In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.

[EX Q]: Context: To study the pathophysiological importance of changes in insulin sensitivity and islet function over time for alterations in glucose tolerance in a randomly selected large group of non-diabetic women aged 57-59 years over a 3-year period.', 'At baseline and at the 3-year follow-up, glucose tolerance (WHO 75 g oral glucose), insulin sensitivity (euglycaemic, hyperinsulinaemic clamp) and insulin and glucagon secretion (2 to 5-min responses to 5 g i.v. arginine at fasting, 14 and > 25 mmol/l glucose) were measured.', 'At baseline, women with impaired glucose tolerance (IGT, n = 28) had lower insulin sensitivity (p = 0.048) than normal women (NGT, n = 58). The arginine-induced insulin responses (AIR) were inversely associated with insulin sensitivity (r > or = -0.55, p < 0.001). When related to the 3-year follow-up, the baseline product of AIR at 14 mmol/l glucose times insulin sensitivity, insulin effect index (IE) (r = -0.40, p < 0.001) and the arginine-induced glucagon response at 14 mmol/l glucose (AGR, r = 0.28, p = 0.009) both correlated with follow-up 2-h glucose. In a multiple regression model, baseline 2-h glucose, insulin effect index and arginine-induced glucagon response independently predicted 2-h glucose at follow-up (total r = 0.668, p < 0.001). Furthermore, delta insulin sensitivity (i. e. follow-up minus baseline) correlated with delta insulin secretion (r = -0.30, p = 0.006), whereas delta glucagon secretion correlated with delta2-h glucose (r = 0.30, p = 0.006) over the 3 years. In a multiple regression, alterations in 2-h glucose over the 3 years were independently determined by changes in fasting insulin and glucagon secretion (r = 0.424, p < 0.001).\Question: Is glucose intolerance predicted by low insulin secretion and high glucagon secretion : outcome of a prospective study in postmenopausal Caucasian women?
[EX A]: Low insulin secretion, when judged in relation to insulin sensitivity, and high glucagon secretion, determine glucose tolerance over time in the individual subject. These processes are therefore potential targets for prevention of deterioration in glucose tolerance.

[EX Q]: Context: This study tested the hypothesis that patients with more severe substance use disorders (SUDs) at intake respond better when treated in more structured and intensive settings (i.e. in-patient/residential versus out-patient), whereas patients with less severe SUD problems have similar outcomes regardless of treatment setting.', 'Up to 50 new patients were selected randomly from each of a random and representative sample of 50 Department of Veterans Affairs (VA) SUD treatment programs (total n = 1917 patients), and were followed-up an average of 6.7 months later (n = 1277).', 'Patients completed a brief self-report version of the Addiction Severity Index (ASI) at baseline and at follow-up.', 'In mixed-model regression analyses, baseline substance use severity predicted follow-up substance use severity and there were no main effects of treatment setting. However, interaction effects were found, such that more severe patients experienced better alcohol and drug outcomes following in-patient/residential treatment versus out-patient treatment; on the other hand, patients with lower baseline ASI drug severity had better drug outcomes following out-patient treatment than in-patient treatment. Treatment setting was unrelated to alcohol outcomes in patients with less severe ASI alcohol scores.\Question: Do treatment setting and baseline substance use severity interact to predict patients ' outcomes?
[EX A]: Results provide some support to the matching hypothesis that for patients who have higher levels of substance use severity at intake, treatment in in-patient/residential treatment settings is associated with better outcomes than out-patient treatment. More research needs to be conducted before in-patient/residential settings are further reduced as a part of the SUD continuum of care in the United States.

[EX Q]: Context: Mycobacterium tuberculosis (M. tuberculosis) modulates host immune response, mainly T cell responses for its own survival leading to disease or latent infection. The molecules and mechanisms utilized to accomplish immune subversion by M. tuberculosis are not fully understood. Understanding the molecular mechanism of T cell response to M. tuberculosis is important for development of efficacious vaccine against TB.', 'Here, we investigated effect of M. tuberculosis antigens Ag85A and ESAT-6 on T cell signalling events in CD3/CD28 induced Peripheral blood mononuclear cells (PBMCs) of PPD+ve healthy individuals and pulmonary TB patients. We studied CD3 induced intracellular calcium mobilization in PBMCs of healthy individuals and TB patients by spectrofluorimetry, CD3 and CD28 induced activation of mitogen activated protein kinases (MAPKs) in PBMCs of healthy individuals and TB patients by western blotting and binding of transcription factors NFAT and NFB by Electrophorectic mobility shift assay (EMSA).', 'We observed CD3 triggered modulations in free intracellular calcium concentrations in PPD+ve healthy individuals and pulmonary TB patients after the treatment of M. tuberculosis antigens. As regards the downstream signalling events, phosphorylation of MAPKs, Extracellular signal-regulated kinase 1 and 2 (ERK1/2) and p38 was curtailed by M. tuberculosis antigens in TB patients whereas, in PPD+ve healthy individuals only ERK1/2 phosphorylation was inhibited. Besides, the terminal signalling events like binding of transcription factors NFAT and NFB was also altered by M. tuberculosis antigens. Altogether, our results suggest that M. tuberculosis antigens, specifically ESAT-6, interfere with TCR/CD28-induced upstream as well as downstream signalling events which might be responsible for defective IL-2 production which further contributed in T-cell unresponsiveness, implicated in the progression of disease.\Question: Do mycobacterium tuberculosis secretory proteins downregulate T cell activation by interfering with proximal and downstream T cell signalling events?
[EX A]:
To the best of our knowledge, this is the first study to investigate effect of Ag85A and ESAT-6 on TCR- and TCR/CD28- induced upstream and downstream signalling events of T-cell activation in TB patients. This study showed the effect of secretory antigens of M. tuberculosis in the modulation of T cell signalling pathways. This inflection is accomplished by altering the proximal and distal events of signalling cascade which could be involved in T-cell dysfunctioning during the progression of the disease.