Policy strategies for capacity building and scale up of the workforce for comprehensive cancer care: a systematic review.

BACKGROUND: Patients with cancer in low- and middle-income countries experience worse outcomes as a result of the limited capacity of health systems to deliver comprehensive cancer care. The health workforce is a key component of health systems; however, deep gaps exist in the availability and accessibility of cancer care providers. MATERIALS AND METHODS: We carried out a systematic review of the literature evaluating the strategies for capacity building of the cancer workforce. We studied how the policy strategies addressed the availability, accessibility, acceptability, and quality (AAAQ) of the workforce. We used a strategic planning framework (SWOT: strengths, weaknesses, opportunities, threats) to identify actionable areas of capacity building. We contextualized our findings based on the WHO 2030 Global Strategy on Human Resources for Health, evaluating how they can ultimately be framed in a labour market approach and inform strategies to improve the capacity of the workforce (PROSPERO: CRD42020109377). RESULTS: The systematic review of the literature yielded 9617 records, and we selected 45 eligible papers for data extraction. The workforce interventions identified were delivered mostly in the African and American Regions, and in two-thirds of cases, in high-income countries. Many strategies have been shown to increase the number of competent oncology providers. Optimization of the existing workforce through role delegation and digital health interventions was reported as a short- to mid-term solution to optimize cancer care, through quality-oriented, efficiency-improving, and acceptability-enforcing workforce strategies. The increased workload alone was potentially detrimental. The literature on retaining the workforce and reducing brain drain or attrition in underserved areas was commonly limited. CONCLUSIONS: Workforce capacity building is not only a quantitative problem but can also be addressed through quality-oriented, organizational, and managerial solutions of human resources. The delivery of comprehensive, acceptable, and impact-oriented cancer care requires an available, accessible, and competent workforce for comprehensive cancer care. Efficiency-improving strategies may be instrumental for capacity building in resource-constrained settings.

Distribution of the workforce involved in cancer care: a systematic review of the literature.

BACKGROUND: A skilled health workforce is instrumental for the delivery of multidisciplinary cancer care and in turn a critical component of the health systems. There is, however, a paucity of data on the vast inequalities in cancer workforce distribution, globally. The aim of this study is to describe the global distribution and density of the health care workforce involved in multidisciplinary cancer management. METHODS: We carried out a systematic review of the literature to determine ratios of health workers in each occupation involved in cancer care per 100 000 population and per 100 cancer patients (PROSPERO: protocol CRD42018095414). RESULTS: We identified 33 eligible papers; a majority were cross-sectional surveys (n = 16). The analysis of the ratios of health providers per population and per patients revealed deep gaps across the income areas, with gradients of workforce density, highest in high-income countries versus low-income areas. Benchmark estimates of optimal workforce availability were provided in a secondary research analysis: mainly high-income countries reported workforce capacities closer to benchmark estimates. A paucity of literature was defined for critical health providers, including for pediatric oncology, surgical oncology, and cancer nurses. CONCLUSION: The availability and distribution of the cancer workforce is heterogeneous, and wide gaps are described worldwide. This is the first systematic review on this topic. These results can inform policy formulation and modelling for capacity building and scaleup.

Anaplastic lymphoma kinase status in lung cancers: An immunohistochemistry and fluorescence in situ hybridization study from a tertiary cancer center in India.

BACKGROUND AND OBJECTIVES: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) have shown good concordance for the detection of echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (ALK) rearrangement. Since studies reporting FISH/IHC concordance, clinicopathological features, and clinical outcomes of ALK-positive patients from India are lacking, this study was undertaken. MATERIALS AND METHODS: This is a retrospective, observational study of patients with adenocarcinoma of the lung on whom ALK test was performed between March 2013 and December 2015. ALK status was assessed in 341 patients by FISH using Vysis ALK Dual Color Break Apart Rearrangement Probe and IHC using ALK D5F3 clone. Clinicopathological features were noted. Patients were managed as per the standard guidelines. Clinical outcomes - response rate (RR) and progression-free survival (PFS) - were measured. RESULTS: ALK rearrangement was positive in 37 patients (10.9%). ALK positivity was observed more commonly in younger patients with no predilection for any gender or any specific histological subtype. ALK by IHC was highly sensitive (100%), compared to FISH with concordance rate of 94.4%. Thirty one of thirty seven (31 of 37) patients received therapy of which 3 patients received palliative chemotherapy and 28 patients received tyrosine kinase inhibitors (crizotinib/ceritinib). Overall RR observed was 77.4%, and median PFS had not been reached at a median follow-up of 12.5 months. INTERPRETATION AND CONCLUSIONS: We report higher frequency of ALK positivity (10.9%) in patients with adenocarcinoma of the lung. ALK by IHC is more sensitive than FISH for ALK detection with high concordance. These patients had good clinical outcome with TKIs targeting ALK fusion protein.

Effect of operating temperature on performance of microbial fuel cell.

The performance of dual chambered mediator-less microbial fuel cell (MFC) operated under batch mode was evaluated under different operating temperatures, ranging between 20 and 55 degrees C, with step increase in temperature of 5 degrees C. Synthetic wastewater with sucrose as carbon source having chemical oxygen demand (COD) of 519-555 mg/L was used in the study. Temperature was a crucial factor in the performance of MFCs for both COD removal and electricity production. The MFC demonstrated highest COD removal efficiency of 84% and power density normalized to the anode surface area of 34.38 mW/m2 at operating temperature of 40 degrees C. Higher VSS to SS ratio was observed at the operating temperature between 35 and 45 degrees C. Under different operating temperatures the observed sludge yield was in the range of 0.05 to 0.14 g VSS/g COD removed. The maximum Coulombic and energy efficiencies were obtained at 40 degrees C, with values of 7.39 and 13.14%, respectively. Internal resistance of the MFC decreased with increase in operating temperature. Maximum internal resistance of 1,150 omega was observed when the MFC was operated at 20 degrees C; whereas the minimum internal resistance (552 omega) was observed at 55 degrees C.

Study of supercooled orientationally disordered binary solid solutions II: cyclohexyl derivatives, neopentanol and neopentylglycol.

The main aim of the present investigation is to see how various relaxation processes including the chair-chair transformation (as found by earlier researchers at room temperature in mechanical relaxation spectroscopy) in cyclohexane derivatives evolve as the temperature is lowered. For this purpose, four remarkable (two-component) solid solutions that are orientationally disordered are investigated, where the first three systems are hydrogen (H-) bonded pairs, and the fourth is a non-H bonded pair. The former group is the two-component system of cyclohexanol (CHXOL) + 2,2-dimethyl-1-propanol or neopentanol (NPOL); cyclohexanol (CHXOL) + cycloheptanol (CHPOL) & neopentanol (NPOL) + neopentylglycol (NPGOL) systems, and the lone non H-bonded pair that has been studied is cyanocyclohexane (CNCH) and cyclohexylchloride (CHC). In all these cases, the liquid mixtures on cooling form orientationally disordered phases which are a solid solution of the corresponding pure phases. The feature is common to all the four systems studied here, but in CHXOL + CHPOL, the phase I of CHXOL beyond x(m) > or = 0.1 only forms a solid solution (designated as S(I')) with the phase I of CHPOL. In CNCH + CHC the solid phase is stable for the concentration range 0 < or = x(m) < or = 0.4 (without transition to any other phase). The above solid phase I (or I') has been investigated at low temperatures and for several concentrations, by means of dielectric spectroscopy and differential scanning calorimetry (DSC). Depending upon the concentration, this phase reveals a glass transition in the temperature range 116-150 K and associated with this is a pronounced relaxation process identifiable with the so called alpha-process. The dielectric spectra of this process is found to follow the Havriliak-Negami (HN) equation. In context of the binary system study here, the analysis of the various parameters obtained show an isomorphic relationship between the phases of the pure components through a continuous change of parameters. Another process of much smaller magnitude designated as the alpha'-process was also found in systems consisting of cyclohexyl derivatives above the glass transition temperature T(g) which kinetically freezes around 170 K. This process interestingly, is also non-Arrhenius in nature, becomes increasingly weaker with increase in the second component, and may be identified with (axial) chair-(equatorial) chair transformation. In addition in all these systems, a weak high-frequency process and a clear sub-T(g) process, are found which are designated as the beta- & gamma-processes respectively. The beta-process may be identified with Johari-Goldstein (JG) or beta(JG) process as it is found to follow the predictions of the coupling model proposed by Ngai. However, the identification of the gamma-process with internal degrees of freedom are fraught with some problems in the interpretation of the experimental data that are highlighted. The kinetic freezing of the various dielectric processes have been critically examined in relation to the T(g) found in the DSC experiments.

Dielectric and calorimetric investigation of an unusual two-component plastic crystal: cyclohexanol-neopentylglycol.

In the present article, investigations of an unusual two-component (H-) bonded pair, i.e. the cyclohexanol-neopentylglycol system, are reported. The phase I of cyclohexanol (CHXOL) forms a continuous solid solution with the phase I of neopentylglycol (NPGOL). This binary solid solution (S(I)) has been investigated at low temperatures and several concentrations, by means of dielectric spectroscopy and differential scanning calorimetry (DSC). Depending upon the concentration, this phase reveals a glass transition in the temperature range 150-180 K and a pronounced relaxation process identifiable with the so-called primary relaxation process, or alpha-process. The analysis of the various parameters obtained shows an isomorphic relationship between the face-centered cubic phases of both the pure components through a continuous change of parameters. In addition, two sub-T(g) processes (designated as beta-and gamma-) are found. The present observation suggests that the beta-process is probably a Johari-Goldstein relaxation process and the gamma-process is intramolecular in nature. The kinetic freezing of the various dielectric processes has been examined in relation to the T(g) found in the DSC experiments.

Study of secondary relaxation in disordered plastic crystals of isocyanocyclohexane, cyanocyclohexane, and 1-cyanoadamantane.

In the present communication, dielectric relaxation investigations on three interesting supercooled plastic crystalline substances, i.e., isocyanocyclohexane (ICNCH), cyanocyclohexane (CNCH), and 1-cyanoadamantane (CNADM) are reported. All of these have the main dipole moment situated in their side group- C[Triple Bond]N or- N[Triple Bond]C. Differential scanning calorimetry (DSC) was also employed as a supporting technique. Glassy crystal were easily formed in the first two samples by slowly cooling the plastic phase, but in CNADM it was formed by rapidly quenching the room temperature plastic phase. In addition to the so called alpha process that can reasonably be described by a Havriliak-Negami (HN) shape function, a secondary (or beta) relaxation process is found in all the materials. The beta process in CNADM has an activation energy (DeltaE(beta)) of about approximately 13.8+/-1 kJmol, and is present even in the corresponding ordered crystalline phase, i.e., in its monoclinic phase. On the other hand, the magnitude of DeltaE(beta) in both the isomers of cyanocyclohexane, i.e., ICNCH and CNCH, is similar and is about 21.1 and 23.4 kJmol, respectively. Unlike CNADM, the cyclohexane derivatives are capable of exhibiting additional intramolecular process due to chair-chair conversion (i.e., in addition to the rotational motion of the side group- C[Triple Bond]N or- N[Triple Bond]C). Therefore, the secondary process of these systems is compared to that occuring in the binary liquid glass formed by dispersing a small quantity of these dipolar liquids in nearly nonpolar orthoterphenyl (OTP). Measurements were also made in the supercooled binary mixures of other cyclohexyl derivatives like cyclohexylchloride and cyclohexylbromide with OTP which lack a flexible side group. The sub-T(g) relaxation process exhibited in all these cases have almost similar activation energy as in case of pure ICNCH and CNCH. These observations together with the fact that the activation energy for this process is much below that of chair-chair conversion which is about 43 kJmol leads us to the conclusion that sub-T(g) relaxation process in the binary mixtures is JG type, and perhaps beta relaxation process in phase I of ICNCH and CNCH is also similar. With the help of semiemperical calculations of the dipolemoments for the axial and equitorial confirmers, it is concluded that the process associated with the chair-chair may not be dielectrically very active and, hence, should be relatively weaker in magnitude. The beta process in CNADM has an activation energy (DeltaE(beta)) of about 13.8+/-1 kJmol, and is present even in the corresponding ordered crystalline phase indicating that it may not be characteristic of the glass formation of phase I. The molecular structure of CNADM is such that it does not possess other intramolecular degrees of freedom of the type equitorial to axial (or chair-chair) transformation. Our experimental finding that JG relaxation for CNADM dispersed in glassy OTP matrix is about 31 kJmol, indicating that the well resolved sub-T(g) process in CNADM is due to the small side group, i.e., -C[Triple Bond]N and JG relaxation in phase I of CNADM is perhaps not resolvable or too small to be detected.

Dielectric and calorimetric study of orientationally disordered phases in two unusual two-component systems.

In the present communication, investigations of two interesting (two-component) solid solutions are reported where one is a hydrogen (H-)-bonded pair and the other is a non-H-bonded pair. The former is the two-component system cyclooctanol (COOL) + cycloheptanol (CHOL), which forms a simple cubic phase [Rute, M. A.; Salud, J.; Negrier, P.; López, D. O.; Tamarit, J. Ll.; Puertas, R.; Barrio, M.; Mondieig, D. J. Phys. Chem. B 2003, 107, 5914]. This solid phase has been investigated at low temperatures and for several concentrations by means of low-frequency dielectric spectroscopy and differential scanning calorimetry (DSC). Depending upon the concentration, this phase reveals a glass transition in the temperature range of 138-172 K and a pronounced relaxation process identifiable with the so-called alpha process characteristic of a single-component orientationally disordered crystal. The dielectric spectra are found to follow the Havriliak-Negami (HN) equation. The analysis of the various parameters obtained show an isomorphic relationship between the simple cubic phases of both pure components through a continuous change of parameters. In addition, a sub-T(g) process, which is Arrhenius, is found. The kinetic freezing of the various dielectric processes has been critically examined in relation to the T(g) found in the DSC experiments. The non-H-bonded pair that has been studied is cis-1,2-dimethylcyclohexane (DMCH) and cyclohexylchloride (CHC). The liquid mixture of DMCH and CHC upon lowering the temperature forms a solid solution on the DMCH-rich side, which is an orientationally disordered crystal. This phase demonstrates a pronounced alpha process in the dielectric measurements that follows the HN equation. The results are discussed in the context of the solid-liquid phase diagram of this binary system. The observed deviations from Arrhenius and Debye behaviors in the solid solutions studied in this paper are shown to follow the "strong-fragility" pattern of Angell.

Relaxation dynamics of orientationally disordered plastic crystals: effect of dopants.

We have examined the relaxation that occurs in the supercooled plastic crystalline phases of pentachloronitrobenzene (PCNB), dichlorotetramethylbenzene (DCTMB), trichlorotrimethylbenzene (TCTMB) along with some of their deuterated samples, and 1-cyanoadamantane (CNADM) in the presence of intentionally added dopants. The experimental techniques used in the present study are dielectric spectroscopy and differential scanning calorimetry (DSC). Only one relaxation process similar to that of the primary (or alpha-) relaxation characteristic of glass-forming materials is found, but there is no indication of any observable secondary relaxation within the resolution of our experimental setup. The alpha-process can reasonably be described by a Havriliak-Negami (HN) shape function throughout the frequency range. However, in the case of PCNB the dielectric strength (Delta epsilon) of the above said alpha-process does not change appreciably with temperature, though interestingly, a small addition of a dopant such as pentachlorobenzene (PCB), trichlorobenzene (TCB), and chloroadamantane (CLADM) to the molten state of PCNB drastically lowers the dielectric strength by a factor of 4 to 8. Powder X-ray diffraction measurements at room temperature and DSC data do not indicate any appreciable change in the crystalline structure. It is noticed that the effect of PCB as a dopant on the magnitude of alpha-process of CNADM is moderate, whereas both PCB and TCB as dopants show a much reduced effect on the relaxation in DCTMB and TCTMB. It is suggested that the drastic changes in the dielectric strength of the alpha-process is due to the rotational hindrance caused by the presence of a small number of dopant molecules in the host crystalline lattice. In the above context, the possibility of a certain degree of antiparallel ordering of dipoles is also discussed.

Glass transition phenomena in two-component plastic crystals: study of hexasubstituted benzenes.

We have critically examined the relaxation that is known to occur in the crystalline phase of pentachloronitrobenzene (PCNB) and 2,3,4,5,6-pentabromotoluene using dielectric spectroscopy and differential scanning calorimetry (DSC). Within the resolution of our experimental setup, a relaxation process similar to that of the primary (or alpha-) relaxation is found. A slight deviation from Arrhenius behavior is noticed only in the vicinity of the glass transition temperature (T(g)). This deviation and a small steplike change found in the DSC scans at T(g) indicates that the "fragility" of these plastic crystals is rather low. However, in PCNB, the dielectric strength (Deltaepsilon) of the above said alpha-process did not change appreciably with temperature, and, interestingly, a small addition of an impurity such as pentachlorobenzene (PCB) to the molten state of PCNB drastically lowered the dielectric strength and the calorimetric signature of glass transition phenomena in the DSC data at T(g). The room-temperature powder X-ray diffraction measurements in combination with the DSC data in the melting temperature region did not indicate any observable change in the crystalline structure. A residual alpha-process with no significant change in the shape of the dielectric spectrum indicates that the hindrance to the rotational motion of PCNB molecules is caused by the presence of a small number of PCB molecules in the crystalline lattice of PCNB over a certain region. Outside of this region, the original PCNB disordered phase is preserved, which is the origin of the residual alpha-process. With a further increase in PCB concentration, the alpha-process, characteristic of pure PCNB, vanishes, and instead another relaxation develops. This process is explained with the help of a solid-liquid phase diagram of the alpha-process of the plastic phase of 2:1 and 1:2 compound formations, which are stable below 386 +/- 1 and 366 +/- 1 K, respectively.

Dynamics of water in supercooled aqueous solutions of glucose and poly(ethylene glycol)s as studied by dielectric spectroscopy.

The dielectric behaviour of aqueous solutions of glucose, poly(ethylene glycol)s (PEGs) 200 and 600, and poly(vinyl pyrrolidone) (PVP) has been examined at different concentrations in the frequency range of 10(6)-10(-3) Hz by dielectric spectroscopy and by using differential scanning calorimetry down to 77 K from room temperature. The shape of the relaxation spectra and the temperature dependence of the relaxation rates have been critically examined along with temperature dependence of dielectric strength. In addition to the so-called primary (alpha-) relaxation process, which is responsible for the glass-transition event at T(g), another relaxation process of comparable magnitude has been found to bifurcate from the main relaxation process on the water-rich side, which continues to the sub-T(g) region, exhibiting relaxation at low frequencies. The sub-T(g) process dominates the dielectric measurements in aqueous solutions of higher PEGs, and the main relaxation process is seen as a weak process. The sub-T(g) process was not observed when water was replaced by methanol in the binary mixtures. These observations suggest that the sub-T(g) process in the aqueous mixtures is due to the reorientational motion of the 'confined' water molecules. The corresponding dielectric strength shows a noticeable change at T(g), indicating a hindered rotation of water molecules in the glassy phase. The nature of this confined water appears to be anomalous compared to most other supercooled confined liquids.

Sub-Tg relaxations due to dipolar solutes in nonpolar glass-forming solvents.

It is well known that rigid dipolar solutes (in smaller quantity) dispersed in a nonpolar glassy matrix exhibit a sub-T(g) (or beta(s)) relaxation due to the solute often designated as Johari-Goldstein (JG) relaxation, which is intermolecular in nature. In this article, we report the results of our study of such a sub-T(g) process in a wide variety of dipolar solutes in different glassy systems using dielectric spectroscopy over a frequency range of 20-10(6) Hz down to a temperature of 77 K. The T(g) of these solutions are determined using differential scanning calorimetry. The solvents used in this study are o-terphenyl (OTP), isopropylbenzene (IPB), and methylcyclohexane. In the case of rigid molecular solutes, like mono-halogen benzenes, the activation energy (DeltaE(beta)) of the beta(s) process is found to increase with decreasing T(g) of the solvent, with a corresponding decrease in the magnitude of the beta(s) process. In the case of more symmetrical molecular solute, for example, tert-butylchloride, the change in DeltaE(beta) is not very appreciable. These results emphasize the importance of the size of the cage of the host matrix in the relaxation of the solute molecules. We have also studied the sub-T(g) relaxation(s) due to some flexible molecular solutes, viz., 1butylbromide, 1hexylbromide, 1butylacetate, and benzylacetate. These solutes in IPB matrix exhibit only one relaxation, whereas in OTP matrix they exhibit an additional sub-T(g) process, which may be identified with a JG type of relaxation. These observations lead us to the conclusion that the beta process observed in the glassy states of these pure solutes is predominantly intramolecular in nature.

The burden of diabetes and impaired glucose tolerance in India using the WHO 1999 criteria: prevalence of diabetes in India study (PODIS).

This random multistage cross-sectional population survey was undertaken to determine the prevalence of diabetes mellitus (DM) and impaired glucose tolerance (IGT) in subjects aged 25 years and above in India. The study was carried out in 77 centers (40 urban and 37 rural). 18363 (9008 males and 9355 females) subjects were studied. 10617 (5379 males and 5238 females) were from urban areas and 7746 (3629 males and 4117 females) from rural areas. Blood samples were taken after a fast of 10-12 h and 2 h after 75 g of oral glucose. Subjects were categorized as having IGT or DM using the World Health Organisation (WHO) (1999) criteria. The standardized prevalence rate for DM in the total Indian, urban and rural populations was 4.3, 5.9 and 2.7%, respectively. The corresponding IGT rates in the three populations was 5.2, 6.3 and 3.7%, respectively. The urban prevalence of DM and IGT was significantly greater than in the rural population (P < 0.001 in both instances). The prevalence of DM was significantly, more than that of IGT (P < 0.001) within both the rural and urban populations. Type 2 diabetes is a major health problem is India.

The burden of diabetes and impaired fasting glucose in India using the ADA 1997 criteria: prevalence of diabetes in India study (PODIS).

This random multistage cross sectional population survey was undertaken to determine the prevalence of diabetes mellitus (DM) and impaired fasting glycemia/glucose (IFG) in subjects aged 25 years and above in India. The study was carried out in 108 centers (49 urban and 59 rural) to reflect the size and heterogeneity of the Indian population. 41,270 (20,534 males and 20,736 females) subjects were studied. 21,516 (10,865 males and 10,651 females) were from urban areas and 19,754 (9669 males and 10,085 females) from rural areas. Blood samples were taken after a fast of 10-12h and the subjects were categorized as having IFG or DM using the 1997 American Diabetes Association criteria. The age and gender standardized prevalence rate for DM and IFG in the total Indian population was 3.3 and 3.6% respectively (P < 0.001). The standardized prevalence of DM and IFG in urban areas was significantly higher than that for the rural population (urban DM prevalence 4.6% versus rural DM prevalence 1.9%, P < 0.001; urban IFG prevalence 4.8% versus rural IFG prevalence 2.5%, P < 0.001). There was no statistically significant difference in the prevalence between DM (4.6%) and IFG (4.8%) in the urban population. The rural prevalence of IFG (2.5%) was significantly (P <0.001) more than the rural prevalence of DM (1.9%). Type 2 diabetes is a major health problem is India.

Comparing the ADA 1997 and the WHO 1999 criteria: Prevalence of Diabetes in India Study.

This random multistage cross-sectional population survey was undertaken to determine the prevalence of type 2 diabetes mellitus (DM) in subjects aged 25 years and above in India. The study was carried out in 77 centres (42 urban and 35 rural) to reflect the size and heterogeneity of the Indian population. 18,363 (9008 male and 9355 female) subjects were studied. 10,617 (5379 males and 5238 females) were from urban areas and 7746 (3629 males and 4117 females) from rural areas. Blood samples were taken after a fast of 10-12 and 2 h after 75 g of oral glucose. Subjects were categorized as having impaired fasting glycemia (IFG) or DM using the 1997 ADA or having impaired glucose tolerance (IGT) or DM using the 1999 WHO criteria. The age- and gender-standardized prevalence rate for DM using the ADA criteria was 3.6% whilst that using the WHO criteria was 4.3% (P < 0.001). The respective standardized prevalence of DM, using the two criteria was, 4.7 and 5.6%, respectively (P < 0.001) in the urban Indian population and 2.0 and 2.7% (P < 0.02) in the rural Indian population. Using the WHO criteria, 581 subjects were newly diagnosed whilst the ADA criteria newly diagnosed 437 subjects. The respective numbers for the urban population were 425 and 323, and for the rural population were 146 and 114, respectively. The ADA criteria could diagnose 75.2, 76.0 and 73.0% of the subjects who had DM as per the WHO criteria. Of 739 Indian subjects who had IFG, 106 (14.3%) were diagnosed as having DM by the WHO criteria whilst 505 (68.3%) had values compatible with a diagnosis of IGT. Of the 536 urban subjects with IFG, 74 (13.8%) had DM and 350 (65.3%) had IGT using the WHO criteria. Of the 302 rural subjects with IFG, 32 (15.8%) had DM and 155 (76.3%) had IGT using the WHO criteria. 505 (49.9%) of 1012 Indian subjects with IGT as per the WHO criteria had IFG. 350 (47.7%) of 733 urban subjects and 155 (55.5%) of 279 rural subjects with IGT had values compatible with IFG as per the ADA criteria. Type 2 diabetes is a major health problem is India. The use of the ADA criteria would underestimate the prevalence of DM by not diagnosing subjects showing a poor response to a glucose challenge. This along with the discrepancies between subjects showing IGF or IGT could be a challenge to any prevention program.

Bispectral index monitoring in patients undergoing cardiac surgery under cardiopulmonary bypass.

BACKGROUND AND OBJECTIVE: Monitoring the depth of anaesthesia by the bispectral index facilitates the titration of anaesthetic drugs during operation as well as assisting in early recovery. We planned to use this index to control the administration of anaesthetic agents in order to stabilize haemodynamics and promote recovery from anaesthesia in patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: Thirty adult patients undergoing valve replacement or coronary artery grafting under cardiopulmonary bypass were studied in a prospective, randomized, controlled study. Bispectral index monitoring was used in all patients. Patients received isoflurane anaesthesia and boluses of morphine: in the study group, anaesthetic depth was controlled using the bispectral index and clinical variables. In the control group, the bispectral index monitor could not be viewed by the anaesthesiologist. Bispectral index, mean arterial pressure and heart rate were noted every 5 min, and the incidence of hypotension, hypertension, tachycardia and bradycardia also noted. The time to recovery, when patients started obeying commands, was also recorded. RESULTS: Patients in the study group had significantly less hypertension and tachycardia (P < 0.05) than those in the control group. The time to recovery of consciousness was less in the study group than in the control group (n.s., P > 0.05). The bispectral index rose significantly in the control group at the time of institution and termination of cardiopulmonary bypass (P < 0.05). CONCLUSIONS: Anaesthesia controlled by bispectral index monitoring decreases the incidence of haemodynamic disturbances and facilitates titration of anaesthetic agents during cardiopulmonary bypass and thus may assist recovery from anaesthesia.

Absence of post-transcriptional RNA modifications of BCL10 in human malignant mesothelioma and colorectal cancer.

The BCL10 gene, located at 1p22, has been implicated in a number of human malignancies, including malignant mesotheliomas (MMs) and colorectal carcinomas. Subsequent reports, however, have revealed an absence of BCL10 mutations in genomic DNA from such tumors. It has been proposed that some abnormalities of this gene may be found only in RNA and not in genomic DNA, suggesting that BCL10 may be mutated post-transcriptionally, rather than at the genomic level. To explore this possibility, we performed SSCP mutation analysis and direct sequencing of cDNA from 17 MM cell lines displaying LOH in 1p22, 12 MM tumor specimens, and 11 colon carcinoma cell lines. SSCP revealed several different band shifts in these samples. The nucleotide changes observed in the cDNA samples were also seen in matched genomic DNA and corresponded to known polymorphisms in the general population. Thus, we conclude the BCL10 mutations are absent at the cDNA level, and that this gene does not undergo "molecular misreading." Since BCL10 also does not possess mutations at the genomic DNA level, it can be ruled out as a gene involved in the pathogenesis of MM and colorectal cancer.

Mapping of AKT3, encoding a member of the Akt/protein kinase B family, to human and rodent chromosomes by fluorescence in situ hybridization.

Previously, a rodent cDNA encoding the third member of the Akt/PKB family of serine/threonine kinases was cloned. We have now cloned the human homolog of this cDNA, and we have used this clone to map the AKT3 gene to human chromosome 1q44 by fluorescence in situ hybridization (FISH). We have also mapped the rodent homologs of AKT3 to rat chromosome 13q24-->q26 and mouse chromosome 1H4-6 by FISH.

Expression of GPC3, an X-linked recessive overgrowth gene, is silenced in malignant mesothelioma.

Gene expression changes in rat asbestos-induced malignant mesothelioma (MM) cells were investigated by differential mRNA display. A mRNA transcript identified by this approach was abundant in normal rat mesothelial cells but not expressed in rat MM cell lines. Northern blot analysis confirmed that this transcript is uniformly silenced in rat MM cell lines and primary tumors. Nucleotide sequence analysis revealed that this transcript is encoded by the rat glypican 3 gene (GPC3), whose human homolog is mutated in the Simpson-Golabi-Behmel overgrowth syndrome. Allelic loss at the GPC3 locus was infrequent (6.9%) in MM cell lines, and no mutations were found. GPC3 transcript levels were markedly decreased in 16 of 18 primary tumors and 17 of 22 human MM cell lines. Most of the cell lines were shown to have aberrant methylation of the GPC3 promoter region. In two of four human MM cell lines tested, GPC3 expression was restored after 2-deoxy 5-azacytidine (DAC)-mediated demethylation of its promoter region. Ectopic expression of GPC3 inhibited in vitro colony formation of human MM cells. Collectively, these data suggest that down-regulation of GPC3 is a common occurrence in MM and that GPC3, an X-linked recessive overgrowth gene, may encode a negative regulator of mesothelial cell growth.

Comparison of the Effects of Sevoflurane and Halothane on Arterial Oxygenation during One Lung Ventilation.

We investigated the effect of halothane and sevoflurane on oxygenation during one lung ventilation (OLV) in 24 patients undergoing elective thoracic procedures. After induction with thiopentone, 4-5 mg/kg and morphine 0.1 mg/kg, suxamethonium 2mg/kg was administered to facilitate tracheal intubation with a double lumen tube. Anaesthesia was maintained with 1.5-3% sevolurane (group 1, n = 12) or 1.1.5% halothane (group 2, n = 12) in 02 with N20 (1:1) and pancuronium bromide. Arterial blood gases were recorded before surgery in the lateral position with two lung ventilation (2LV), 10, 20 and 30 minutes after beginning of one lung ventilation. Morphine and endtidal inhalational anaesthetic concentration were titrated to desired anaesthetic depth and haemodynamic variables. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and central venous pressure (CVP) were measured during the study period. In both the groups there was a significant decrease of PaO2 apparent at 10 minutes after initiation of OLV. Thereafter PaO2 remained stable throughout the study period in both the groups. It is concluded that oxygenation did not differ significantly with either sevoflurane or halothane during OLV. It is also concluded that decrease in oxygenation with OLV is complete by 10 minutes of its initiation.