Water, environment, and health nexus: understanding the risk factors for waterborne diseases in communities along the Tano River Basin, Ghana.

Freshwater pollution is a major concern in Ghana, directly impacting human health. However, the underlying drivers of exposure and risks are not comprehensively understood, emphasizing the severity and impact of these diseases. This study assessed the interaction between water and human health, specifically focusing on the risk factors for waterborne diseases and the drivers of water pollution among residents near the Tano River Basin, Ghana. A sample size of 400 households was selected from five communities within the basin based on their proximity to the Tano River. In addition, the study combined both spatial and non-spatial data sources to map potential flood zones for the basin. The study found that inadequate sanitation, poor hygiene practices, and contamination from illegal mining were the primary causative factors of waterborne diseases. Additionally, floods and improper waste management significantly contributed to disease outbreaks. The flood susceptibility analysis indicated that areas highly susceptible to flooding cover 21.2% of the basin, predominantly in the southern part. The results highlight the urgent need for comprehensive interventions to address the drivers of waterborne diseases. This study will contribute to the local authorities in developing plans to prevent waterborne diseases and mitigate their economic and public health impacts.

Mosquito electrocuting traps for directly measuring biting rates and host-preferences of Anopheles arabiensis and Anopheles funestus outdoors.

BACKGROUND: Mosquito biting rates and host preferences are crucial determinants of human exposure to vector-borne diseases and the impact of vector control measures. The human landing catch (HLC) is a gold standard method for measuring human exposure to bites, but presents risks to participants by requiring some exposure to mosquito vectors. Mosquito electrocuting traps (METs) represent an exposure-free alternative to HLCs for measuring human exposure to malaria vectors. However, original MET prototypes were too small for measuring whole-body biting rates on humans or large animals like cattle. Here a much larger MET capable of encompassing humans or cattle was designed, and its performance was evaluated relative to both the original small MET and HLC and for quantifying malaria vector host preferences. METHODS: Human landing catch, small human-baited METs (MET-SH), and large METs baited with either a human (MET-LH) or calves (MET-LC) were simultaneously used to capture wild malaria vectors outdoors in rural southern Tanzania. The four capture methods were compared in a Latin-square design over 20 nights. Malaria vector host preferences were estimated through comparison of the number of mosquitoes caught by large METs baited with either humans or cattle. RESULTS: The MET-LH caught more than twice as many Anopheles arabiensis than either the MET-SH or HLC. It also caught higher number of Anopheles funestus sensu lato (s.l.) compared to the MET-SH or HLC. Similar numbers of An. funestus sensu stricto (s.s.) were caught in MET-LH and MET-SH collections. Catches of An. arabiensis with human or cattle-baited large METs were similar, indicating no clear preference for either host. In contrast, An. funestus s.s. exhibited a strong, but incomplete preference for humans. CONCLUSIONS: METs are a sensitive, practical tool for assessing mosquito biting rates and host preferences, and represent a safer alternative to the HLC. Additionally these findings suggest the HLC underestimate whole-body human exposure. MET collections indicated the An. funestus s.s. population in this setting had a higher than expected attack rate on cattle, potentially making eliminating of this species more difficult with human-targetted control measures. Supplementary vector control tools targetted at livestock may be required to effectively tackle this species.

An improved mosquito electrocuting trap that safely reproduces epidemiologically relevant metrics of mosquito human-feeding behaviours as determined by human landing catch.

BACKGROUND: Reliable quantification of mosquito host-seeking behaviours is required to determine the efficacy of vector control methods. For malaria, the gold standard approach remains the risky human landing catch (HLC). Here compare the performance of an improved prototype of the mosquito electrocuting grid trap (MET) as a safer alternative with HLC for measuring malaria vector behaviour in Dar es Salaam, Tanzania. METHODS: Mosquito trapping was conducted at three sites within Dar es Salaam representing a range of urbanicity over a 7-month period (December 2012-July 2013, 168 sampling nights). At each site, sampling was conducted in a block of four houses, with two houses being allocated to HLC and the other to MET on each night of study. Sampling was conducted both indoors and outdoors (from 19:00 to 06:00 each night) at all houses, with trapping method (HLC and MET) being exchanged between pairs of houses at each site using a crossover design. RESULTS: The MET caught significantly more Anopheles gambiae sensu lato than the HLC, both indoors (RR [95 % confidence interval (CI)]) = 1.47 [1.23-1.76], P < 0.0001 and outdoors = 1.38 [1.14-1.67], P < 0.0001). The sensitivity of MET compared with HLC did not detectably change over the course of night for either An. gambiae s.l. (OR [CI]) = 1.01 [0.94-1.02], P = 0.27) or Culex spp. (OR [CI]) = 0.99 [0.99-1.0], P = 0.17) indoors and declined only slightly outdoors: An. gambiae s.l. (OR [CI]) = 0.92 [0.86-0.99], P = 0.04), and Culex spp. (OR [CI]) = 0.99 [0.98-0.99], P = 0.03). MET-based estimates of the proportions of mosquitoes caught indoors (P i ) or during sleeping hours (P fl ), as well as the proportion of human exposure to bites that would otherwise occurs indoors (π i ), were statistically indistinguishable from those based on HLC for An. gambiae s.l. (P = 0.43, 0.07 and 0.48, respectively) and Culex spp. (P = 0.76, 0.24 and 0.55, respectively). CONCLUSIONS: This improved MET prototype is highly sensitive tool that accurately quantifies epidemiologically-relevant metrics of mosquito biting densities, behaviours and human exposure distribution.

Short-term outcome of substance-induced psychotic disorder in a large UK first episode psychosis cohort.

OBJECTIVE: The incidence and outcome of first-episode substance-induced psychotic disorder (SIPD) are unclear. The study aimed to compare the 1-year outcomes of those given a SIPD diagnosis by clinicians compared to other psychosis diagnoses in a first-episode cohort. METHOD: Data were from a large (n = 1027) cohort of first-episode psychosis (FEP) patients admitted to early intervention services in the UK (National EDEN). Diagnosis, including that of SIPD, was made by treating psychiatrists at baseline using ICD10 criteria. Details on symptoms, functioning, quality of life, relapse and recovery were available at baseline and 12 months. RESULTS: There were 67 cases of SIPD (6.5% of the cohort). At baseline, SIPD patients were no different to other psychoses on symptoms, functioning and quality of life. At 12 months, there was no difference in SIPD and other psychoses on functioning, quality of life or relapse and recovery rates. Levels of psychotic and general symptomatology were similar but depressive symptoms were higher in the SIPD group. CONCLUSIONS: First-episode psychosis patients with a diagnosis of SIPD do not appear to have better outcomes than those with other primary psychotic diagnoses. The higher levels of depressive symptoms may be a specific marker in these patients.

Inappropriate prescribing in a large community-dwelling older population: a focus on prevalence and how it relates to patient and physician characteristics.

WHAT IS KNOWN AND OBJECTIVE: The prescription of potentially inappropriate medications (PIMs) for older adults is a well-known population health concern. Updated country-specific estimates of inappropriate prescribing in older adults using germane explicit criteria are needed to facilitate physician-tailored quality improvement strategies. Therefore, we sought to determine the prevalence of PIMs for older adults in Emilia-Romagna, Italy, using the updated Maio criteria. We also evaluated patient and general practitioner (GP) characteristics related to inappropriate prescribing. METHODS: Older adults (≥ 65) in 2012 were evaluated in a one-year retrospective study using administrative health care data. The 2011 Maio criteria includes 25 medications reimbursed by the Italian National Formulary, in the following categories in terms of severity: 16 medications that 'should always be avoided,' 3 that are 'rarely appropriate,' and 6 that have 'some indications although they are often misused.' To evaluate the extent of associations between patient and GP related characteristics, we used generalized estimating equations with an exchangeable covariance design to fit robust logistic regression models. RESULTS AND DISCUSSION: A total of 865,354 older adults were in the cohort and 28% had at least one PIM. Of the entire cohort, 8%, 10%, and 14% of individuals were prescribed at least one medication that 'should always be avoided,' is 'rarely appropriate,' and has 'some indications but are often misused,' respectively. Older patients (≥ 75) and females were more likely to be exposed to PIMs. 2,923 GPs were identified in the region, each having prescribed at least one PIM, of which older GPs (≥ 56), male GPs, and solo practice GPs were more likely to prescribe PIMs to their older patients. WHAT IS NEW AND CONCLUSION: The high prevalence of PIM exposure among older adults is a substantial issue in the region. Knowing how patient and GP characteristics relate to PIMs exposure may improve the design and targeting of initiatives for improving prescribing safety in this population.

Changes in mental state associated with prison environments: a systematic review.

OBJECTIVE: To develop an understanding of the stability of mental health during imprisonment through review of existing research evidence relating physical prison environment to mental state changes in prisoners. METHOD: A systematic literature search was conducted looking at changes in mental state and how this related to various aspects of imprisonment and the prison environment. RESULTS: Fifteen longitudinal studies were found, and from these, three broad themes were delineated: being imprisoned and aspects of the prison regime; stage of imprisonment and duration of sentence; and social density. Reception into prison results in higher levels of psychiatric symptoms that seem to improve over time; otherwise, duration of imprisonment appears to have no significant impact on mental health. Regardless of social density, larger prisons are associated with poorer mental state, as are extremes of social density. CONCLUSION: There are large gaps in the literature relating prison environments to changes in mental state; in particular, high-quality longitudinal studies are needed. Existing research suggests that although entry to prison may be associated with deterioration in mental state, it tends to improve with time. Furthermore, overcrowding, ever more likely as prison populations rise, is likely to place a particular burden on mental health services.

Entomological assessment of hessian fabric transfluthrin vapour emanators for protecting against outdoor-biting Aedes aegypti in coastal Tanzania.

BACKGROUND: A low technology emanator device for slowly releasing vapour of the volatile pyrethroid transfluthrin was recently developed in Tanzania that provides robust protection against night biting Anopheles and Culex vectors of malaria and filariasis for several months. Here these same emanator devices were assessed in Dar es Salaam city, as a means of protection against outdoor-biting Aedes (Stegomia) aegypti, the most important vector of human arboviruses worldwide, in parallel with similar studies in Haiti and Brazil. METHODS: A series of entomological experiments were conducted under field and semi-field conditions, to evaluate whether transfluthrin emanators protect against wild Ae. aegypti, and also compare the transfluthrin responsiveness of Ae. aegypti originating from wild-caught eggs to established pyrethroid-susceptible Ae. aegypti and Anopheles gambiae colonies. Preliminary measurements of transfluthrin vapour concentration in air samples collected near treated emanators were conducted by gas chromatography-mass spectrometry. RESULTS: Two full field experiments with four different emanator designs and three different transfluthrin formulations consistently indicated negligible reduction of human landing rates by wild Ae. aegypti. Under semi-field conditions in large cages, 50 to 60% reductions of landing rates were observed, regardless of which transfluthrin dose, capture method, emanator placement position, or source of mosquitoes (mildly pyrethroid resistant wild caught Ae. aegypti or pyrethroid-susceptible colonies of Ae. aegypti and An. gambiae) was used. Air samples collected immediately downwind from an emanator treated with the highest transfluthrin dose (15g), contained 12 to 19 µg/m3 transfluthrin vapour. CONCLUSIONS: It appears unlikely that the moderate levels of pyrethroid resistance observed in wild Ae. aegypti can explain the modest-to-undetectable levels of protection exhibited. While potential inhalation exposure could be of concern for the highest (15g) dose evaluated, 3g of transfluthrin appears sufficient to achieve the modest levels of protection that were demonstrated entomologically. While the generally low levels of protection against Aedes reported here from Tanzania, and from similar entomological studies in Haiti and Brazil, are discouraging, complementary social science studies in Haiti and Brazil suggest end-users perceive valuable levels of protection against mosquitoes. It therefore remains unclear whether transfluthrin emanators have potential for protecting against Aedes vectors of important human arboviruses.

Flood risk assessment under the shared socioeconomic pathways: a case of electricity bulk supply points in Greater Accra, Ghana.

This study evaluates flood susceptibility and risk on Bulk Supply Points in the Greater Accra region (GAR) using a Frequency Ratio model based on 15 flood conditioning factors. The model explores the influence of natural, meteorological and anthropogenic factors on flooding occurrences under the Shared Socioeconomic Pathway (SSP) scenarios and assesses flood risks at Bulk Supply Points (BSPs). Flood susceptibility mapping was conducted for both current and future periods under various SSP scenarios. Results reveal that elevation, slope, soil type, distance from urban areas, and SPI are the most influential factors contributing to flooding susceptibility in the region. The current flood map, about 37% of the total area of GAR categorized under the moderate flood-susceptible zone category followed by about 30% categorized under the low flood-vulnerable zone. However, about 16% was categorized under the very high flood-vulnerable zone. The study projects increasing flood susceptibility under the SSP scenarios with intensification under SSP2 and SSP3 scenarios. For instance, the areas categorized as high and very high flood susceptibility zones are projected to expand to approximately 32% and 26% each by 2055 under SSP3. The study also assesses flood risks at Bulk Supply Points (BSPs), highlighting the escalating susceptibility of power assets to flooding under different scenarios. For instance, in the very high scenario, flooding is estimated to reach 640 h in 2045 and exceed 800 h in 2055-more than double the 2020 baseline. The analysis shows the bulk supply points face increasing flood susceptibility, with risks escalating most sharply under the severe climate change SSP3 and SSP5 scenarios. Over 75% of BSPs are expected to fall in the low- to medium-risk categories across SSPs while more than 50% of BSPs are within medium- to high-risk categories in all scenarios except SSP1, reflecting the impact of climate change. SSP3 and SSP5 stand out with over 60% of BSPs facing high or very high flooding risks by 2055. It indicates moderate resilience with proper adaptation but highlights potential disruptions in critical infrastructure, such as BSPs, during persistent flooding. The findings of the study are expected to inform Ghana's contributions towards addressing Sustainable Development Goals (SDGs) 7, 11 and 13 in Ghana.

Usefulness of EQ-5D for evaluation of health-related quality of life in young adults with first-episode psychosis.

PURPOSE: To evaluate the psychometric properties of the EQ-5D and the usefulness of this instrument in psychiatric practice as a measure of health-related quality of life (HRQoL) in a sample of young adults with first-episode psychosis. METHODS: The validity of individual questionnaire items is studied using an Item Response/Latent Trait Theory modeling approach. Sensitivity of response patterns on EQ-5D items to particular diagnostic subtypes of psychosis is investigated using a finite mixture modeling approach through latent class analysis. Finally, a structural equation modeling framework is used to study differential item functioning via a multigroup approach. RESULTS: Results suggest that the data closely correspond to the Rasch Rating Scale Model, and therefore that EQ-5D latent scores are equal interval measures. Despite comprising relatively few items, the instrument yields reliable measures of HRQoL for group comparisons and cost-effectiveness evaluation, but EQ-5D score is too imprecise for the assessment of HRQoL for clinical purposes at the individual level. A significant relationship was found between EQ-5D responses and type of psychosis due to inclusion of item anxiety/depression in EQ-5D. Two items (anxiety/depression, functioning in usual activities) showed an ethnicity bias. CONCLUSIONS: Psychometric evidence confirmed the EQ-5D to be a valid, interval measure that is scalable according to Rasch principles.

Impacts of LULC and climate changes on hydropower generation and development: A systematic review.

There is a growing concern on a global scale that the world should transition towards the utilisation of energy-efficient technologies. Hydropower plays a very significant part in the fight against climate change, and as a result, it lessens the impact that climate changewill have on our ability to achieve the Sustainable Development Goals (SDGs). Both the effectiveness of hydropower generation and the amount of streamflow are impacted by climate change as well as land use and land cover (LULC). Accordingly, the purpose of this study is to conduct a literature review on the topic of the past and future effects of climate, land use, and land cover changes on hydropower generation. This review will be based on the entries found in a number of reliable databases. A systematic literature review was carried out to analyse how LULC and climate change will affect hydropower generation and development. The research was based on 158 pieces of relevant literature that had been reviewed by experts and indexed in Scopus, Google Scholar, and ScienceDirect. The review was carried out to determine three goals in mind: the impact of climate change on hydropower generation and development; the impact of climate change on streamflow; and the combined impact of changes in climate and changes in LULC on hydropower. The findings bring to light the primary factors contributing to climate change as well as shifts in LULC which are essential to the generation of hydropower on all scales. The study identifies factors such as precipitation, temperature, floods, and droughts as examples of climate change. Deforestation, afforestation, and urbanisation are identified as the primary causes of changes in LULC over the past several decades. These changes have a negative impact on the generation and development of hydropower.

Hydrologic response to climate change in the Densu River Basin in Ghana.

Climate change continues to pose a threat to the sustainability of water resources. Global warming can have several effects on the water resources and water demands in the Densu River Basin especially household water use and agriculture use among several others. However, the extents to which the hydrology of the Densu River Basin is will be altered in the future remains unknown. In this research, the Water Evaluation and Planning (WEAP21) system was used to study the impacts of future climate change on water resources in the Densu River Basin. Future climate data (rainfall and temperature) for the period 2051-2080 was generated from the Swedish Meteorological and Hydrological Institute's climate models (ICHEC-EC-EARTH and RCA4) for RCP4.5 scenario under CORDEX experiment. The results of the study indicate that the Densu River Basin will experience a temperature increase by 8.23% and a 17% reduction in rainfall resulting in 58.3% reduction in water resources in the area. The climate change impact analysis indicates a reduction in the river streamflow due to decrease in rainfall. It is recommended that future research on climate change adaptation for water management in the Densu River Basin should be conducted.

Mapping suitability for rice production in inland valley landscapes in Benin and Togo using environmental niche modeling.

Inland valleys (IVs) in Africa are important landscapes for rice cultivation and are targeted by national governments to attain self-sufficiency. Yet, there is limited information on the spatial distribution of IVs suitability at the national scale. In the present study, we developed an ensemble model approach to characterize the IVs suitability for rainfed lowland rice using 4 machine learning algorithms based on environmental niche modeling (ENM) with presence-only data and background sample, namely Boosted Regression Tree (BRT), Generalized Linear Model (GLM), Maximum Entropy (MAXNT) and Random Forest (RF). We used a set of predictors that were grouped under climatic variables, agricultural water productivity and soil water content, soil chemical properties, soil physical properties, vegetation cover, and socio-economic variables. The Area Under the Curves (AUC) evaluation metrics for both training and testing were respectively 0.999 and 0.873 for BRT, 0.866 and 0.816 for GLM, 0.948 and 0.861 for MAXENT and 0.911 and 0.878 for RF. Results showed that proximity of inland valleys to roads and urban centers, elevation, soil water holding capacity, bulk density, vegetation index, gross biomass water productivity, precipitation of the wettest quarter, isothermality, annual precipitation, and total phosphorus among others were major predictors of IVs suitability for rainfed lowland rice. Suitable IVs areas were estimated at 155,000-225,000 Ha in Togo and 351,000-406,000 Ha in Benin. We estimated that 53.8% of the suitable IVs area is needed in Togo to attain self-sufficiency in rice while 60.1% of the suitable IVs area is needed in Benin to attain self-sufficiency in rice. These results demonstrated the effectiveness of an ensemble environmental niche modeling approach that combines the strengths of several models.

Treatment with interferon-alpha preferentially reduces the capacity for amplification of granulocyte-macrophage progenitors (CFU-GM) from patients with chronic myeloid leukemia but spares normal CFU-GM.

The biological target for interferon (IFN)-alpha in chronic myeloid leukemia (CML) is unknown, but one possibility is that amplification of granulocyte-macrophage colony-forming cells (CFU-GM) is reduced. Replating CFU-GM colonies and observing secondary colony formation provides a measure of CFU-GM amplification. Amplification of CML, but not normal, CFU-GM in vitro was significantly inhibited by IFN-alpha (P = 0.02). In 5 out of 15 CML cases studied by fluorescence in situ hybridization, in vitro treatment with IFN-alpha increased the proportion of CFU-GM, which lacked BCR-ABL. The ability of patients' CFU-GM to amplify, and suppression of this ability by IFN-alpha, predicted responsiveness to IFN-alpha therapy in 86% of cases. Investigation of patients on treatment with IFN-alpha showed a threefold reduction in CFU-GM amplification in responders (P = 0.03) but no significant change in nonresponders (P = 0.8). We conclude that IFN-alpha preferentially suppresses amplification of CML CFU-GM to varying degrees. The differing in vitro sensitivities to IFN-alpha and growth kinetics of individual patients' cells could help differentiate those who will or will not benefit from treatment with IFN-alpha.

Rapid positive selection of CD34+ cells using magnetic microspheres coated with monoclonal antibody QBEND/10 linked via a cleavable disulphide bond.

Positive selection of CD34+ cells has applications in diagnostic pathology, in peripheral blood and bone marrow transplantation, and in studies on the function and regulation of primitive haemopoietic stem cells. Antibody-coated magnetic microspheres (dynabeads) can be used to isolate these cells by positive selection procedures. However, the advantages of using dynabeads in some positive selection protocols are compromised by the retention of the beads on the cells. We present a protocol which allows the rapid chemical release of the beads from positively sorted cells. The murine immunoglobulin (Ig) G1 CD34 antibody, QBEND/10, was immobilised onto dynabeads as part of a three-layered immune complex: QBEND/10 was attached to F(ab')2 anti-mouse immunoglobulin antibody fragments, which were immunologically bound to a mouse IgG1 myeloma protein. The myeloma protein covalently bonded the triplex to the beads. Thus, disulphide bonds in the hinge region of the F(ab')2 could be reduced with 10 microM dithiothreitol and CD34+ cells released within 20 min. Purified cells can be re-phenotyped by multiple markers and subsets identified. Purity of 97%, recovery of > 50%, and viability over 90% of the CD34+ cells was readily achieved. Furthermore, granulocyte-macrophage colony-forming cells were retained in the positive fraction. This methodology can be used to purify other cell types, including T and B lymphocytes.

Ultrastructural localization of bcl-2 protein.

Previous cell subfractionation studies have indicated that bcl-2 is an inner mitochondrial membrane protein. We have sought to determine the ultrastructural localization of bcl-2 protein in lymphoma and breast carcinoma cell lines and biopsy material known to overexpress bcl-2 using immunoelectron microscopy. To avoid the possibility of processing artifacts, samples were prepared by three different methods: progressive lowering of temperature, cryosectioning, and freeze-substitution. In all instances the labeling of bcl-2 protein was relatively weak but the distribution the same. In both lymphoma and breast carcinoma tissues, bcl-2 protein was detected on the periphery of mitochondria: little labeling of either the mitochondrial matrix or cristae could be detected. Labeling was also detected on the perinuclear membrane and throughout the cytoplasm, as also indicated by confocal microscopy. These data therefore indicate that bcl-2 protein can be detected at several intracellular sites and that at the likely functional destination, the mitochondria, there appears to be, contrary to expectations, a preferential association with the outer membrane.

Identification and characterization of the glucagon receptor from adipose tissue.

125I-glucagon was directly cross-linked to its receptor in isolated adipocyte plasma membranes using a UV irradiation procedure. This investigation resulted in identification of an adipocyte glucagon receptor complex of 62 kDa, present both in white and brown adipose tissues. The specificity of labeling was shown by interference of unlabeled hormone with incorporation of radioactive glucagon into 62 kDa species. Treatment of adipose plasma membranes with N-glycanase resulted in appearance of intermediate species, indicating that the glucagon receptor is modified with several N-linked oligosaccharide chains similarly to the hepatic glucagon receptor. Peptide mapping of the affinity labeled adipose membranes with Staphylococcus aureus V8 protease generated three distinct receptor fragments identical to that of the hepatic receptor. Overall, the biochemical characterization of the rat adipocyte glucagon receptor indicates that it closely resembles the hepatic glucagon receptor.

Extent of variability inherent in measurements of CD34-positive cells in different human haemopoietic tissues.

Estimation of CD34 expression is widely used to detect and quantify progenitor cells in haemopoietic tissues used as stem cell sources for transplantation. Mouse monoclonal antibodies to CD34 recognise different epitopes of the mucin-like sialoglycoprotein. These epitopes can be grouped into three classes by their differing sensitivities to the enzymes: neuraminidase, chymopapain and glycoprotease. We have compared the expression, by flow cytometry, of the three CD34 epitopes on normal adult and fetal haemopoietic tissue and in chronic myeloid leukaemia, and have used four antibodies from each class to assess variability of staining within and between epitope classes. The results reveal variable expression of CD34 both within and between tissue types and antibody classes. As a result of the different levels of detection by different antibodies, the apparent number of CD34-positive cells vary by approximately 6-fold. Enrichment for CD34 cells using magnetic bead technology shows a significant difference in the percentage of CD34 cells detected for two of the epitope types.

Sources of human hematopoietic stem cells for transplantation--a review.

Transplantation of hematopoietic stem cells provides a means of replacing a defective hematopoietic system in patients with a wide range of malignant and nonmalignant disorders that affect the blood forming tissue. The same procedure has also allowed dose-escalation of standard chemotherapy and radiotherapy in the treatment of malignant disease of nonhematological origin. Unit recently, bone marrow has been the sole source of hematopoietic stem cells, but limitations of conventional bone marrow transplantation have stimulated a search for alternative sources and uses of stem cells. Fetal tissues (especially liver) are a recognized source of transplantable stem cells and offer the great advantage of reduced immunogenicity, potentially removing the problems of tissue type matching. Umbilical cord blood is also a rich source of stem cells and, although it contains alloreactive cells, it is readily available without special ethical constraints. Both fetal tissue and cord blood suffer the disadvantages of limited numbers of stem cells per donation, and there is much interest in the development of technologies for the safe and reliable expansion and/or pooling of stem and progenitor cells. The observation that small numbers of stem cells are found in the peripheral blood of adults has led to the exploitation of the blood as a further source of stem cells. The ability to mobilize these cells from the medullary compartment into the periphery by the use of chemotherapy and/or recombinant hematopoietic growth factors has enabled the collection of sufficient numbers of cells for transplantation purposes. All of these advances are increasing the options and the range of choices available to clinicians and patients in the arena of hematopoietic stem cell transplantation.

Correlation of bcl-2 with P-glycoprotein expression in chronic lymphocytic leukaemia and other haematological neoplasms but of neither marker with ex vivo chemosensitivity or patient survival.

We compared bcl-2 with P-glycoprotein expression (C494 and JSB1), and both with ex vivo chemosensitivity by Differential Staining Cytotoxicity (DiSC) assay (25 cytotoxic drugs), in 76 fresh haematological specimens, including 51 chronic lymphocytic leukaemias (CLL). Strong correlations were seen between bcl-2 and Pgp expression in both CLL (r = 0.5; p < 0.001) and AML (r = 0.9; p < 0.001) although bcl-2 expression was only raised in Pgp positive cells. However, there was no correlation between high or low marker levels and either ex vivo drug sensitivity (-0.30 < r < 0.37; p all > 0.1) or patient survival (chi 2 < or = 0.1; p > 0.7). One B-CLL, one PLL and one hairy cell leukaemia were negative for both bcl-2 and Pgp, whilst 3 T-cell specimens were bcl-2 negative but strongly positive for Pgp. These results suggest that the expression of Pgp and bcl-2 may be interlinked and related to immunophenotype and that clinical sensitivity to MDR-inducing and/or apoptosis-inducing drugs is best determined by ex vivo chemosensitivity testing rather than measurement of Pgp or bcl-2 expression.

A light insensitive method for contrast enhancement of insect neurons filled with a cobalt-lysine complex.

Modified protocols for cobalt-filling and silver intensification of neurons in the larval and adult stages of the moth, Manduca sexta, have led to improved neuronal visualization and minimal background staining. In particular, long distance projecting multisegmental interneurons, originating in the pterothoracic or terminal abdominal ganglion, were best visualized when a cobalt:lysine complex was used to fill hemi-connectives for several days at 4 C. Ganglia closest to the placement of tracer, which became flooded with cobalt:lysine during the filling period, were removed from the insect. This step eliminated the artifactual filling of neurons that may have taken up the tracer from such pooled regions. This led to a more accurate assessment of whether a multisegmental interneuron projected through the full length of nerve cord to the original site of tracer placement. The protocol for light insensitive silver intensification of cobalt-filled neurons was modified to include an important pH adjustment. NaOH was used to alter the pH of the protective colloid, sodium tungstate, to 10.4 or greater in solution. Especially in larvae, our techniques produced intensely stained cobalt-filled neurons within ganglia that remained transparent and relatively free of nonspecific silver deposition.