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1. WINDOWS 12 WHAT WE WANT: WITH THE NEXT VERSION OF WINDOWS LIKELY TO LAND BEFORE THE END OF THE YEAR, OUR CONTRIBUTORS REVEAL WHAT NEW FEATURES THEY WANT--AND WHAT OLD FEATURES THEY'D LIKE TO SEE THE BACK OF

Author

Cassidy, Steve, Collins, Barry, Danton, Tim, Graham-Smith, Darien, Grant, Lee, Honeyball, Jon, Rawlinson, Nik, and Winder, Davey

Subjects
Operating systems, 64-bit operating system, 32-bit operating system, Operating system, Science and technology
Abstract

We live in hope. Hope that Microsoft commits to a full new operating system this autumn rather than yet another feature update, as some predict. But most of all we [...]

Published
2024

2. Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Author

Pål Møller, Toni Seppälä, James G. Dowty, Saskia Haupt, Mev Dominguez-Valentin, Lone Sunde, Inge Bernstein, Christoph Engel, Stefan Aretz, Maartje Nielsen, Gabriel Capella, Dafydd Gareth Evans, John Burn, Elke Holinski-Feder, Lucio Bertario, Bernardo Bonanni, Annika Lindblom, Zohar Levi, Finlay Macrae, Ingrid Winship, John-Paul Plazzer, Rolf Sijmons, Luigi Laghi, Adriana Della Valle, Karl Heinimann, Elizabeth Half, Francisco Lopez-Koestner, Karin Alvarez-Valenzuela, Rodney J. Scott, Lior Katz, Ido Laish, Elez Vainer, Carlos Alberto Vaccaro, Dirce Maria Carraro, Nathan Gluck, Naim Abu-Freha, Aine Stakelum, Rory Kennelly, Des Winter, Benedito Mauro Rossi, Marc Greenblatt, Mabel Bohorquez, Harsh Sheth, Maria Grazia Tibiletti, Leonardo S. Lino-Silva, Karoline Horisberger, Carmen Portenkirchner, Ivana Nascimento, Norma Teresa Rossi, Leandro Apolinário da Silva, Huw Thomas, Attila Zaránd, Jukka-Pekka Mecklin, Kirsi Pylvänäinen, Laura Renkonen-Sinisalo, Anna Lepisto, Päivi Peltomäki, Christina Therkildsen, Lars Joachim Lindberg, Ole Thorlacius-Ussing, Magnus von Knebel Doeberitz, Markus Loeffler, Nils Rahner, Verena Steinke-Lange, Wolff Schmiegel, Deepak Vangala, Claudia Perne, Robert Hüneburg, Aída Falcón de Vargas, Andrew Latchford, Anne-Marie Gerdes, Ann-Sofie Backman, Carmen Guillén-Ponce, Carrie Snyder, Charlotte K. Lautrup, David Amor, Edenir Palmero, Elena Stoffel, Floor Duijkers, Michael J. Hall, Heather Hampel, Heinric Williams, Henrik Okkels, Jan Lubiński, Jeanette Reece, Joanne Ngeow, Jose G. Guillem, Julie Arnold, Karin Wadt, Kevin Monahan, Leigha Senter, Lene J. Rasmussen, Liselotte P. van Hest, Luigi Ricciardiello, Maija R. J. Kohonen-Corish, Marjolijn J. L. Ligtenberg, Melissa Southey, Melyssa Aronson, Mohd N. Zahary, N. Jewel Samadder, Nicola Poplawski, Nicoline Hoogerbrugge, Patrick J. Morrison, Paul James, Grant Lee, Rakefet Chen-Shtoyerman, Ravindran Ankathil, Rish Pai, Robyn Ward, Susan Parry, Tadeusz Dębniak, Thomas John, Thomas van Overeem Hansen, Trinidad Caldés, Tatsuro Yamaguchi, Verónica Barca-Tierno, Pilar Garre, Giulia Martina Cavestro, Jürgen Weitz, Silke Redler, Reinhard Büttner, Vincent Heuveline, John L. Hopper, Aung Ko Win, Noralane Lindor, Steven Gallinger, Loïc Le Marchand, Polly A. Newcomb, Jane Figueiredo, Daniel D. Buchanan, Stephen N. Thibodeau, Sanne W. ten Broeke, Eivind Hovig, Sigve Nakken, Marta Pineda, Nuria Dueñas, Joan Brunet, Kate Green, Fiona Lalloo, Katie Newton, Emma J. Crosbie, Miriam Mints, Douglas Tjandra, Florencia Neffa, Patricia Esperon, Revital Kariv, Guy Rosner, Walter Hernán Pavicic, Pablo Kalfayan, Giovana Tardin Torrezan, Thiago Bassaneze, Claudia Martin, Gabriela Moslein, Aysel Ahadova, Matthias Kloor, Julian R. Sampson, Mark A. Jenkins, and The European Hereditary Tumour Group (EHTG) and the International Mismatch Repair Consortium (IMRC)

Subjects
Lynch Syndrome, Epidemiology, Prevention, Penetrance, Colorectal cancer, Segregation analysis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Genetics, QH426-470
Abstract

Abstract Objective To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. Results In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. Conclusions Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so.

Published
2022
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3. Reducing the risk of Plasmodium vivax after falciparum infections in co-endemic areas—a randomized controlled trial (PRIMA)

Author

Kamala Thriemer, Tamiru Shibru Degaga, Michael Christian, Mohammad Shafiul Alam, Benedikt Ley, Mohammad Sharif Hossain, Mohammad Golam Kibria, Tedla Teferi Tego, Dagimawie Tadesse Abate, Sophie Weston, Amalia Karahalios, Megha Rajasekhar, Julie A. Simpson, Angela Rumaseb, Hellen Mnjala, Grant Lee, Rodas Temesgen Anose, Fitsum Getahun Kidane, Adugna Woyessa, Kevin Baird, Inge Sutanto, Asrat Hailu, and Ric N. Price

Subjects
Vivax malaria, Falciparum malaria, Radical cure, Universal radical cure, Vivax elimination, Co-endemic, Medicine (General), R5-920
Abstract

Abstract Background Plasmodium vivax forms dormant liver stages that can reactivate weeks or months following an acute infection. Recurrent infections are often associated with a febrile illness and can cause a cumulative risk of severe anaemia, direct and indirect mortality, and onward transmission of the parasite. There is an increased risk of P. vivax parasitaemia following falciparum malaria suggesting a rationale for universal use of radically curative treatment in patients with P. falciparum malaria even in the absence of detectable P. vivax parasitaemia in areas that are co-endemic for both species. Methods This is a multicentre, health care facility-based, randomized, controlled, open-label trial in Bangladesh, Indonesia and Ethiopia. Patients with uncomplicated falciparum malaria, G6PD activity of ≥70% of the adjusted male median (AMM) and haemoglobin levels ≥8g/dl are recruited into the study and randomized to either receive standard schizonticidal treatment plus 7-day high dose primaquine (total dose 7mg/kg) or standard care in a 1:1 ratio. Patients are followed up weekly until day 63. The primary endpoint is the incidence risk of any P. vivax parasitemia on day 63. Secondary endpoints include incidence risk on day 63 of symptomatic P. vivax malaria and the risk of any P. falciparum parasitaemia. Secondary safety outcomes include the proportion of adverse events and serious adverse events, the incidence risk of severe anaemia (Hb

Published
2022
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4. “The more I have to do with UK telcos, the more broken their systems seem to be”.

Author

HONEYBALL, JON, Grant, Lee, Whitcroft, Olivia, Winder, Davey, and Cassidy, Steve

Subjects
APPLE Watch, TELECOMMUNICATION, RITUAL, PROFESSIONAL employees
Abstract

The article discusses the author's experience with upgrading to the iPhone 16 Pro Max and Apple Watch 2 Ultra, highlighting technical improvements and personal reasons for the upgrades. The author also explores challenges faced with migrating an eSIM from one Apple Watch to another, specifically with UK telcos, and expresses disappointment with wireless charging capabilities. Additionally, the article touches on the author's use of the Apple Vision Pro for entertainment and security camera options for home or office use. [Extracted from the article]

Published
2024

5. CYBERSPACE ODDITY The story of BowieNet.

Author

Grant, Lee

Subjects
INDUSTRIAL management, BUSINESS partnerships, INFORMATION superhighway, INTERNET access, FAN clubs, AVATARS (Virtual reality), ONLINE chat, DAUGHTERS
Abstract

The article discusses BowieNet, an online platform created by musician David Bowie in the late 1990s. BowieNet was an innovative internet service provider that allowed fans to connect with each other and with Bowie himself through features like chat rooms and message boards. It offered exclusive content and priority access to concert tickets. BowieNet was ahead of its time, introducing concepts like 3D avatars and virtual environments. Although the platform eventually dissolved, it remains a notable example of online innovation and created a strong sense of community among fans. [Extracted from the article]

Published
2024

6. WINDOWS 12 WHAT WE WANT.

Author

CASSIDY, STEVE, COLLINS, BARRY, DANTON, TIM, GRAHAM-SMITH, DARIEN, GRANT, LEE, HONEYBALL, JON, RAWLINSON, NIK, and WINDER, DAVEY

Subjects
ARTIFICIAL intelligence, MICROSOFT operating systems, COMPUTERS, THIRD-party software, MICROSOFT software, RANSOMWARE, MICROSOFT Azure (Computing platform)
Abstract

This article presents a compilation of desired features and improvements for the next version of Windows, referred to as Windows 12. The authors consulted experts and users to create a wishlist that includes better touch interface support, improved AI integration, a more cohesive user experience across devices, and enhanced performance. They also express a desire for a split-personality option for work and personal use, improved webcam software, and a commitment to ARM architecture. The authors hope that Microsoft will address these frustrations and deliver an operating system that meets their expectations. Additionally, the article discusses various features and improvements that would like to see in Windows 12, such as an open approach to storage, the ability to exclude certain updates and prevent driver updates, improved backup and system transfers, class-leading remote access and setup, more timely security updates, built-in protection against ransomware attacks, and changes to the user interface. The article also mentions the desire for a better touch interface, voice-typing capabilities without relying on the cloud, improved support for working from home, and better compatibility with ARM processors. Overall, the article provides a range of perspectives and suggestions for enhancing the Windows operating system. [Extracted from the article]

Published
2024

7. "Someone at Microsoft is making decisions that are turning my customers pretzel-shaped".

Author

GRANT, LEE

Subjects
DECISION making, CONSUMERS, VOLUNTEERS, VOLUNTEER service
Abstract

The article from PC Pro discusses the challenges faced by users due to Microsoft's implementation of OneDrive, leading to confusion and data loss for individuals like Carla. The author highlights the complexities of Microsoft's storage balancing system and the interconnection between OneDrive and Hotmail, causing issues for users. Additionally, the article includes anecdotes of repair experiences with laptops and monitors, emphasizing the importance of schematics in the repair process. The author encourages readers to engage in repair activities and support the PC Pro community for technical advice and solutions. [Extracted from the article]

Published
2025

8. "At our end of the retail tech world, most customers don't yet give a hoot about Copilot".

Author

GRANT, LEE

Subjects
CONSUMERS, CINNAMON, TOES, ROASTING (Cooking), SUMMER
Abstract

The article from PC Pro discusses the potential arrival of Windows 12 and the challenges faced by customers and retailers regarding Windows upgrades. It also delves into the introduction of Copilot and AI technology in the retail tech world, highlighting the struggles faced by Microsoft in promoting Copilot to consumers. Additionally, the article touches on the environmental impact of AI technology and Microsoft's efforts to push Copilot despite concerns about sustainability. The text also includes a section on LG laptops and the difficulties faced by repairers in sourcing spare parts. [Extracted from the article]

Published
2025

9. Renal cancer

Author

von Stempel, Conrad, primary, Grant, Lee Alexander, additional, Walkden, Miles, additional, and Ramachandran, Navin, additional

Published
2020
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11. “I make no apologies for my pedantry; Microsoft should know the names of its own products”.

Author

GRANT, LEE

Subjects
ARTIFICIAL intelligence, APOLOGIZING, VAMPIRES, POSTAL service, INSPIRATION
Abstract

The article from PC Pro discusses various real-world computing issues, including the confusion caused by Microsoft's name changes for Outlook and the challenges faced with laptop screens, particularly foldable ones. It highlights supply problems with laptop screens and the difficulties in finding compatible parts. The article also touches on keyboard replacement issues and a humorous anecdote about a cache-hogging TomTom software. The author also issues a correction regarding a Microsoft account command. [Extracted from the article]

Published
2024

12. Prospective validation of the NCI Breast Cancer Risk Assessment Tool (Gail Model) on 40,000 Australian women

Author

Carolyn Nickson, Pietro Procopio, Louiza S. Velentzis, Sarah Carr, Lisa Devereux, Gregory Bruce Mann, Paul James, Grant Lee, Cameron Wellard, and Ian Campbell

Subjects
Breast cancer screening, Validation, Gail model, Breast Cancer Risk Assessment Tool, Machine learning, Invasive breast cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background There is a growing interest in delivering more personalised, risk-based breast cancer screening protocols. This requires population-level validation of practical models that can stratify women into breast cancer risk groups. Few studies have evaluated the Gail model (NCI Breast Cancer Risk Assessment Tool) in a population screening setting; we validated this tool in a large, screened population. Methods We used data from 40,158 women aged 50–69 years (via the lifepool cohort) participating in Australia’s BreastScreen programme. We investigated the association between Gail scores and future invasive breast cancer, comparing observed and expected outcomes by Gail score ranked groups. We also used machine learning to rank Gail model input variables by importance and then assessed the incremental benefit in risk prediction obtained by adding variables in order of diminishing importance. Results Over a median of 4.3 years, the Gail model predicted 612 invasive breast cancers compared with 564 observed cancers (expected/observed (E/O) = 1.09, 95% confidence interval (CI) 1.00–1.18). There was good agreement across decile groups of Gail scores (χ2 = 7.1, p = 0.6) although there was some overestimation of cancer risk in the top decile of our study group (E/O = 1.65, 95% CI 1.33–2.07). Women in the highest quintile (Q5) of Gail scores had a 2.28-fold increased risk of breast cancer (95% CI 1.73–3.02, p

Published
2018
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13. “I think of myself as the Artful Bodger, a grubby-faced urchin that picks the pockets of OEMs”.

Author

GRANT, LEE

Subjects
RIGHT to repair movement, SPARE parts, PRICES, STORAGE batteries
Abstract

The article from PC Pro discusses the challenges faced by a PC repair shop in the repair-based retail industry, focusing on issues related to Right to Repair legislation, availability of spare parts, and firmware blocks preventing repairs. The author shares personal experiences with faulty components, third-party suppliers, and the impact of consumer laws on business-to-business transactions. The article emphasizes the need for practical and enforceable legislation to support a profitable repair economy and highlights the complexities of repair-retail in the real world. [Extracted from the article]

Published
2025

14. “The machine on my desk was a zombie PC. It was alive, but its brains had been sucked out”.

Author

GRANT, LEE

Subjects
DESKS, MACHINERY
Abstract

The article discusses the implementation of the EcoDesign for Sustainable Products Regulation (ESPR) in the European Union, which aims to promote durability, repairability, and circularity in electronic products. The author shares a personal experience of repairing a malfunctioning computer and highlights the importance of accessible repair options. The article also criticizes Virgin Media's implementation of multi-factor authentication (MFA) for its email service, which caused confusion and inconvenience for customers. Additionally, the author praises the modularity and repairability of the Fairphone, emphasizing the need for similar design practices in the industry. Overall, the article explores the potential impact of ESPR on reducing electronic waste and improving repairability. [Extracted from the article]

Published
2024

15. “The chances of goosing a PC while performing a simple upgrade should be almost zero. Almost”.

Author

GRANT, LEE

Subjects
GEESE, MACHINERY
Abstract

This article from PC Pro discusses various experiences and challenges faced by the author while performing PC upgrades and repairs. The author recounts their installation of the Kraken Elite RGB cooler and a 4TB M.2 SSD into a custom-built desktop. They also highlight the importance of checking motherboard specifications and limitations when upgrading or installing components. The article further touches on the impact of Windows 10's end of support and the difficulties faced by users running legacy software. Additionally, the author provides tips for setting up local accounts on Windows 11 and shares their experience with repairing a Surface Pro device. [Extracted from the article]

Published
2024

16. "The customer is welcome to buy whatever they wish, but I like to investigate their expectations".

Author

GRANT, LEE

Subjects
STREAMING technology, CONSUMERS, LACTOSE, COPPER, MANUFACTURING industries
Abstract

The article discusses various aspects of PC cooling and repair. It highlights the popularity of the Kraken Elite RGB 360 liquid CPU cooler and the challenges of retrofitting it into an existing machine. The author emphasizes the importance of understanding customer expectations and managing them effectively. The article also discusses the risks of leaking AIO coolers and recommends alternative cooling solutions, such as air coolers like the Be Quiet Dark Rock Pro 5. Additionally, the author shares insights on laptop repair, including the use of adhesives like J-B Weld's PlasticWeld for plastic repairs. The article concludes with a mention of Teclast's innovative approach to keyboard stickers. [Extracted from the article]

Published
2024

17. Host seeking parasitic nematodes use specific odors to assess host resources

Author

Tiffany Baiocchi, Grant Lee, Dong-Hwan Choe, and Adler R. Dillman

Subjects
Medicine, Science
Abstract

Abstract Entomopathogenic nematodes (EPNs) are insect parasites used as biological control agents. Free-living infective juveniles (IJs) of EPNs employ host-seeking behaviors to locate suitable hosts for infection. We found that EPNs can differentiate between naïve and infected hosts, and that host attractiveness changes over time in a species-specific manner. We used solid-phase microextraction and gas chromatography/mass spectrometry to identify volatile chemical cues that may relay information about a potential host’s infection status and resource availability. Among the chemicals identified from the headspace of infected hosts, 3-Methyl-2-buten-1-ol (prenol) and 3-Hydroxy-2-butanone (AMC) were selected for further behavioral assays due to their temporal correlation with the behavioral changes of IJs towards the infected hosts. Both compounds were repulsive to IJs of Steinernema glaseri and S. riobrave in a dose-dependent manner when applied on an agar substrate. Furthermore, the repulsive effects of prenol were maintained when co-presented with the uninfected host odors, overriding attraction to uninfected hosts. Prenol was attractive to dauers of some free-living nematodes and insect larvae. These data suggest that host-associated chemical cues may have several implications in EPN biology, not only as signals for avoidance and dispersal of conspecifics, but also as attractants for new potential hosts.

Published
2017
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18. Measurement challenge: protocol for international case–control comparison of mammographic measures that predict breast cancer risk

Author

Jennifer Stone, John Shepherd, Giske Ursin, John L Hopper, Chao Wang, Evenda Dench, Daniela Bond-Smith, Ellie Darcey, Grant Lee, Ye K Aung, Ariane Chan, Jack Cuzick, Ze Y Ding, Chris F Evans, Jennifer Harvey, Ralph Highnam, Meng-Kang Hsieh, Despina Kontos, Shuai Li, Shivaani Mariapun, Carolyn Nickson, Tuong L Nguyen, Said Pertuz, Pietro Procopio, Nadia Rajaram, Kathy Repich, Maxine Tan, Soo-Hwang Teo, Nhut Ho Trinh, Isabel dos-Santos-Silva, Valerie McCormack, and Mads Nielsen

Subjects
Medicine
Abstract

Introduction For women of the same age and body mass index, increased mammographic density is one of the strongest predictors of breast cancer risk. There are multiple methods of measuring mammographic density and other features in a mammogram that could potentially be used in a screening setting to identify and target women at high risk of developing breast cancer. However, it is unclear which measurement method provides the strongest predictor of breast cancer risk.Methods and analysis The measurement challenge has been established as an international resource to offer a common set of anonymised mammogram images for measurement and analysis. To date, full field digital mammogram images and core data from 1650 cases and 1929 controls from five countries have been collated. The measurement challenge is an ongoing collaboration and we are continuing to expand the resource to include additional image sets across different populations (from contributors) and to compare additional measurement methods (by challengers). The intended use of the measurement challenge resource is for refinement and validation of new and existing mammographic measurement methods. The measurement challenge resource provides a standardised dataset of mammographic images and core data that enables investigators to directly compare methods of measuring mammographic density or other mammographic features in case/control sets of both raw and processed images, for the purposes of the comparing their predictions of breast cancer risk.Ethics and dissemination Challengers and contributors are required to enter a Research Collaboration Agreement with the University of Melbourne prior to participation in the measurement challenge. The Challenge database of collated data and images are stored in a secure data repository at the University of Melbourne. Ethics approval for the measurement challenge is held at University of Melbourne (HREC ID 0931343.3).

Published
2019
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19. The truth about refurb.

Author

Grant, Lee

Subjects
SPARE parts, XBOX video game consoles, QUALITY control
Abstract

The article discusses the growing industry of refurbished technology and its value for consumers. It highlights the benefits of refurbished tech, such as access to top-tier products at cheaper prices and its contribution to corporate eco-credentials. However, challenges exist in integrating refurb into the circular economy, and the UK still generates a significant amount of electronic waste. Companies like Currys and RD-UK are investing in repair infrastructure and offering warranty-backed refurbished products. Apple's software and bureaucracy pose barriers to refurbishment, but companies like Back Market are innovating within the refurb space to provide a quality experience for customers. The article emphasizes the importance of moving towards a circular economy and provides information on where to find refurbished devices and consumer rights and protections. [Extracted from the article]

Published
2024

21. LEE GRANT: “As many PC Pro readers will attest, the danger to becoming a fixer is that it becomes addictive”.

Author

Grant, Lee

Subjects
GENERATIVE artificial intelligence, SPARE parts, RIGHT to repair movement, SERVER farms (Computer network management), RETAIL industry
Abstract

Microsoft has made the source code for MS-DOS 4.0 available on GitHub, although it is not the commonly remembered version. This release is seen as a valuable historical record, but has no practical use in modern computing. Back Market, a refurbished tech marketplace, aims to build trust in buying refurbished products by providing a similar experience to buying new. They prioritize sustainability and recycling, using optical sorting to separate materials from e-waste and collaborating with sellers to improve practices. Back Market also emphasizes the importance of repair and refurbishment in achieving a circular economy for electronics. [Extracted from the article]

Published
2024

22. "I believe the current implementation of Windows Update is the best it's ever been".

Author

GRANT, LEE

Subjects
USB technology, LASER printers
Abstract

The article discusses various issues and updates related to Microsoft's Windows operating system. It highlights a recent update, KB503484, which introduced USB 4 performance but caused installation problems for some users. The author also praises the current implementation of Windows Update, stating that it is the best it has ever been. The article further discusses another update, KB5034232, which caused issues with BitLocker encryption and required a complex solution from Microsoft. Additionally, the article mentions a problem with Google Chrome's printing feature and a unique issue with a Samsung laser printer. Overall, the article provides insights into the challenges and improvements associated with Windows updates and related technologies. [Extracted from the article]

Published
2024

23. LEE GRANT: “Tendrils of thermal compound hung between bent pins like cobwebs made from porridge”.

Author

Grant, Lee

Subjects
CLEAN rooms, PORRIDGE, ELECTRONICS recycling, CHEMICAL vapor deposition, REMANUFACTURING
Abstract

This article from PC Pro discusses the challenges of recycling technology and the environmental impact of electronic waste. The author shares a story about a customer who damaged their motherboard while attempting to upgrade to Windows 11. The author also includes insights from Mark Miodownik, a professor of materials and society, who explains the difficulties of recycling electronics and the need for a circular economy. The article concludes by urging readers to consider purchasing refurbished products and questioning the necessity of buying new technology. [Extracted from the article]

Published
2024

24. WINDOWS 10: STICK, UPGRADE OR SWITCH?

Author

Grant, Lee, Rawlinson, Nik, Honeyball, Jon, and Winder, Davey

Subjects
CHARITABLE giving, HARDWARE
Abstract

This article provides information on the options available to users of Windows 10 as it approaches its end of life in 2025. The recommended option is to upgrade to Windows 11, but alternative options such as Linux Mint and Tiny11 are also explored. Linux Mint is highlighted as a user-friendly and cost-effective alternative, while Tiny11 is a stripped-down version of Windows 11 that can run on older hardware. The article emphasizes the importance of not discarding old PCs and suggests donating them to organizations that refurbish and distribute them to those in need. It also discusses other options like Ghost Spectre 11, ReviOS, and streaming a Windows desktop using Windows 365. The article concludes by discussing the security implications of continuing to use Windows 10 after its end of support date. [Extracted from the article]

Published
2024

25. HOT HARDWARE OF THE YEAR.

Author

Collins, Barry, Danton, Tim, Graham-Smith, Darien, Grant, Lee, Honeyball, Jon, and Thuama, Rois Ni

Subjects
PRODUCT reviews, PRICES, HARDWARE, ARTIFICIAL intelligence, LAPTOP computers, SMARTPHONES
Abstract

This document is a collection of product recommendations and reviews from the PC Pro podcast. It features a variety of tech products, including smartphones, extended reality glasses, fitness trackers, video camera systems, phone accessories, game kits, routers, speakers, AI tools, portable power stations, tracking devices, laptops, and portable speakers. The recommendations are made by different individuals on the podcast, each offering their own perspective and opinions on the products. The document includes brief descriptions of each product, its price, and the nominator's opinion on whether it is a good choice or not. [Extracted from the article]

Published
2024

26. Windows 10: Stick, upgrade or switch?

Author

GRANT, LEE, HONEYBALL, JON, RAWLINSON, NIK, and WINDER, DAVEY

Subjects
BUSINESS planning
Abstract

The answer is most likely that Microsoft didn't want to: its goal was to ship a feature-rich operating system that was a genuine step up from Windows 10, rather than a minimised working environment. First, Microsoft takes care of all OS updates, security updates and apps, too. Windows 10 is much more sluggish than previous versions of the OS, so ditching Microsoft for a good, user-friendly software option - Ubuntu, Mint, ChromeOS Flex - breathes new life into old kit and keeps them out of landfill. Microsoft, by killing Windows 10 without an upgrade path for old hardware, is condemning millions of machines to a crusher. [Extracted from the article]

Published
2023

32. Readers' comments.

Author

Urquhart, John, Danton, Tim, Smith, Steve, Johnson, Peter, Grant, Lee, Goulimis, Constantine, Thomas, Peter B., Goodyear, Meic, Collins, Barry, Norton, Francis, Barton, Jim, and Honeyball, Jon

Subjects
AWARDS, COMPUTER software, EXCELLENCE, HOPE
Abstract

The article from PC Pro features readers' comments on various technology-related topics. Readers discuss the satisfaction levels of mobile data providers, the compatibility of Microsoft Outlook for Windows with different email systems, the benefits of using a silent PC solution, and issues with video doorbells. Additionally, a reader shares their experience with Windows compatibility and another reader points out a philosophical error in a previous article. The editor responds to each comment with informative and helpful insights. [Extracted from the article]

Published
2025

33. LEE GRANT: “My kids are able to handle tricky situations, even ones inadvertently caused by their own father”.

Author

GRANT, LEE

Subjects
QUESTION & answer websites, ENGINEERS, SUBWAYS
Abstract

The article discusses the author's experience with the Divoom LED Bluetooth speaker and its chat feature, which allows users to share and download designs. The author's children encountered offensive messages from trolls in the chat, and the author reached out to Divoom support for assistance. The article also mentions the importance of teaching children about online safety and the need for parents to be aware of the platforms their children use. Additionally, the article highlights the significance of schematics in repairing electronic devices and the importance of access to manufacturer documentation for repair purposes. [Extracted from the article]

Published
2024

34. LEE GRANT: “Many are convinced they’ve been hacked, scammed or tricked into using rogue software”.

Author

Grant, Lee

Subjects
COMPUTER hacking, COMPUTER software, WEB-based user interfaces, CLOUD storage
Abstract

The article discusses Microsoft's rollout of New Outlook, a replacement for Windows Mail, and the confusion it has caused among users. Many customers have complained about the visual differences between the two apps and have expressed concerns about being hacked or scammed. The article also mentions the coexistence of Outlook 365 and New Outlook, as well as Microsoft's efforts to promote the use of OneDrive for file storage. Additionally, the author shares a low-tech solution to a problem with a heavy gaming display. [Extracted from the article]

Published
2024

35. "In two decades, I have only ever found five faulty CPUs. Was this faulty CPU #6?".

Author

Grant, Lee

Subjects
GREEN light, PERSONAL computers, RANDOM access memory
Abstract

This article from PC Pro recounts the author's experience with a faulty CPU and highlights the challenges of diagnosing and repairing computer issues. The author describes a case where a customer's desktop computer had multiple problems, including crashing during gaming and LED lighting not working. After troubleshooting various hardware components, the author determined that the motherboard and CPU were faulty. Finding a replacement CPU was difficult, but eventually, a new motherboard, CPU, and SSD were installed, resolving the issues. The article also includes a cautionary tale about customers unknowingly purchasing multiple subscriptions for internet security software. The author advises readers to review their own subscriptions to avoid unnecessary expenses. [Extracted from the article]

Published
2024

36. Getting away with e-crime.

Author

Grant, Lee

Subjects
ELECTRONIC funds transfers, CRIME statistics, INTERNET fraud, ECONOMIC crime, FRAUD, COMMERCIAL crimes, TEXT messages
Abstract

Although APP fraud crimes continue to rise, Levi believes it remains a low-priority crime for law enforcement. FEATURES In 2022, the UK's total financial loss to fraud exceeded £1.2 billion, with more than 2.9 million reported cases. A spokesperson for UK Finance told PC Pro how APP fraud differs from unauthorised fraud. "According to the recently published Fraud Strategy, fraud makes up 40% of all crime, with 1% of police resources being dedicated to this area of business.". [Extracted from the article]

Published
2023

39. Horticulture Mechanics Course Outline. Teacher Education Series, Vol. 15, No. 1t.

Author

Pennsylvania State Univ., University Park. Dept. of Agricultural Education. and Grant, Lee P.

Abstract

The document provides 17 outlines of brief instructional units in mechanics, which are intended for incorporation into an existing program of study in ornamental horticulture at the secondary or postsecondary level. To facilitate the flexible use of the outlines, a grid is presented on which seven occupational areas (such as aboriculture, turfgrass maintenance, and greenhouse production) are matched with the appropriate mechanics unit (such as plumbing, hydraulics, tree tools, and irrigation systems). The units involve safety, simple mechanical skills, and the operation and maintenance, but not repair, of equipment, and cover both fall and spring semester work. The statements within units may be expanded into performance (behavior) objectives, which may then be broken down into task or skill units. (Author/AJ)

Published
1974

42. 906Can mammographic density add value to the Gail model in risk-stratifying women in BreastScreen Australia?

Author

Pietro Procopio, Grant Lee, Bruce Mann, Yulia Arzhaeva, Paul A. James, Sarah Carr, Carolyn Nickson, Lisa Devereux, Cameron J. Wellard, and Louiza S. Velentzis

Subjects
medicine.diagnostic_test, Epidemiology, business.industry, Risk management tools, General Medicine, Odds ratio, medicine.disease, Cancer registry, Breast cancer screening, Breast cancer, Cohort, medicine, Risk assessment, business, Demography, Gail Model
Abstract

Background There is significant interest in personalised, risk-based breast cancer screening. This requires high quality risk assessment. The ‘Gail model’ risk assessment tool has been validated on over 40,000 BreastScreen Australia participants. We assess whether adding mammographic density (MD) information improves risk stratification on that cohort. Methods We used questionnaire data, baseline MD readings (using AutoDensity) and linked screening and cancer registry records from 40,158 BreastScreen Australia participants aged 50–69 years (via the lifepool cohort). We investigated incident invasive breast cancer rates by quintiles of Gail model scores, MD, and combinations of Gail and MD. Results Gail scores and MD values were weakly correlated (r≤0.02). Gail and MD were each strong predictors of incident breast cancer, but stronger predictors when used in combination. For example, the odds ratio for incident invasive breast cancer was 3.6 (95%CI 2.5-6.3) for the 17% of women in the upper two quintiles of both Gail and MD scores compared to the 17% of women in the lower two quintiles of both scores. In comparison, the odds ratio for breast cancer between same-size (each 17%) upper and lower groups for Gail score alone was 2.5 (95%CI 1.8-3.4), and for MD 1.9 (95%CI 1.2-2.9). Conclusions Combining Gail and MD categories improves risk stratification on BreastScreen Australia participants, compared to using Gail or MD alone. Key messages While questionnaire data and MD measures are each strong predictors of future invasive breast cancer among BreastScreen Australia participants, risk prediction is stronger when questionnaire and MD measures are combined.

Published
2021
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43. WE'RE ALL GOING ON A BUSMAN'S HOLIDAY!

Author

GRANT, LEE, HALL, GAVIN, LUPTON, HENRY, and HURLEY, DALE

Subjects
AIR traffic control, FLIGHT simulators, SOLID state drives
Published
2023

45. Molecular comparison of interval and screen‐detected breast cancers

Author

Magnus Zethoven, Paul A. James, David L Goode, Pietro Procopio, Na Li, Jia-Min Pang, Stephen B. Fox, Keilly Kuykhoven, Lisa Devereux, G. Bruce Mann, Sherene Loi, Grant Lee, Carolyn Nickson, David J Byrne, Siobhan Hughes, Kylie L. Gorringe, Peter Savas, Ian G. Campbell, Jacquie Connaughton, Tim Semple, Kenji M Fujihara, Simone M Rowley, Tanjina Kader, Kenneth Elder, Hugo Saunders, and Dane Cheasley

Subjects
Adult, 0301 basic medicine, Oncology, medicine.medical_specialty, DNA Copy Number Variations, Victoria, Gene Dosage, Breast Neoplasms, Gene mutation, Germline, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, Breast cancer, Mutation Rate, Predictive Value of Tests, Internal medicine, Biomarkers, Tumor, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, Prospective Studies, Registries, Family history, skin and connective tissue diseases, Prospective cohort study, Early Detection of Cancer, Germ-Line Mutation, Aged, Aged, 80 and over, business.industry, Cancer, Middle Aged, Prognosis, medicine.disease, Phenotype, 030104 developmental biology, 030220 oncology & carcinogenesis, Female, business, Mammography
Abstract

Breast cancer (BC) diagnosed after a negative mammogram but prior to the next screening episode is termed an 'interval BC' (IBC). Understanding the molecular differences between IBC and screen-detected BCs (SDBC) could improve mammographic screening and management options. Therefore, we assessed both germline and somatic genomic aberrations in a prospective cohort. Utilising the Lifepool cohort of >54 000 women attending mammographic screening programs, 930 BC cases with screening status were identified (726 SDBC and 204 IBC). Clinico-pathological and family history information were recorded. Germline and tumour DNA were collected where available and sequenced for BC predisposition and driver gene mutations. Compared to SDBC, IBCs were significantly associated with a younger age at diagnosis and tumour characteristics associated with worse prognosis. Germline DNA assessment of BC cases that developed post-enrolment (276 SDBCs and 77 IBCs) for pathogenic mutations in 12 hereditary BC predisposition genes identified 8 carriers (2.27%). The germline mutation frequency was higher in IBC versus SDBC, although not statistically significant (3.90% versus 1.81%, p = 0.174). Comparing somatic genetic features of IBC and SDBC matched for grade, histological subtype and hormone receptor revealed no significant differences, with the exception of higher homologous recombination deficiency scores in IBC, and copy number changes on chromosome Xq in triple negative SDBCs. Our data demonstrates that while IBCs are clinically more aggressive than SDBC, when matched for confounding clinico-pathological features they do not represent a unique molecular class of invasive BC, but could be a consequence of timing of tumour initiation and mammographic screening. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Published
2019
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47. Variation in the risk of colorectal cancer in families with Lynch syndrome: a retrospective cohort study

Author

Seçil Aksoy, Michael O. Woods, Heinric Williams, Bruno Buecher, Finlay A. Macrae, Lotte N. Krogh, Jay Qiu, Wan K.W. Juhari, Jan T. Lowery, Anne-Marie Gerdes, Magnus von Knebel Doeberitz, Luigi Ricciardiello, Karsten Schulmann, Jose Luis Soto, Kristina Lagerstedt-Robinson, Kiwamu Akagi, Raj Ramesar, Uffe Birk Jensen, Angel Alonso, Robert Hüneburg, Olivier Caron, Michel Longy, Jan Lubinski, Kate Green, Annabel Goodwin, D. Gareth Evans, Julie Wods, Leigha Senter, Matthew F. Kalady, Mark Clendenning, Barbara A. Leggett, Ravindran Ankathil, Swati G. Patel, Julian Barwell, Katherine M. Tucker, Grant Lee, Pascaline Berthet, Dawn M. Nixon, Sonia S. Kupfer, Naohiro Tomita, Susan Parry, Trinidad Caldés, Robert W. Haile, Edenir Inêz Palmero, Karin Alvarez, Cassandra B. Nichols, Mark A. Jenkins, N. Jewel Samadder, Loic LeMarchand, John Burn, Francisco Lopez, Rodney J. Scott, Pierre Laurent-Puig, Julie Arnold, Christina Therkildsen, Hans K. Schackert, Pilar Garre, Reinhard Buettner, Adriana Della Valle, Patricia Esperon, Wolff Schmiegel, Karl Heinimann, Inge Bernstein, Matthias Kloor, Nicoline Hoogerbrugge, Rui Manuel Reis, Fränzel J.B. Van Duijnhoven, Christoph Engel, Mohd Nizam Zahary, Sylviane Olschwang, Sapna Syngal, Valérie Bonadona, Nicholas Pachter, Matilde Navarro, Albert de la Chapelle, Beate Betz, Jukka-Pekka Mecklin, Catherine Noguès, Elena M. Stoffel, Toni T. Seppälä, Chrystelle Colas, Anneke Lucassen, Allan D. Spigelman, Youenn Drouet, Elisa J. Cops, Uri Ladabaum, Steve Thibodeau, Jeffrey N. Weitzel, Fiona Lalloo, Patrick J. Morrison, Maurizio Genuardi, Kohji Tanakaya, Patrick M. Lynch, Frederik J. Hes, William D. Foulkes, Carmen Guillén-Ponce, Jenny von Salomé, Emilia Rogoża-Janiszewska, Andrew Latchford, John L. Hopper, Carrie Snyder, Verónica Barca-Tierno, Gabriela Möslein, Lauren M. Gima, Melissa C. Southey, Paul A. James, Marion Dhooge, Claudia Perne, Steven Gallinger, Heather Hampel, Amanda B. Spurdle, Ingrid Winship, Emmanuelle Fourme, Rish K. Pai, Daniela Turchetti, Marta Pineda, Jürgen Weitz, James Hill, Daniel D. Buchanan, Carlos A. Vaccaro, Noralane M. Lindor, Rachel Pearlman, Pål Møller, Christian P. Strassburg, Jane C. Figueiredo, Aída Falcón de Vargas, Silke Zachariae, Karolin Bucksch, Joanne Ngeow, Silke Redler, Henrik Okkels, Maija R.J. Kohonen-Corish, Hans F. A. Vasen, Verena Steinke-Lange, Roselyne Guimbaud, Deepak Vangala, Isabelle Coupier, Nils Rahner, Berrin Tunca, Sanne W. Bajwa-ten Broeke, Niels de Wind, Sophie Lejeune, José Gaston Guillem, Karin Wadt, Polly A. Newcomb, Elke Holinski-Feder, Florencia Neffa, Rodrigo Santa Cruz Guindalini, Paul E. Wise, Julian R. Sampson, Graham Casey, Lene Juel Rasmussen, Rolf H. Sijmons, Tadeusz Dębniak, Ann-Sofie Backman, Joji Utsunomiya, Melyssa Aronson, Aung Ko Win, Yves-Jean Bignon, Judy W. C. Ho, Robyn L. Ward, Mev Dominguez-Valentin, Karolina Malińska, Elizabeth E. Half, John-Paul Plazzer, Marjolijn J. L. Ligtenberg, Rachel Austin, Nicola K. Poplawski, Marcia Cruz-Correa, Nagahide Matsubara, Charlotte Kvist Lautrup, Thomas Hansen, Tatsuro Yamaguchi, Thomas John, David J. Amor, Ilana Solomon, Yun-Hee Choi, Meghan J. van Wanzeele, Rakefet Shtoyerman, Vanessa Huntley, Maartje Nielsen, Deborah Neklason, Kevin J. Monahan, Gülçin Tezcan, Stefan Aretz, Talya Boisjoli, Sophie Giraud, Thierry Frebourg, Christophe Rosty, Heike Görgens, Lone Sunde, Allyson Templeton, Jacob Nattermann, Mala Pande, Joan Brunet, Nancy Uhrhammer, James M. Church, Florencia Spirandelli, Laurent Briollais, James G. Dowty, Jeanette C. Reece, Rachel Susman, Fay Kastrinos, Kirsi Pylvänäinen, Gabriel Capellá, Helène Schuster, Min H. Chew, Markus Loeffler, Christine Lasset, Michael J. Hall, Capuccine Delnatte, Floor A. Duijkers, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Digital Precision Cancer Medicine (iCAN), ATG - Applied Tumor Genomics, HUS Abdominal Center, Clinical sciences, Medical Genetics, Win A.K., Dowty J.G., Reece J.C., Lee G., Templeton A.S., Plazzer J.-P., Buchanan D.D., Akagi K., Aksoy S., Alonso A., Alvarez K., Amor D.J., Ankathil R., Aretz S., Arnold J.L., Aronson M., Austin R., Backman A.-S., Bajwa-ten Broeke S.W., Barca-Tierno V., Barwell J., Bernstein I., Berthet P., Betz B., Bignon Y.-J., Boisjoli T., Bonadona V., Briollais L., Brunet J., Bucksch K., Buecher B., Buettner R., Burn J., Caldes T., Capella G., Caron O., Casey G., Chew M.H., Choi Y.-H., Church J., Clendenning M., Colas C., Cops E.J., Coupier I., Cruz-Correa M., de la Chapelle A., de Wind N., Debniak T., Della Valle A., Delnatte C., Dhooge M., Dominguez-Valentin M., Drouet Y., Duijkers F.A., Engel C., Esperon P., Evans D.G., Falcon de Vargas A., Figueiredo J.C., Foulkes W., Fourme E., Frebourg T., Gallinger S., Garre P., Genuardi M., Gerdes A.-M., Gima L.M., Giraud S., Goodwin A., Gorgens H., Green K., Guillem J., Guillen-Ponce C., Guimbaud R., Guindalini R.S.C., Half E.E., Hall M.J., Hampel H., Hansen T.V.O., Heinimann K., Hes F.J., Hill J., Ho J.W.C., Holinski-Feder E., Hoogerbrugge N., Huneburg R., Huntley V., James P.A., Jensen U.B., John T., Juhari W.K.W., Kalady M., Kastrinos F., Kloor M., Kohonen-Corish M.R., Krogh L.N., Kupfer S.S., Ladabaum U., Lagerstedt-Robinson K., Lalloo F., Lasset C., Latchford A., Laurent-Puig P., Lautrup C.K., Leggett B.A., Lejeune S., LeMarchand L., Ligtenberg M., Lindor N., Loeffler M., Longy M., Lopez F., Lowery J., Lubinski J., Lucassen A.M., Lynch P.M., Malinska K., Matsubara N., Mecklin J.-P., Moller P., Monahan K., Morrison P.J., Nattermann J., Navarro M., Neffa F., Neklason D., Newcomb P.A., Ngeow J., Nichols C., Nielsen M., Nixon D.M., Nogues C., Okkels H., Olschwang S., Pachter N., Pai R.K., Palmero E.I., Pande M., Parry S., Patel S.G., Pearlman R., Perne C., Pineda M., Poplawski N.K., Pylvanainen K., Qiu J., Rahner N., Ramesar R., Rasmussen L.J., Redler S., Reis R.M., Ricciardiello L., Rogoza-Janiszewska E., Rosty C., Samadder N.J., Sampson J.R., Schackert H.K., Schmiegel W., Schulmann K., Schuster H., Scott R., Senter L., Seppala T.T., Shtoyerman R., Sijmons R.H., Snyder C., Solomon I.B., Soto J.L., Southey M.C., Spigelman A., Spirandelli F., Spurdle A.B., Steinke-Lange V., Stoffel E.M., Strassburg C.P., Sunde L., Susman R., Syngal S., Tanakaya K., Tezcan G., Therkildsen C., Thibodeau S., Tomita N., Tucker K.M., Tunca B., Turchetti D., Uhrhammer N., Utsunomiya J., Vaccaro C., van Duijnhoven F.J.B., van Wanzeele M.J., Vangala D.B., Vasen H.F.A., von Knebel Doeberitz M., von Salome J., Wadt K.A.W., Ward R.L., Weitz J., Weitzel J.N., Williams H., Winship I., Wise P.E., Wods J., Woods M.O., Yamaguchi T., Zachariae S., Zahary M.N., Hopper J.L., Haile R.W., Macrae F.A., Moslein G., and Jenkins M.A.

Subjects
0301 basic medicine, Proband, Oncology, Male, Heredity, DNA mismatch repair, [SDV]Life Sciences [q-bio], SUSCEPTIBILITY, Settore MED/03 - GENETICA MEDICA, 0302 clinical medicine, Residence Characteristics, Risk Factors, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], PMS2, ComputingMilieux_MISCELLANEOUS, MLH1, Age Factors, Middle Aged, Penetrance, Lynch syndrome, 3. Good health, Pedigree, Phenotype, 030220 oncology & carcinogenesis, Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis, Female, Adult, medicine.medical_specialty, PENETRANCE, congenital, hereditary, and neonatal diseases and abnormalities, GENES, 3122 Cancers, colorectal cancer, BREAST, Risk Assessment, 03 medical and health sciences, Sex Factors, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Retrospective Studies, business.industry, MUTATIONS, Cancer, medicine.disease, digestive system diseases, MSH2, MSH6, MODEL, INDIVIDUALS, 030104 developmental biology, Lynch Syndrome, Gene-Environment Interaction, business
Abstract

Findings 5585 families with Lynch syndrome from 22 countries were eligible for the analysis. Of these, there were insufficient numbers to estimate penetrance for Asia and South America, and for those with EPCAM variants. Therefore, we used data (collected between July 11, 2014, and Dec 31, 2018) from 5255 families (1829 MLH1, 2179 MSH2, 798 MSH6, and 449 PMS2), comprising 79 809 relatives, recruited in 15 countries in North America, Europe, and Australasia. There was strong evidence of the existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers (p 0 center dot 0001 for each of the three three continents). These familial risk factors resulted in a wide within-gene variation in the risk of colorectal cancer for men and women from each continent who all carried pathogenic variants in the same gene or the MSH2 c.942+3A T variant. The variation was especially prominent for MLH1 and MSH2 variant carriers, depending on gene, sex and continent, with 7-56% of carriers having a colorectal cancer penetrance of less than 20%, 9-44% having a penetrance of more than 80%, and onlyBackground Existing clinical practice guidelines for carriers of pathogenic variants of DNA mismatch repair genes (Lynch syndrome) are based on the mean age-specific cumulative risk (penetrance) of colorectal cancer for all carriers of pathogenic variants in the same gene. We aimed to estimate the variation in the penetrance of colorectal cancer between carriers of pathogenic variants in the same gene by sex and continent of residence. Methods In this retrospective cohort study, we sourced data from the International Mismatch Repair Consortium, which comprises 273 members from 122 research centres or clinics in 32 countries from six continents who are involved in Lynch syndrome research. Families with at least three members and at least one confirmed carrier of a pathogenic or likely pathogenic variant in a DNA mismatch repair gene (MLH1, MSH2, MSH6, or PMS2) were included. The families of probands with known de-novo pathogenic variants were excluded. Data were collected on the method of ascertainment of the family, sex, carrier status, cancer diagnoses, and ages at the time of pedigree collection and at last contact or death. We used a segregation analysis conditioned on ascertainment to estimate the mean penetrance of colorectal cancer and modelled unmeasured polygenic factors to estimate the variation in penetrance. The existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers was tested by use of a Wald p value for the null hypothesis that the polygenic SD is zero. Findings 5585 families with Lynch syndrome from 22 countries were eligible for the analysis. Of these, there were insufficient numbers to estimate penetrance for Asia and South America, and for those with EPCAM variants. Therefore, we used data (collected between July 11, 2014, and Dec 31, 2018) from 5255 families (1829 MLH1, 2179 MSH2, 798 MSH6, and 449 PMS2), comprising 79 809 relatives, recruited in 15 countries in North America, Europe, and Australasia. There was strong evidence of the existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers (pT variant. The variation was especially prominent for MLH1 and MSH2 variant carriers, depending on gene, sex and continent, with 7-56% of carriers having a colorectal cancer penetrance of less than 20%, 9-44% having a penetrance of more than 80%, and only 10-19% having a penetrance of 40-60%. Interpretation Our study findings highlight the important role of risk modifiers, which could lead to personalised risk assessments for precision prevention and early detection of colorectal cancer for people with Lynch syndrome. Funding National Health and Medical Research Council, Australia. Copyright (c) 2021 Elsevier Ltd. All rights reserved.Methods In this retrospective cohort study, we sourced data from the International Mismatch Repair Consortium, which comprises 273 members from 122 research centres or clinics in 32 countries from six continents who are involved in Lynch syndrome research. Families with at least three members and at least one confirmed carrier of a pathogenic or likely pathogenic variant in a DNA mismatch repair gene (MLH1, MSH2, MSH6, or PMS2) were included. The families of probands with known de-novo pathogenic variants were excluded. Data were collected on the method of ascertainment of the family, sex, carrier status, cancer diagnoses, and ages at the time of pedigree collection and at last contact or death. We used a segregation analysis conditioned on ascertainment to estimate the mean penetrance of colorectal cancer and modelled unmeasured polygenic factors to estimate the variation in penetrance. The existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers was tested by use of a Wald p value for the null hypothesis that the polygenic SD is zero.

Published
2021
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49. "This is RWC, and if this helps only one reader avoid the same pitfalls, then I'll be delighted".

Author

GRANT, LEE

Subjects
INTERNET telephony, VOICE mail systems
Abstract

The article discusses the author's personal experience with transitioning to VoIP (Voice over Internet Protocol) for their business. They encountered several issues with their broadband provider, Virgin Media Business (VMB), including miscommunication about the installation process and faulty voicemail service. The author emphasizes the importance of asking questions and clarifying details when transitioning to VoIP. The article also briefly mentions the author's experience repairing a Dell laptop and their attendance at FixFest 2023, a conference focused on promoting repair and sustainability. [Extracted from the article]

Published
2024

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