from my groin. I knew where the hernia came from: carrying too many heavy packs. It first popped out [...]

On a bright Saturday morning in September a young man is clinging to the face of Half Dome, a sheer 2,130-foot wall of granite in the heart of Yosemite Valley. [...]

'Past the hand of dog, watch out for dinosaurs,' says a voice in the dark. I recognize Jonathan Sims's clipped, British military accent but have no idea what he's talking [...]

[ILLUSTRATION OMITTED] Maligiaq Padilla, perhaps the greatest sea kayaker in the world, is being dragged sideways through the icebergs by a surrogate walrus. A harpoon line is wrapped beneath his [...]

At first glance Greenland is an expanse of blinding white. But as my chopper swings low over the island, color catches my eye. For miles on end, bands of blue [...]

[ILLUSTRATION OMITTED] [ILLUSTRATION OMITTED] Deep in the mountains of western Sichuan I'm hacking through a bamboo jungle, trying to find a legendary trail. Just 60 years ago, when much of [...]

Background Being overweight or obese is an established risk factor for colorectal cancer, more so for men than for women. Approximately 10%-20% of colorectal tumors display microsatellite instability (MSI), defined as the expansion or contraction of small repeated sequences in the DNA of tumor tissue relative to nearby normal tissue. We evaluated associations between overweight or obesity and colorectal cancer risk, overall and by tumor MSI status. Methods The study included 1794 case subjects with incident colorectal cancer who were identified through population-based cancer registries and 2684 of their unaffected sex-matched siblings as control subjects. Recent body mass index (BMI), BMI at age 20 years, and adult weight change were derived from self-reports of height and weight. Tumor MSI status, assessed at as many as 10 markers, was obtained for 69.7% of the case subjects and classified as microsatellite (MS)-stable (0% of markers unstable; n = 913), MSI-low (>0% but Results Recent BMI, modeled in 5 kg/[m.sup.2] increments, was positively associated with risk of colorectal cancer for men and women combined (OR = 1.24; 95% CI = 1.15 to 1.34), for women only (OR = 1.20; 95% CI = 1.10 to 1.32), and for men only (OR = 1.30; 95% CI = 1.15 to 1.47). There was no interaction with sex (P= .22). Recent BMI, per 5 kg/[m.sup.2], was positively associated with the risk of MS-stable (OR = 1.38; 95% CI = 1.24 to 1.54) and MSI-low (OR = 1.33; 95% CI = 1.04 to 1.72) colorectal tumors, but not with the risk of MSI-high tumors (OR = 1.05; 95% CI = 0.84 to 1.31). Conclusion The increased risk of colorectal cancer associated with a high BMI might be largely restricted to tumors that display the more common MS-stable phenotype, suggesting further that colorectal cancer etiology differs by tumor MSI status. DOI: 10.1093/jnci/djq011