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Abstract Background While frailty is a known predictor of adverse outcomes in older patients, its effect in younger populations is unknown. This prospective observational study was conducted in a tertiary-level mixed ICU to assess the impact of frailty on long-term survival in intensive care patients of different ages. Methods Data on premorbid frailty (Clinical Frailty Score; CFS), severity of illness (the Simplified Acute Physiology Score, third version; SAPS3), limitations of care and outcome were collected in 817 adult ICU patients. Hazard ratios (HR) for death within 180 days after ICU admission were calculated. Unadjusted and adjusted analyses were used to evaluate the association of frailty with outcome in different age groups. Results Patients were classified into predefined age groups (18–49 years (n = 241), 50–64 (n = 188), 65–79 (n = 311) and 80 years or older (n = 77)). The proportion of frail (CFS ≥ 5) patients was 41% (n = 333) in the overall population and increased with each age strata (n = 46 (19%) vs. n = 67 (36%) vs. n = 174 (56%) vs. n = 46 (60%), P < 0.05). Frail patients had higher SAPS3, more treatment restrictions and higher ICU mortality. Frailty was associated with an increased risk of 180-day mortality in all age groups (HR 5.7 (95% CI 2.8–11.4), P < 0.05; 8.0 (4.0–16.2), P < 0.05; 4.1 (2.2–6.6), P < 0.05; 2.4 (1.1–5.0), P = 0.02). The effect remained significant after adjustment for SAPS3, comorbidity and limitations of treatment only in patients aged 50–64 (2.1 (1.1–3.1), P < 0.05). Conclusions Premorbid frailty is common in ICU patients of all ages and was found in 55% of patients aged under 64 years. Frailty was independently associated with mortality only among middle-aged patients, where the risk of death was increased twofold. Our study supports the use of frailty assessment in identifying younger ICU patients at a higher risk of death.

Immune checkpoint inhibitors (ICI) targeting programmed death 1 (PD-1), its ligand (PD-L1), or cytotoxic T-lymphocyte antigen 4 (CTLA-4) have shown promising results against multiple cancers, where they reactivate exhausted T cells primed to eliminate tumor cells. ICI therapies have been particularly successful in hypermutated cancers infiltrated with lymphocytes. However, resistance may appear in tumors evading the immune system through alternative mechanisms than the PD-1/PD-L1 or CTLA-4 pathways. A systematic pan-cancer literature search was conducted to examine the association between alternative immune evasion mechanisms via the antigen presentation machinery (APM) and resistance towards ICI treatments targeting PD-1 (pembrolizumab and nivolumab), PD-L1 (durvalumab, avelumab, and atezolizumab), and CTLA-4 (ipilimumab). The APM proteins included the human leucocyte antigen (HLA) class I, its subunit beta-2 microglobulin (B2M), the transporter associated with antigen processing (TAP) 1, TAP2, and the NOD-like receptor family CARD domain containing 5 (NLRC5). In total, 18 cohort studies (including 21 original study cohorts) containing 966 eligible patients and 9 case studies including 12 patients were reviewed. Defects in the APM significantly predicted poor clinical benefit with an odds ratio (OR) of 0.39 (95% CI 0.24–0.63, p < 0.001). The effect was non-significant, when considering complete and partial responses only (OR = 0.52, 95% CI 0.18–1.47, p = 0.216). In summary, the APM contains important targets for tumorigenic alterations which may explain insensitivity towards ICI therapy.

Part of book: ISBN 978-1-009-10023-6QC 20221219

Abstract Optical flow provides an opportunity to elevate the resolution and sensitivity of deflection sensing in background-oriented schlieren (BOS). Despite extensive relevant literature within the field of computer vision, there is a lack of proper quantification of its abilities and limitations with regard to the state-of-the-art BOS experiments. Thus, this study performs an assessment of accuracy and resolution limits in different flow field scenarios utilizing background patterns generated with random dot and wavelet noise distributions. Accordingly, a synthetic assessment over a theoretically generated Prandtl–Meyer expansion fan is conducted with variations introduced in the background patterns and operational parameters of optical flow. A clear superiority of accuracy and resolvable range of density gradient amplitudes over cross-correlation is demonstrated. Moreover, an experimental assessment of supersonic flow features over multiple wind tunnel models is performed. The influence of experimental constraints, limitations and uncertainties related to the application of optical flow in BOS and its comparative performance against the block-matching counterpart is characterized. Graphical abstract

This paper presents the important role that Higher Education Institutions (HEIs) have for mipymes, which according to their resources and knowledge develop their main financial activities in most cases in an empirical way, which makes it difficult to develop effective actions that can support them in their profitability, growth and permanence in an increasingly changing market, which is why the need for external advice to support them to acquire financial education is highlighted. The work is based on the results of the study in which they participated as a member of the Network of Latin American Studies in Administration and Business, which was applied through an online form and in person, the level of reliability of the entire study was an adequate Cronbach's alpha (α = 0.934). Therefore, in this investigation the benefits that ju stify the collaboration of HEIs with this type of economic entities.

PT. XYZ merupakan perusahaan yang menghasilkan produk nutrisi berkualitas di setiap tahap kehidupan manusia tetapi pada proses pengerjaan aplikasi DCOMS (Digital Co-Manufacturing Operations System) ini perlu adanya instruksi kerja untuk mempermudah suatu alur atau urutan dari langkah yang harus dilaksanakan untuk menyelesaikan sebuah pekerjaan. Tujuan penelitian ini yaitu untuk mengetahui cara mengunakaan aplikasi DCOMS (Digital Co-Manufacturing Operations System). Teknik pengumpulan data yang digunakan terdiri dari tiga langkah: metode wawancara, observasi, dan dokumentasi selama bulan Maret 2022. Hasil analisis (1) menunjukan bahwa aplikasi DCOMS (Digital Co-Manufacturing Operations System) ini memudahkan PT. XYZ untuk melihat pelaporan data yang berkaitan dengan perencanaan produksi, proses produksi, kualitas produksi, raw material, packaging material dan hasil produksi antar bagian dalam perusahaan, serta hubungan dengan distributor dan para outsourcing. (2) pembuatan pada instruksi kerja dan interaksi manusia-komputer pada aplikasi DCOMS (Digital Co-Manufacturing Operations System) juga dapat meningkatkan stok akurasi untuk kedepannya atau jangka waktu panjang dan mempermudah outsourcing dalam menginput data list batch order. (3) Pengembangan sistem informasi ini dapat memudahkan PT. XYZ untuk melihat status data list order dari berbagai rekanan pabrik.Kata kunci; Instruksi Kerja, DCOMS, Interaksi Manusia-Komputer, outsourcing, Sistem Informasi

Septic lung damage is associated with endothelial cell and neutrophil activation. This study examines the role of the E3 ubiquitin ligase midline 1 (Mid1) in abdominal sepsis. Mid1 expression was increased in endothelial cells derived from post-capillary venules in septic mice and TNF-α challenge increased Mid1 levels in endothelial cells in vitro. The siRNA-mediated knockdown of Mid1 decreased TNF-α-induced upregulation of ICAM-1 and neutrophil adhesion to endothelial cells. Moreover, Mid1 silencing reduced leukocyte adhesion in post-capillary venules in septic lungs in vivo. The silencing of Mid1 not only decreased Mid1 expression but also attenuated expression of ICAM-1 in lungs from septic mice. Lastly, TNF-α stimulation decreased PP2Ac levels in endothelial cells in vitro, which was reversed in endothelial cells pretreated with siRNA directed against Mid1. Thus, our novel data show that Mid1 is an important regulator of ICAM-1 expression and neutrophil adhesion in vitro and septic lung injury in vivo. A possible target of Mid1 is PP2Ac in endothelial cells. Targeting the Mid1-PP2Ac axis may be a useful way to reduce pathological lung inflammation in abdominal sepsis.