Fed-batch control based upon the measurement of intracellular NADH

A series of experiments demonstrating that on-line measurements of intracellular NADH by culture fluorescence can be used to monitor and control the fermentation process are described. A distinct advantage of intercellular NADH measurements over other monitoring techniques such as pH and dissolved oxygen is that it directly measures real time events occurring within the cell rather than changes in the environment. When coupled with other measurement parameters, it can provide a finer degree of sophistication in process control

Protective Effects of Human and Mouse Soluble Scavenger-Like CD6 Lymphocyte Receptor in a Lethal Model of Polymicrobial Sepsis

Sepsis still constitutes an unmet clinical need, which could benefit from novel adjunctive strategies to conventional antibiotic therapy. The soluble form of the scavenger-like human CD6 lymphocyte receptor (shCD6) binds to key pathogenic components from Gram-positive and -negative bacteria and shows time- and dose-dependent efficacy in mouse models of monobacterial sepsis. The objective of the present work was to demonstrate the effectiveness of infusing mouse and human sCD6 by different systemic routes, either alone or as adjunctive therapy to gold standard antibiotics, in a lethal model of polymicrobial sepsis. To this end, C57BL/6 mice undergoing high-grade septic shock induced by cecal ligation and puncture (CLP; ≥90% lethality) were infused via the intraperitoneal (i.p.) or intravenous (i.v.) route with shCD6 at different doses and time points, either alone or in combination with imipenem/cilastatin (I/C) at a dose of 33 mg/kg of body weight every 8 h. Significantly reduced mortality and proinflammatory cytokine levels were observed by i.p. infusion of a single shCD6 dose (1.25 mg/kg) 1 h pre- or post-CLP. When using the i.v. route, mice survival was significantly extended by starting shCD6 infusion at later time points post-CLP (up to 6 h after CLP). Significant adjunctive effects on mouse survival were observed by i.p. or i.v. infusion of shCD6 in combination with i.p. I/C post-CLP. Similar results were obtained in mice expressing high sustained levels (5 to 10 μg/ml) of mouse sCD6 in serum by means of transduction with hepatotropic adeno-associated virus (AAV). Taken together, the data support the conserved antibacterial effects of human and mouse sCD6 and their use as adjunctive therapy in experimental models of complex and severe polymicrobial sepsis.Ministerio de Economía y Competitividad (España) SAF2013-46151-R PCIN-2015-070Instituto de Salud Carlos III RD12/0015/0018European Development Regional Fund RD12/0015/0018Fundació La Marató TV3 201319-30-3

MARK TWAIN\u27S USES OF SUFFERING IN THE WRITER-CHARACTER-READER TRIAD

This thesis studies Mark Twain’s uses of suffering in the writer character reader triad. In the book Huckleberry Finn, Twain himself seems to identify more closely with Huck than he does with Tom, as evidenced by the first person narrative in Finn and the more serious, more carefully developed autobiographical incidents in that book. Perhaps because Twain’s later life was so bleak and unhappy, he poured all of his self-defeat and pessimism into his thoughts for Huck’s old age

\u3cem\u3eNoriega v. Pastrana\u3c/em\u3e: The Supreme Court Takes a Step Back from the Table

The Military Commissions Act of 2006 expressly removed the Geneva Conventions as a source of rights for any person litigating against the United States or its agents. For General Manuel Noriega, the Geneva Conventions provided him with his sole opportunity for relief from what is, in his opinion, a grave injustice; without it, he has no hope of returning to his home country any time in the near future. Thus, Noriega petitioned the Supreme Court and asked the Court to find this restriction to be an unconstitutional suspension of the writ of habeas corpus. To perform this analysis, the Supreme Court would have had to delve into territory previously unexplored and narrowly avoided. Ultimately, the Court declined to accept certiorari, over a strong objection by Justice Thomas, joined by Justice Scalia. This Comment argues that the Supreme Court has avoided the issue long enough, and should have settled the matter once and for all by accepting General Noriega’s challenge

Inherited functional variants of the lymphocyte receptor CD5 influence melanoma survival

Despite the recent progress in treatment options, malignant melanoma remains a deadly disease. Besides therapy, inherited factors might modulate clinical outcome, explaining in part widely varying survival rates. T-cell effector function regulators on antitumor immune responses could also influence survival. CD5, a T-cell receptor inhibitory molecule, contributes to the modulation of antimelanoma immune responses as deduced from genetically modified mouse models. The CD5 SNPs rs2241002 (NM_014207.3:c.671C > T, p.Pro224Leu) and rs2229177 (NM_014207.3:c.1412C > T, p.Ala471Val) constitute an ancestral haplotype (Pro224-Ala471) that confers T-cell hyper-responsiveness and worsens clinical autoimmune outcome. The assessment of these SNPs on survival impact from two melanoma patient cohorts (Barcelona, N = 493 and Essen, N = 215) reveals that p.Ala471 correlates with a better outcome (OR= 0.57, 95% CI = 0.33-0.99, Adj. p = 0.043, in Barcelona OR = 0.63, 95% CI = 0.40-1.01, Adj. p = 0.051, in Essen). While, p.Leu224 was associated with increased melanoma-associated mortality in both cohorts (OR = 1.87, 95% CI = 1.07-3.24, Adj. p = 0.030 in Barcelona and OR = 1.84, 95% CI = 1.04-3.26, Adj. p = 0.037, in Essen). Furthermore survival analyses showed that the Pro224-Ala471 haplotype in homozygosis improved melanoma survival in the entire set of patients (HR = 0.27, 95% CI 0.11-0.67, Adj. p = 0.005). These findings highlight the relevance of genetic variability in immune-related genes for clinical outcome in melanoma

Flourishing Through Contemplative Practices

Our project involves outlining walking, running, and biking routes inside and around Farmville that people can use to not only get more active physically but mentally as well. How this might work is that people can pick up a brochure at the gym, along with possibly a bike, and then choose a route and a contemplative prompt to think about while going along that route. Additionally, we plan to mark good places to stop along the routes to read or just to take a break and continue contemplating the prompt. We will also encourage people to try to do this without their devices so that they are free of distractions and can focus their attention on contemplation. Our goal in doing this is to contribute to the individual flourishing of people within the Farmville community which might cause Farmville as a whole to flourish just a bit more

Stretching the spines of gymnasts: a review

Gymnastics is noted for involving highly specialized strength, power, agility and flexibility. Flexibility is perhaps the single greatest discriminator of gymnastics from other sports. The extreme ranges of motion achieved by gymnasts require long periods of training, often occupying more than a decade. Gymnasts also start training at an early age (particularly female gymnasts), and the effect of gymnastics training on these young athletes is poorly understood. One of the concerns of many gymnastics professionals is the training of the spine in hyperextension-the ubiquitous 'arch' seen in many gymnastics positions and movements. Training in spine hyperextension usually begins in early childhood through performance of a skill known as a back-bend. Does practising a back-bend and other hyperextension exercises harm young gymnasts? Current information on spine stretching among gymnasts indicates that, within reason, spine stretching does not appear to be an unusual threat to gymnasts' health. However, the paucity of information demands that further study be undertaken

Multi-Horizon Glucose Prediction Across Populations with Deep Domain Generalization

Real-time continuous glucose monitoring (CGM), augmented with accurate glucose prediction, offers an effective strategy for maintaining blood glucose levels within a therapeutically appropriate range. This is particularly crucial for individuals with type 1 diabetes (T1D) who require long-term self-management. However, with extensive glycemic variability, developing a prediction algorithm applicable across diverse populations remains a significant challenge. Leveraging meta-learning for domain generalization, we propose GPFormer, a Transformer-based zero-shot learning method designed for multi-horizon glucose prediction. We developed GPFormer on the REPLACE-BG dataset, comprising 226 participants with T1D, and proceeded to evaluate its performance using three external clinical datasets with CGM data. These included the OhioT1DM dataset, a publicly available dataset including 12 T1D participants, as well as two proprietary datasets. The first proprietary dataset included 22 participants, while the second contained 45 participants, encompassing a diverse group with T1D, type 2 diabetes, and those without diabetes, including patients admitted to hospitals. These four datasets include both outpatient and inpatient settings, various intervention strategies, and demographic variability, which effectively reflect real-world scenarios of CGM usage. When compared with a group of machine learning baseline methods, GPFormer consistently demonstrated superior performance and achieved the lowest root mean square error for all the evaluated datasets up to a prediction horizon of two hours. These experimental results highlight the effectiveness and generalizability of the proposed model across a variety of populations, demonstrating its substantial potential to enhance glucose management in a wide range of practical clinical settings

Safety and efficacy of an adaptive bolus calculator for Type 1 diabetes: a randomised control cross over study

Background The Advanced Bolus Calculator for Type 1 Diabetes (ABC4D) is a decision support system employing the artificial intelligence technique of case-based reasoning to adapt and personalise insulin bolus doses. The integrated system comprises a smartphone application and clinical web portal. We aimed to assess safety and efficacy of the ABC4D (intervention) compared to a non-adaptive bolus calculator (control). Methods This was a prospective randomised controlled crossover study. Following a 2-week run-in period, participants were randomised to ABC4D or control for 12 weeks. After a 6-week washout period, participants crossed over for 12 weeks. The primary outcome was difference in percentage (%) time in range (TIR) (3.9-10.0 mmol/L (70-180mg/dL)) change during the daytime (07:00-22:00) between groups. Results 37 adults with type 1 diabetes on multiple daily injections of insulin were randomised, median (IQR) age 44.7 (28.2-55.2) years, diabetes duration 15.0 (9.5-29.0) years, HbA1C 61.0 (58.0-67.0) mmol/mol (7.7 (7.5-8.3)%). Data from 33 participants were analysed. There was no significant difference in daytime %TIR change with ABC4D compared to control (median (IQR) +0.1 (-2.6 to + 4.0)% versus +1.9 (-3.8 to + 10.1)%; p = 0.53). Participants accepted fewer meal dose recommendations in the intervention compared to control (78.7 (55.8-97.6)% versus 93.5 (73.8-100)%; p = 0.009) with a greater reduction in insulin dosage from that recommended. Conclusion The ABC4D is safe for adapting insulin bolus doses and provided the same level of glycaemic control as the non-adaptive bolus calculator. Results suggest that participants did not follow ABC4D recommendations as frequently as control, impacting its effectiveness