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Management of metabolic disorders involves continuous monitoring of physiology. The growing use of glucose sensors, insulin pumps, and other wearable devices, as well as smartphone-based decision support apps, generates large amounts of real-time data, making diabetes a data-rich domain conducive to digital twin implementation. Mechanistic models of glucose–insulin dynamics have been developed in diabetes research, providing a solid foundation for developing digital twin representations of individual patients' metabolic processes. Artificial intelligence (AI) will play a role in improving the accuracy of digital twin technologies and enable their adaptation and personalization. Case studies have demonstrated that personalized approaches that leverage digital twin technology hold promise for optimizing the management of diabetes by tailoring interventions to individual patients' needs and characteristics. Digital twin technology is emerging as a transformative paradigm for personalized medicine in the management of chronic conditions. In this article, we explore the concept and key characteristics of a digital twin and its applications in chronic non-communicable metabolic disease management, with a focus on diabetes case studies. We cover various types of digital twin models, including mechanistic models based on ODEs, data-driven ML algorithms, and hybrid modeling strategies that combine the strengths of both approaches. We present successful case studies demonstrating the potential of digital twins in improving glucose outcomes for individuals with T1D and T2D, and discuss the benefits and challenges of translating digital twin research applications to clinical practice. [ABSTRACT FROM AUTHOR]

Climate change continues to exacerbate social and economic development challenges in local communities the world over. This paper advances a human development approach to climate resilience innovations, showing how local innovation initiatives can be conduits for increased equity, agency, efficiency and sustainability vis-à-vis effective responses to climate impacts. Based on a scoping review of literature (journal articles, books, theses, occasional papers etc.), and through a discussion of four case studies focused on technological and institutional innovations in selected rural South African communities, a major finding is that local innovation initiatives vis-à-vis livelihoods are laden with opportunities for improved social, economic and ecological well-being. Appreciating and supporting these local innovations will open up viable and transformative pathways towards effectively responding to the impacts of climate change and variability. The paper contributes to an interdisciplinary integration of innovation and climate change research by exploring climate resilience through a transformative human development lens. [ABSTRACT FROM AUTHOR]

Aerobic exercise in type 1 diabetes (T1D) causes rapid increase in glucose utilization due to muscle work during exercise, followed by increased insulin sensitivity after exercise. Better understanding of these changes is necessary for models of exercise in T1D. Twenty-six individuals with T1D underwent three sessions at three insulin rates (100%, 150%, 300% of basal). After 3-h run-in, participants performed 45 min aerobic exercise (moderate or intense). We determined area under the curve for endogenous glucose production (AUCEGP) and rate of glucose disappearance (AUCRd) over 45 min from exercise start. A novel application of linear regression of Rd across the three insulin sessions allowed separation of insulin-mediated from non-insulin-mediated glucose uptake before, during, and after exercise. AUCRd increased 12.45 mmol/L (CI = 10.33–14.58, P < 0.001) and 13.13 mmol/L (CI = 11.01–15.26, P < 0.001) whereas AUCEGP increased 1.66 mmol/L (CI = 1.01–2.31, P < 0.001) and 3.46 mmol/L (CI = 2.81–4.11, P < 0.001) above baseline during moderate and intense exercise, respectively. AUCEGP increased during intense exercise by 2.14 mmol/L (CI = 0.91–3.37, P < 0.001) compared with moderate exercise. There was significant effect of insulin infusion rate on AUCRd equal to 0.06 mmol/L per % above basal rate (CI = 0.05–0.07, P < 0.001). Insulin-mediated glucose uptake rose during exercise and persisted hours afterward, whereas non-insulin-mediated effect was limited to the exercise period. To our knowledge, this method of isolating dynamic insulin- and non-insulin-mediated uptake has not been previously employed during exercise. These results will be useful in informing glucoregulatory models of T1D. The study has been registered at www.clinicaltrials.gov as NCT03090451. NEW & NOTEWORTHY Separating insulin and non-insulin glucose uptake dynamically during exercise in type 1 diabetes has not been done before. We use a multistep process, including a previously described linear regression method, over three insulin infusion sessions, to perform this separation and can graph these components before, during, and after exercise for the first time. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy and feasibility of a dual-hormone (DH) closed-loop system with insulin and a novel liquid stable glucagon formulation compared with an insulin-only closed-loop system and a predictive low glucose suspend (PLGS) system.Research Design and Methods: In a 76-h, randomized, crossover, outpatient study, 23 participants with type 1 diabetes used three modes of the Oregon Artificial Pancreas system: 1) dual-hormone (DH) closed-loop control, 2) insulin-only single-hormone (SH) closed-loop control, and 3) PLGS system. The primary end point was percentage time in hypoglycemia (<70 mg/dL) from the start of in-clinic aerobic exercise (45 min at 60% VO2max) to 4 h after.Results: DH reduced hypoglycemia compared with SH during and after exercise (DH 0.0% [interquartile range 0.0-4.2], SH 8.3% [0.0-12.5], P = 0.025). There was an increased time in hyperglycemia (>180 mg/dL) during and after exercise for DH versus SH (20.8% DH vs. 6.3% SH, P = 0.038). Mean glucose during the entire study duration was DH, 159.2; SH, 151.6; and PLGS, 163.6 mg/dL. Across the entire study duration, DH resulted in 7.5% more time in target range (70-180 mg/dL) compared with the PLGS system (71.0% vs. 63.4%, P = 0.044). For the entire study duration, DH had 28.2% time in hyperglycemia vs. 25.1% for SH (P = 0.044) and 34.7% for PLGS (P = 0.140). Four participants experienced nausea related to glucagon, leading three to withdraw from the study.Conclusions: The glucagon formulation demonstrated feasibility in a closed-loop system. The DH system reduced hypoglycemia during and after exercise, with some increase in hyperglycemia. [ABSTRACT FROM AUTHOR]

In 2018, Lewis and Curry presented a method for estimating the transient climate response (TCR) of the climate system from the temperature change between two time windows: an early baseline period in the nineteenth century and a modern period primarily in the twenty-first century. The results suggest a lower value of TCR than estimates from climate model simulations. Previous studies have identified uncertainty in the historical forcings, the impact of the time evolution of the forcing on temperature response, and observational issues as contributory factors to this disagreement. We investigate a further factor: uncertainty in the bias corrections applied to historical sea surface temperature data. This uncertainty can particularly affect the estimation of variables on decadal time scales and therefore affect the estimation of TCR using the window method as well as estimates of internal variability. We demonstrate that use of the whole historical record can mitigate the impacts of working with short time windows to some extent, particularly with respect to the early part of the record. [ABSTRACT FROM AUTHOR]

This article explores the extent to which South African universities partake in science and innovations designed to raise the living standards of poor rural residents. It concentrates on how well universities have fulfilled their knowledge-production for societal benefit missions in practice, through a comparison of the performance of universities across three relevant initiatives. It contributes to the existing research by showcasing how user-oriented innovation value chains operate and the crucial roles of stakeholders along such chains to optimise benefits for people in resource-poor rural municipalities. Our findings suggest that the science-for-society value chain is non-linear, rather than a straight line as presumed by much of the existing research. As the government department leading South Africa's innovation policy, the Department of Science and Technology has been instrumental in fostering a user-oriented mission among knowledge producers. [ABSTRACT FROM AUTHOR]

This paper presents a multi-physics multi-timescale computational framework for the three-dimensional and two-way coupled fluid-structure-thermal simulation of foil thrust bearings. Individual solvers for the transient fluid flow, structural deformation, heat conduction and the coupling strategy are discussed. Next, heat transfer models of the solid structures within foil thrust bearings are also described in detail. The result is a multi-physics computational framework that can predict the steady state and dynamic performance of foil thrust bearings. Numerical simulations of foil thrust bearings with air and CO 2 are then performed. It is found that the centrifugal pumping that naturally occurs in CO 2 bearings due to the high fluid density provides a new and effective cooling mechanism for the CO 2 bearing. [ABSTRACT FROM AUTHOR]

Paleosols occur in the Driftless Area of southwestern Wisconsin because this area escaped direct Pleistocene glaciation, allowing long-term loess and colluvium accumulation in selected settings. The most complete known depositional sequence at Oil City, Wisconsin, contains eight lithologic units with five paleosols, all with normal remanent magnetism (i.e., <780 ka). Previous work characterized the stratigraphy, pedology, micromorphology, and clay mineralogy of the section. We investigate chemical weathering of the 8–63 µm silt fraction using X-ray diffraction (XRD) and elemental geochemistry by portable X-ray fluorescence (pXRF). Elemental ratios TiO2/CaO, Zr/Sr, and Rb/Sr generally align with the pedological evidence of weathering. Mineral ratios plagioclase/quartz and K-feldspar/quartz display greater scatter and less certainty in interpretation. The paleosols with Bt horizons have ratios indicating greater weathering than the modern soil. The most weathered paleosol is formed in the unnamed fourth loess unit stratigraphically below the Loveland Member. The stratigraphic position and higher degree of weathering support correlation of the fourth loess with the Yarmouth Geosol and Crowley’s Ridge Silt of the Middle Mississippi valley. Geochemical indices by pXRF are more consistent with established lithologic breaks than mineralogy by XRD. Our results support the use of pXRF for stratigraphic and weathering studies of Quaternary sediments. [ABSTRACT FROM AUTHOR]

Objective: Exercise is known to increase the risk for hypoglycemia in type 1 diabetes (T1D) but predicting when it may occur remains a major challenge. The objective of this study was to develop a hypoglycemia prediction model based on a large real-world study of exercise in T1D. Research Design and Methods: Structured study-specified exercise (aerobic, interval, and resistance training videos) and free-living exercise sessions from the T1D Exercise Initiative study were used to build a model for predicting hypoglycemia, a continuous glucose monitoring value <70 mg/dL, during exercise. Repeated measures random forest (RMRF) and repeated measures logistic regression (RMLR) models were constructed to predict hypoglycemia using predictors at the start of exercise and baseline characteristics. Models were evaluated with area under the receiver operating characteristic curve (AUC) and balanced accuracy. Results: RMRF and RMLR had similar AUC (0.833 vs. 0.825, respectively) and both models had a balanced accuracy of 77%. The probability of hypoglycemia was higher for exercise sessions with lower pre-exercise glucose levels, negative pre-exercise glucose rates of change, greater percent time <70 mg/dL in the 24 h before exercise, and greater pre-exercise bolus insulin-on-board (IOB). Free-living aerobic exercises, walking/hiking, and physical labor had the highest probability of hypoglycemia, while structured exercises had the lowest probability of hypoglycemia. Conclusions: RMRF and RMLR accurately predict hypoglycemia during exercise and identify factors that increase the risk of hypoglycemia. Lower glucose, decreasing levels of glucose before exercise, and greater pre-exercise IOB largely predict hypoglycemia risk in adults with T1D. [ABSTRACT FROM AUTHOR]

This study used household data from Taraba State, Nigeria, to explore the advantages of using a multidimensional approach to measure food and nutrition insecurity. Adaptations of three popular food security indicators were combined in a single household questionnaire to test how well the Household Food Insecurity Access Scale (HFIAS), the Dietary Diversity Score (DDS), and the Coping Strategies Index (CSI) complement each other. Sixty-nine per cent of households in the sample were classified as extremely food insecure, which means they are likely to resort to intensive but erosive coping strategies and lower dietary diversity. The three indicators powerfully complemented each other. This multidimensional food security measurement framework provided a more nuanced picture of the depth and breadth of food insecurity for local government areas in Taraba State. This approach can help Nigerian policy authorities overcome the information deficits that impede effective food and nutrition assistance interventions.ABSTRACT FROM PUBLISHER [ABSTRACT FROM AUTHOR]

Soil morphology changes dramatically across the former transition from forest to grassland in the Midwestern U.S.A. That vegetation boundary shifted as a result of Holocene climatic change and fire suppression following Euroamerican settlement, but the timescale of soil response to those vegetation changes and the factors that influence it are poorly known. On steep colluvial slopes of southeastern Minnesota, Mollisols with thick, dark A horizons typically associated with grassland are found today under deciduous forest. Soils with much thinner and/or lighter-colored A horizons occur immediately up- and downslope of the forest-covered Mollisols. Most of the soils with thick A horizons are not in topographic settings found to favor organic matter accumulation in other landscapes. Principal component analysis highlights important axes of textural and mineralogical variation among horizons of these soils, often related to parent material properties. Soils with and without thick A horizons are separated along one principal component heavily loaded by high pH, reflecting the presence of dolomite fragments in the hillslope sediment that soils with thick, dark A horizons formed in. Stable C isotope analysis reveals that the Mollisols with thick, dark A horizons under forest had C input from vegetation with abundant C 4 grasses in the past. Public land survey data also indicate replacement of grassland or savanna by forest since 1854 on colluvial slopes where forest-covered Mollisols occur today. We propose that the soils with thick, dark A horizons under forest today reflect a lagged response to vegetation change, from grassland or savanna to closed forest. Their thick A horizons and some C 4 -derived organic matter may be preserved because dolomite weathering releases abundant Ca ++ and Mg ++ that favor aggregation and organic matter stabilization. Soils with thin A horizons just up- or downslope may also have formed partly under grasses, but have responded more quickly and/or more substantially to vegetation change. [ABSTRACT FROM AUTHOR]

Engine valve train wear protection has been observed despite the absence of classical tribofilm formation. This was found with a lubricant containing zinc dialkyldithiophosphate (ZDDP), despite conventional understanding that ZDDP reduces wear by forming a thick, protective, inorganic phosphate tribofilm. We suggest that an antiwear additive can function by forming non-adherent triboproduct via a mechanically-stimulated chemical reaction. This triboproduct provides antiwear performance while entrained in the contact and is eventually expelled. In a reciprocating sliding tribometer it is observed as a pile of debris on the side of the contact. [ABSTRACT FROM AUTHOR]

Background: Hearing impairment and hearing rehabilitation strategies have historically been studied within the confines of a sound booth under controlled experimental conditions. The real world is quite different from the clinical setting and it is important to study how a person with hearing impairment interacts with the world both with and without a hearing assist intervention. A person's ability to hear enables them to communicate and to effectively interact with the world. If a person suffers from hearing impairment, we might anticipate that they could become more disengaged from the world, more socially isolated, potentially depressed, and have additional comorbidities such as cognitive and physical impairment. Indeed, prior research has shown that hearing impairment is associated with social isolation, decreased functional ability and mobility, fall risk, diabetes, and cognitive impairment. However, nearly all of the work that has been done in this area of assessing the impact of hearing impairment on a person's social, cognitive, and physical health has been done through clinical tests or self-report studies using questionnaires and surveys that attempt to objectively quantify various aspects of health. Unfortunately, clinical tests, questionnaires, and surveys oftentimes inaccurately assess a person's true social, cognitive, and physical health. Only when a person is observed in their natural living environment can a more accurate assessment of health be obtained. The ability to assess hearing health, social engagement, cognitive, and physical health in natural living environments is becoming possible with the advent of ubiquitous sensing capabilities. Purpose: Here we discuss some of the work that has been done by our group and others that may be of use to the field of audiology e-health. The purpose of this article is not to present new experimental data, but rather to describe a new method of using advanced in-home sensing techniques to better understand how hearing diagnostics, interventions, and rehabilitation influence the lives and behaviors of patients. [ABSTRACT FROM AUTHOR]

Automated control of blood glucose in patients with type-1 diabetes has not yet been fully implemented. The aim of this study was to design and clinically evaluate a system that integrates a control algorithm with off-the-shelf subcutaneous sensors and pumps to automate the delivery of the hormones glucagon and insulin in response to continuous glucose sensor measurements. The automated component of the system runs an adaptive proportional derivative control algorithm which determines hormone delivery rates based on the sensed glucose measurements and the meal announcements by the patient. We provide details about the system design and the control algorithm, which incorporates both a fading memory proportional derivative controller (FMPD) and an adaptive system for estimating changing sensitivity to insulin based on a glucoregulatory model of insulin action. For an inpatient study carried out in eight subjects using Dexcom SEVEN PLUS sensors, prestudy HbA1c averaged 7.6, which translates to an estimated average glucose of 171 mg/dL. In contrast, during use of the automated system, after initial stabilization, glucose averaged 145 mg/dL and subjects were kept within the euglycemic range (between 70 and 180 mg/dL) for 73.1% of the time, indicating improved glycemic control. A further study on five additional subjects in which we used a newer and more reliable glucose sensor (Dexcom G4 PLATINUM) and made improvements to the insulin and glucagon pump communication system resulted in elimination of hypoglycemic events. For this G4 study, the system was able to maintain subjects’ glucose levels within the near-euglycemic range for 71.6% of the study duration and the mean venous glucose level was 151 mg/dL. [ABSTRACT FROM PUBLISHER]

Art and others from Berkeley joined the CERN NA49 experiment to prototype STAR technology. Together with Joseph Cerny and Earl Hyde, he used the Bevatron proton beam and novel electronic detectors to discover numerous nuclear isotopes with an extreme imbalance of neutrons and protons, notably lithium-11. , a groundbreaker in exploring extreme states of nuclear matter, died peacefully in his home in Berkeley, California, on 30 June 2021. [Extracted from the article]

Rural localities are often viewed as too remote, sparsely populated and poor in critical resources needed for them to be innovation hubs. This study contributes new evidence on how actor networks improve innovation performance among rural enterprises that are privately owned or are not-for-profit operators. We adopt an exploratory case study method to illustrate the channels of innovation know-how flows, the nature of actor networks, and their contribution to the ways in which new knowledge and practices promote or sustain local rural development.One key finding is that actor networks facilitate access to internal and external innovation know-how among rural enterprises. Another insight suggests that rural private and non-profit enterprises rely on face-to-face interactions with no contractual agreements. Furthermore, non-formal ways of sharing innovative ideas and practices frequently extend to rural actors who are considered to be outside a network. [ABSTRACT FROM PUBLISHER]

The authors discuss the challenges and opportunities associated to the adoption of teleaudiology program in the U.S. Department of Veterans Affairs (VA). They highlight four models of telemedicine practice including synchronous/real-time data collection, remote monitoring, and mobile health. They examine the trends that contribute to the growth in teleaudiology and the opportunity that the technology provides to audiologists and other healthcare providers.

Portability of equipment is an increasingly important component in the practice of audiology. We report on a new device, the OtoID, that supports evidence-based ototoxicity testing protocols, provides capability for hearing testing on the hospital treatment unit, and can automate patient self-testing. The purpose of this article is to report on the validation and verification of the OtoID portable audiometer in 40 subjects both young and old, with and without hearing impairment. Subjects were evaluated by an audiologist using the manual hearing test program and then self-tested via an automated testing program. Testing was done in a sound booth and on a hospital treatment unit. Therefore, data were collected in four conditions (booth vs hospital unit and automated vs manual testing) and analyzed for testing bias, repeatability, and American Speech-Language-Hearing Association-significant ototoxicity false-positive rate. Repeatable hearing threshold results were obtained on all subjects who performed the test, regardless of hearing status or testing location. [ABSTRACT FROM AUTHOR]

Abstract: Major therapeutic advances in the treatment of multiple myeloma (MM) have dramatically improved response rate, remission duration and overall survival. These advances include the introduction of high-dose therapy plus autologous stem cell transplantation in younger patients and, in more recent years, the use of “novel” agents such as Thalidomide, Bortezomib, and Lenalidomide. However, despite this progress, most patient will ultimately relapse and die from resistant disease. The role of maintenance therapy in MM has been investigated for more than 30years, but evidence of clear benefit has only recently emerged. The widely use of novel agents renewed the concept of maintenance or “continuous” treatment, after high dose therapy, as well as after conventional therapy in elderly patients. Recently, a number of randomized studies showed a benefit from maintenance therapy with these agents, including increased response rate, PFS and even OS. [Copyright &y& Elsevier]

Cancer treatment often requires patients to be exposed to drugs that can damage hearing. Drugs such as cisplatin can cause permanent damage to hearing if not detected early. Damage typically occurs first in the more basal regions of the cochlea which are specific for high-frequency (HF) hearing and progresses to more apical regions that are relevant to speech understanding. Monitoring of HF hearing loss can be an effective means for early detection of ototoxicity caused by chemotherapy. Once ototoxicity is detected, the oncology medical team could adjust the drug dosage or switch to medications that are less ototoxic. Telehealth technology may improve access to ototoxicity monitoring. Patients could monitor their own hearing using a device that alerts healthcare professionals in the event of a change in hearing. A portable audiometer is currently not available that is 1) capable of automatic or manual (by an audiologist) operation; 2) designed with precision pure-tone functionality up to 20 kHz; and 3) able to remotely transfer health status information to a healthcare professional. This paper describes the design of a technology, the ototoxicity identification (OtoID), that includes a portable audiometer with HF test functionality that meets ANSI/ASA S3.6-2010 standards and is capable of reliably detecting a person's drug-related hearing changes relative to a baseline period (i.e., before ototoxic drugs) using an automated test. The system includes a wireless cellular modem capable of notifying a remote healthcare professional in the event that a significant change in hearing has occurred in the patient. The system was evaluated on test subjects within a sound-proof booth, a noisy hospital ward, and within their homes. Results indicate that the OtoID system can be used by patients to effectively monitor hearing changes remotely within their home or in a hospital ward, ultimately enabling early detection of ototoxicity and potentially avoiding hearing loss. [ABSTRACT FROM PUBLISHER]

This is the second in our series of clinical articles that discuss everyday presentations. Each emphasises practical aspects of team-based care that are relevant for general practitioners, specialists and paramedical professionals. Disorders arising in blood and bone marrow result in some of the commonest presenting symptoms and signs. A careful history and physical examination, complemented by rational use of laboratory tests, provides the clinical basis for a working diagnosis. If further investigation is needed into bone marrow or plasma, then supplementary imaging and radionuclide technology may be necessary under the guidance of an experienced haematologist. [ABSTRACT FROM AUTHOR]

This article applies the sustainable rural livelihoods approach to purposefully collect and analyse data on how the rural poor live and work in South Africa's West Coast District. The findings offer insights into the livelihoods and needs of rural households and offer vital lessons for pro-poor agrarian reform and rural development policies. Agricultural and non-farm rural households rely on a mix of livelihood sources such as wage employment, agricultural activities and social grants. Livelihood assets are unequally distributed among farmers, farm workers and non-farm rural households. Whereas some land reform beneficiary farmers appear to be accumulating wealth (land, livestock and some financial capital), workers dependent on local agricultural labour markets are trapped in asset poverty. Effective agrarian policies should be grounded in a solid understanding of the land-based livelihood strategies and aspirations of the rural poor. [ABSTRACT FROM PUBLISHER]

This is the first in our third series of clinical vignettes that are centred on everyday presentations. Each emphasises practical aspects of team-based care, having relevance for general practitioners, specialists and paramedical professionals alike. Disorders arising in blood and bone marrow result in some of the commonest symptoms and signs for which patients seek medical advice. A carefully taken history and meticulous physical examination, complemented by thoughtful and judicious use of laboratory tests, provide the clinical basis for a working diagnosis. Advanced haematology may be needed to extend evaluation to the bone marrow and plasma while supplementary imaging or radionuclide technology further links primary care practitioner or specialist to the experienced haematologist. Such a multidisciplinary and fully interactive approach offers the preferred way to problem solving and optimum management. [ABSTRACT FROM AUTHOR]

Abstract: Compared with solid tumor patients, those with hematological malignancies are at particular risk of chemotherapy-induced nausea and vomiting (CINV) because of their young age, exposure to highly-emetogenic induction, consolidation and salvage regimens, the high-dose conditioning regimens used before stem cell transplantation (SCT), and the heavy psychological burden of such treatments. In the absence of prophylaxis, around 75% of patients undergoing SCT experience delayed CINV. With first-generation 5-HT3 receptor antagonists, only about 20% are completely protected from nausea and vomiting, and this frequent and debilitating adverse event has not been fully addressed. In contrast to solid tumors, there are no internationally agreed guidelines for the prevention and treatment of CINV in hematological malignancies. Work on a consensus is urgently required. The second-generation 5-HT3 antagonist palonosetron is highly effective in preventing CINV in patients with solid tumors. The extended half-life of this agent and its mechanisms of action including allosteric binding, positive cooperativity and 5-HT3 receptor internalization, may make it particularly effective in controlling delayed CINV. Although controlled comparisons against first-generation 5HT3 agents have not yet been conducted in the setting of SCT, available evidence suggests that palonosetron may prove beneficial in preventing CINV in high risk patients with hematological malignancies. [Copyright &y& Elsevier]

Abstract: Loess is an important Quaternary sediment that records evidence of landscape instability in sediment source areas and landscape stability in accumulation areas. In Wisconsin, USA loess mantles glaciogenic deposits dating to the last glaciation, but the landscape distribution and effects of the loess mantle on soil formation have received very little attention. This study investigates the influence of glacial landforms on the spatial pattern of loess thickness and how the presence or absence of a loess mantle overlying glaciogenic sediments has influenced soil profile morphology, namely thickness and nature of horizonation. Loess thickness follows systematic trends along hillslopes, with slope percentage explaining most loess thickness variation between summit and backslope positions. In the presence of a loess mantle, solum and Bt horizon thickness is proportional to the thickness of the loess mantle in well-drained profiles. In the absence of a loess mantle, landscape and sediment characteristics that control permeability and water throughflow appear to be the most important determinants of profile characteristics. The loess mantle modulates soil formation above the lithologic discontinuity with sandy calcareous glacial sediments by controlling soil water behavior and having physical and chemical characteristics conducive to transformation to soil genetic horizons. [Copyright &y& Elsevier]

Stimulus-frequency (SF) otoacoustic emission (OAE) amplitude and the amplitude of medial olivocochlear (MOC) inhibition of SF OAEs for ipsilateral, contralateral and bilateral MOC reflex elicitors were recorded in six subjects with type 2 diabetes during a glucose tolerance test (GTT). Five of the six subjects were tested twice for a total of 11 trials and three subjects were tested in a control experiment. During the GTT experiment, the subjects' blood glucose was elevated from a euglycemic level below 150 mg/dL to a hyperglycemic level above 160 mg/dL following the consumption of a bolus of 80 g of sugar. A subset of three subjects were tested in a control experiment during which SF OAE and MOC reflex measurements were made while blood sugar levels remained constant within the euglycemic region. Mean SF OAE amplitudes were elevated following glucose consumption. A statistically significant increase in MOC inhibition amplitude was observed during elevated sugar levels for the 11 GTT trials. Maximum inhibition occurred about an hour after glucose consumption when blood glucose levels peaked. Results indicate that acute hyperglycemia influences efferent control of the cochlea in people with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Traditionally the teaching and management of widely divergent disorders arising primarily in the bone marrow or lymphoreticular system and reflected in the peripheral blood followed, in South Africa, the European tradition, which based the discipline in Pathology rather than Internal Medicine. Countrywide our universities developed undergraduate teaching and postgraduate training along these lines from whence generations of distinguished haematologists established centres of excellence both locally and worldwide. In keeping with a subtle shift to the concept of the clinical scientist and increasing complexity of comprehensive patient treatment, particularly exemplified by the haematologic malignancies where improving outcome favoured emergence of specialised units, the cross-speciality programmes started locally and continue to gather momentum. The University of Cape Town aligned itself with this changing international practice and created a new and autonomous department mandated to develop and fully integrate clinical and laboratory components. The success of the new dispensation culminated in establishment of an experimental immunohaematopoietic stem cell transplantation programme. Over time translational research carried this into the clinic with subsequent dissemination to other centres and eventually into the private sector. Latterly, with changes in health care delivery throughout the country this forward-looking structure was reversed after a successful 25-year period, with a split into two Divisions. Clinical Haematology became part of Internal Medicine and Haematological Pathology now resides within the ambit of the National Health Laboratory Service. From that time little if any significant change has occurred in the state system. However, of interest is the establishment of a university-style department in the private sector that has been consolidated as a satellite within Faculty of Health Sciences at Stellenbosch University and Tygerberg Academic Hospital. This historical record documents the background and various phases that occurred during four decades from 1970 acknowledging the selfless support as well as encouragement of many peers and colleagues, whilst never overlooking the courage of our patients and their families, primarily at Groote Schuur. [ABSTRACT FROM PUBLISHER]

South Africa experienced two waves of rapid food inflation in 2001–02 and 2007–08. During both periods the surge in the cost of food undermined the food-security status of low-income families. Belated state reactions to the food-price crises pay scant attention to the fact that poor net food buyers rely on agro-food markets for their food supplies. Moreover, the touted non-interference of the state in agro-food marketing policy gives the impression that this policy is disconnected from food security. This article challenges that notion. It analyses the content and evolution of agro-food marketing policies and argues the case for food security to be at the core of such policies. [ABSTRACT FROM AUTHOR]

Abstract: Loess has been recognized on the glacial land surface of the Green Bay Lobe for over 100yr, but no systematic explanation of the source of the loess has been advanced. Intriguingly, the loess on the Green Bay Lobe land surface is thicker than predicted by regional thinning trends from the Mississippi Valley and is geographically separated from much loess of southwest Wisconsin by a sandy region devoid of loess. Mapping based on soil survey interpretation indicates that the loess occurs above an escarpment marking the eastern end of the sandy loess-free region. Particle size fining trends demonstrate that the loess was transported by northwesterly winds. Clay mineralogy of the Green Bay Lobe loess is distinctly different than glaciogenic sediments and matches loess of the Mississippi Valley, indicating a regional source and long distance transport of the loess. We propose the loess was transported from the regional source along a surface of transport produced by migration of eolian sand through low-relief landscapes including the glacial Lake Wisconsin basin. Eolian sand migration caused repeated entrainment of dust leading to east-southeastward transport. The loess accumulated above an escarpment that limited sand mobility and re-entrainment of loess beyond this topographic barrier. [Copyright &y& Elsevier]

Abstract: Background: Coronary artery calcium (CAC) and thoracic aorta calcium (TAC) can be detected simultaneously on low-dose, non-gated computed tomography (CT) scans. CAC has been shown to predict cardiovascular (CVD) and coronary (CHD) events. A comparable association between TAC and CVD events has yet to be established, but TAC could be a more reproducible alternative to CAC in low-dose, non-gated CT. This study compared CAC and TAC as independent predictors of all-cause mortality and cardiovascular events in a population of heavy smokers using low-dose, non-gated CT. Methods: Within the NELSON study, a population-based lung cancer screening trial, the CT screen group consisted of 7557 heavy smokers aged 50–75 years. Using a case–cohort study design, CAC and TAC scores were calculated in a total of 958 asymptomatic subjects who were followed up for all-cause death, and CVD, CHD and non-cardiac events (stroke, aortic aneurysm, peripheral arterial occlusive disease). We used Cox proportional-hazard regression to compute hazard ratios (HRs) with adjustment for traditional cardiovascular risk factors. Results: A close association between the prevalence of TAC and increasing levels of CAC was established (p <0.001). Increasing CAC and TAC risk categories were associated with all-cause mortality (p for trend=0.01 and 0.001, respectively) and CVD events (p for trend <0.001 and 0.03, respectively). Compared with the lowest quartile (reference category), multivariate-adjusted HRs across categories of CAC were higher (all-cause mortality, HR: 9.13 for highest quartile; CVD events, HR: 4.46 for highest quartile) than of TAC scores (HR: 5.45 and HR: 2.25, respectively). However, TAC is associated with non-coronary events (HR: 4.69 for highest quartile, p for trend=0.01) and CAC was not (HR: 3.06 for highest quartile, p for trend=0.40). Conclusions: CAC was found to be a stronger predictor than TAC of all-cause mortality and CVD events in a high-risk population of heavy smokers scored on low-dose, non-gated CT. TAC, however, is stronger associated with non-cardiac events than CAC and could prove to be a preferred marker for these events. [Copyright &y& Elsevier]

Abstract: The Farmdale–Sangamon Geosol pedocomplex consists of the Sangamon Geosol and the overlying Farmdale Geosol, which form the most extensive terrestrial record of the last interglacial to glacial transition in the Midwest United States. The geosol complex formed for upwards of 100 ka, extending from the end of MIS 6 through 4 for the Sangamon Geosol, then the Farmdale Geosol for during a brief episode at the end of MIS 3 following slow accumulation and pedogenic modification of eolian silt deposited on top of the Sangamon Geosol. Our study site consists of a buried paleo-hillslope transect that forms a catena, enabling evaluation of slope effects on interglacial-scale soil formation. The Sangamon Geosol is formed in calcareous and illitic glaciogenic sediment. Along the catena the Sangamon Geosol profiles display some morphological changes, namely in terms of colors that we interpret as indicators of differences in drainage. Most thickness and horizonation characteristics are similar all along the transect, with intact upper sola horizons (AE and E horizons) that overlie clay-enriched Bt horizons. The Bt horizons contain abundant clay that exists as illuvial clay coatings, matrix infills, and as mosaic-speckled domains. The clay originated both by in situ weathering and through illuviation from the clay depleted upper sola. Slope does not appear to affect Bt characteristics beyond redder hues of the matrix and clay coatings in the upper slope position. With depth, effects of carbonate leaching and infilling of clay in the matrix decrease and clay coatings are restricted to walls of voids adjacent to aggregates. Clay mineralogy shows illite depletion, but no interstratified kaolinite-expandable minerals, indicating the degree of weathering is not as great as is typical of Sangamon Geosol profiles formed in loess or in glaciogenic sediment of the central Illinois type area. Clay mineralogy is also stratified with depth, coincident with particle size, which probably indicates sorting of layers of illitic dolomite and shale. Variation of horizon and profile characteristics appears to largely be a function of particle size variability and stratification than topographic position in the catena. The influence of hillslope position on soil redistribution during formation of the Sangamon Geosol appears negligible given the uniformity of upper solum horizon thickness and sandy particle size characteristics, so we conclude that a bioturbation and rainwash origin of the upper solum and the texture contrast in these profiles is not the best process model explanation. We suggest that the base-rich nature of these soils led to ecosystem characteristics that discouraged erosion and encouraged infiltration and a lessivage-type origin of the texture contrast. No convincing evidence of MIS 6 through MIS 4 loess occurs at this site. The Farmdale Geosol formed in the Robein Silt, which is Roxana Silt (MIS 3 loess) that was redistributed downslope. The Robein Silt is thicker and finer in the topographic low and indicates the cooler and forested environmental conditions during MIS 3 were conducive to downslope movement of soil and also produced greater differences in drainage-induced soil morphological changes in the Farmdale Geosol. [Copyright &y& Elsevier]

Experimental pitot pressure measurements in impulse facilities have typically had large-scale harmonic fluctuations associated with them. A combined experimental and numerical approach is used to investigate if a Helmholtz resonance is created from the shrouding that protects the pressure sensor from particle impact, rather than from disturbances being present in the freestream. To verify this experimentally, hydraulic oil was used to change the sound speed in the cavity. Numerical calculations of the pitot probe were used to show that both the steady and the expected transient inflow cause a Helmholtz resonance of similar period. However, a 5 % isothermal level of freestream noise was required to match the experimental fluctuation levels. Viscous effects were also shown to be significant during the initial transient response of the pressure measurement. A new pitot probe design was successfully tested and shown to be able to reduce the magnitude and period of the fluctuations. [ABSTRACT FROM AUTHOR]

The article discusses the Japanese garden designed by Ken Nakajima for the Montreal Botanical Garden in Montreal, Canada. Nakajima was given the title of "National Living Treasure" in Japan and is noted for his modern interpretations of classic Japanese garden styles, especially those of the Edo and aristocratic periods. The author explores how the design expectations of client Pierre Bourque, Director of the Montreal Botanical Garden, caused tension as a result of Nakajima's artistic vision for the garden; considers the public's reaction to the garden; and focuses on the development of and changes made to the garden since its opening in 1988.

Abstract: Huntington''s disease (HD) is a progressive neurological disorder characterised by motor impairments caused by degeneration in the striatum. The mechanism by which the HD mutation leads to the neurodegenerative pathology of HD is still unknown. Recently it was shown that, in HD patients, early pathological changes in white matter precede selective cell death in the striatum. We wondered whether axonal pathology is also an early pathological feature in a transgenic mouse model carrying the HD mutation (R/2 line). R6/2 mice show brain atrophy, a progressive neurological deterioration and skeletal muscle atrophy that resemble those seen in HD patients. However, there is very little neuronal cell loss seen in these animals, even when they show severe symptoms. Here we used sciatic nerve to look for evidence of early neurodegenerative changes in axons of the R6/2 mouse at an ultrastructural level. We observed ultrastructural changes that preferentially affected large myelinated fibres of the sciatic nerve in 10-week-old asymptomatic R6/2 mice. The changes included a significant decrease in the axoplasm diameter of myelinated neurons and an increase in the number of degenerating myelinated fibres compared to age-matched wild type littermates. Myelin thickness and unmyelinated fibre diameter were not affected. The abnormalities described here precede the appearance of overt motor symptoms in the R6/2 mouse and occur in parallel with pathophysiological changes at the neuromuscular junction. We suggest that degenerative changes in axons are likely to contribute to the early pathological phenotype in HD, even in the absence of frank neuronal cell loss. [Copyright &y& Elsevier]

Primary amyloidosis is a plasma cell dyscrasia characterised by excess production of abnormal immunoglobulin light chains with their subsequent accumulation in kidneys, heart, liver as well as gastrointestinal tract and bone marrow 1-21, 2. These tissue deposits take the form of a fibrillar protein which damages the involved organ in proportion to the extent of the infiltration and roughly parallels the duration of the disease. Most cases have evidence of the underlying lymphoplasmacytoid neoplasm recognisable in two ways. Firstly, the monoclone appears in the serum [2]. Secondly is a morphologically and immunohistochemically distinctive cellular infiltrate in the bone marrow [3] that has a specific microscopic and ultrastructural pattern 4-54, 5. Interestingly occasional patients, who survive long enough, may progress to multiple myeloma [6] but the correlation is variable [7]. [ABSTRACT FROM AUTHOR]

Once menorrhagia has been excluded in females then, in both sexes, the gastrointestinal tract remains the commonest site for haemorrhage. This may be of surprisingly large volume but intermittent and therefore not universally demonstrated on stool testing. However, if loss is persistent it may nevertheless culminate in absolute iron deficiency and thus, even when occult blood is not present on repeated examinations, quantitation using chromium labelled red cells becomes invaluable. In this situation, endoscopy or contrast radiology of the small and large bowel may fail to reveal any lesion even when these procedures are repeated or used in combination. Modifications by direct inspection or camera study may be helpful in improving diagnostic accuracy. It is nevertheless practical, as illustrated by these two cases, to more widely recognise the value of radionuclide scanning methods. In one this was due to unsuspected haemobilia and the second to major duodenal vascular malformation although it could be reasonably argued that initial recourse to angiography might have demonstrated this. The principle is that when precisely defined anatomically surgery can be elective and limited as a result of careful proactive planning and operations likely to have a high initial rate of success. The role of nuclear medicine in the investigative algorithm of such patient is re-emphasised. Thus, in any individual with unexplained but proven absolute iron deficiency failure to reveal the cause by first screening with gastroscopy and colonoscopy or barium studies including the small bowel should not automatically be repeated. Rather, the blood loss needs to be documented and, if possible, subsequent evaluation moved to advancement or push enteroscopy, capsule endoscopy or the more invasive angiography only once quantity a pattern of bleeding are defined by radioisoptic imaging. [ABSTRACT FROM AUTHOR]

Cytosine arabinoside and anthracycline-containing regimens induce remission in upwards of 60% of previously untreated patients with adult acute myeloid leukaemia (AML). Despite this, in addition to primary drug resistance, the majority of these patients relapse. Reliable methods for uniformly recognising these two subgroups at presentation do not exist and therefore a further attempt has been made to relate in vitro toxicity, using a clonogenic assay, to clinical outcome. In 10 normal controls and 12 chemotherapy naïve cases, mononuclear cells harvested by density gradient separation were re-suspended at a concentration of 2×10 5 /ml and quadruplicates of 250&ThickSpace;μl per well cultured in methycellulose containing foetal calf serum and phytohaemagglutinin stimulated leucocyte conditioned medium. Cell kill was determined for cytosine arabinoside, daunorubicin and etoposide either singly or in combination using both a pulsed and continuous exposure. Aggregates were scored after seven days and three distinct patterns recognised. The patients all received the same drugs in a standard protocol and achievement of complete remission correlated with growth pattern. The survival of normal marrow colony-forming cells or GM-CFUc and the leukemic equivalent designated L-CFUc were assessed and a sensitivity index (SI) determined as a ratio of these two values in which more reproducible results were found when the drug was continuously present. It is concluded that the microculture technique is feasible and clearly demonstrates chemotherapy effect but no correlation was demonstrated with clinical outcome. This is a negative pilot study and, as a means of recognising drug sensitivity or resistance, should be discarded in favour of currently available molecular techniques. [ABSTRACT FROM AUTHOR]

Abstract: We review the physics of nuclear matter at high energy density and the experimental search for the quark–gluon plasma at the Relativistic Heavy Ion Collider (RHIC). The data obtained in the first three years of the RHIC physics program provide several lines of evidence that a novel state of matter has been created in the most violent, head-on collisions of Au nuclei at GeV. Jet quenching and global measurements show that the initial energy density of the strongly interacting medium generated in the collision is about two orders of magnitude larger than that of cold nuclear matter, well above the critical density for the deconfinement phase transition predicted by lattice QCD. The observed collective flow patterns imply that the system thermalizes early in its evolution, with the dynamics of its expansion consistent with ideal hydrodynamic flow based on a quark–gluon plasma equation of state. [Copyright &y& Elsevier]

Abstract: The amount and vertical distribution of soil organic carbon (SOC) storage is primarily a function of vegetation type and climate, with influence from soil and landscape properties and human activities. The influence of dust aggradation on landscapes during the Holocene has largely been ignored as a factor in long-term SOC storage. Dust aggradation is important to soil horizonation and C sequestration since the dust deposit buries the landscape and increases solum thickness. Mollisols on loess-covered upland tables in central Nebraska have aggraded throughout the Holocene as Bignell Loess accumulated above the late Pleistocene Brady Soil. In the loess tablelands, the thickness of mollic colors, A horizon properties, and SOC storage all decrease with distance from the source of Bignell Loess, which is along a gradient of increasing precipitation. For example, along a 140-km transect of decreasing Bignell Loess thickness and increasing rainfall, total thickness of A horizons decreases by 70 cm and the thickness of mollic colors decreases by 93 cm. Total SOC storage decreases from 17.5 to 7.7 kg/m2. A portion of the SOC in subsurface horizons of modern soils was likely inherited from the Brady Soil, which probably formed in a climate different than the present, suggesting that SOC storage is probably not in equilibrium with modern climatic conditions. Dust aggradation on a biologically active surface in a steppe environment has affected horizonation, pigmentation and SOC storage in central Great Plains loess-derived Mollisols. [Copyright &y& Elsevier]

Evaluates the effectiveness of clarithromycin as treatment for immune agranulocytosis. Case report on a 60-year-old man who experienced recurrent pyrexial illnesses that had no apparent precipitation and recovery for ten years; Description of clarithromycin as a macrolide antibiotic; Epidemiological studies.

This article explores the principles and growth of Japanese garden tradition in different cultures of the world. The garden is a fragile ecosystem of man's manufacture intended to express humans' most cherished ideas of nature. It is subject to the changing forces of nature as much as to the fortunes of man. Its survival over time is never assured and thus a garden tradition is highly problematic in the absence of continuing and creative design, excellence in its execution and an uncompromising commitment to its maintenance and care.

Loess grain size data used to infer transport direction or wind strength are generally derived from vigorously disaggregated samples. However, these data may not adequately represent the effective particle size distribution during loess transport, if the transported dust contained aggregates of fine-grained material. Thin sections of minimally altered C and BC horizons in the late Pleistocene Peoria Loess of Nebraska, USA, indicate the presence of aggregates with diameters of 30–1000 μm. The larger aggregates (>250 μm) are unlikely to have been transported, and are interpreted as the result of soil faunal activity and other pedogenic processes after deposition. Aggregates smaller than 250 μm could have a similar origin, but laser diffraction particle size analysis suggests that many are sedimentary particles. Comparison of minimally and fully dispersed particle size distributions from each sampling site was used to estimate the modal diameter of aggregates. The aggregate modal diameter becomes finer with decreasing loess thickness, representing increasing distance from the source. A similar trend was observed in the modal diameter of fully dispersed particle size distributions, which represents the mode of sand and silt transported as individual grains. We interpret both trends as the result of sorting during transport, supporting the interpretation that many of the aggregates were transported rather than formed in place. Aggregate content appears to increase with distance from the source, explaining a much more rapid downwind increase in clay content than would be expected if clay were transported as particles smaller than 2 μm diameter. Although the Peoria Loess of Nebraska contains sedimentary aggregates, many of the coarse silt and sand grains in this loess were transported as primary particles, were thoroughly exposed to sunlight and are potentially well suited for luminescence dating. [Copyright &y& Elsevier]

This paper reexamines the stratigraphy, sources, and paleoclimatic significance of Holocene Bignell Loess in the central Great Plains. A broadly similar sequence of loess depositional units and paleosols was observed in thick Bignell Loess sections up to 300 km apart, suggesting that these sections record major regional changes in the balance between dust deposition and pedogenesis. New optical ages, together with previously reported radiocarbon ages, indicate Bignell Loess deposition began 9000–11,000 yr ago and continued into the late Holocene; some Bignell Loess is <1000 yr old. There is little evidence that Holocene Loess was derived from flood plain sources, as previously proposed. Instead, thick Bignell Loess occurs mainly near the downwind margins of inactive dune fields, particularly atop escarpments facing the dunes. Thus, the immediate loess source was dust produced when the dunes were active. Previous work indicates that widespread episodes of dune activity are likely to have resulted from drier-than-present climatic conditions. The regionally coherent stratigraphy of Bignell Loess can be interpreted as a near-continuous record of climatically driven variation in dune field activity throughout the Holocene. [Copyright &y& Elsevier]

To state the obvious, Charles Baudelaire was both an inspired artist and a perceptive critic. His poetry and observations of nineteenth-century contemporary art helped formulate the basis of a new French aesthetic, an aesthetic based on the celebration of the commonplace. It was Baudelaire who drew attention to the reflected light from the water in the gutters of the streets of Paris, France, and in so doing, opened the eyes to the latent beauty of everyday, mundane surroundings. It was he who drew attention to the societies of the cabaret as much as those of the literary and artistic salon.

Background : Invasive rhinocerebral mucormycosis is a rare and often fatal opportunistic fungal infection. It is encountered in immunocompromised hosts exemplified by those with diabetes, human immunodeficiency viruses and particularly haematologic malignancies typically after high-dose chemotherapy and stem cell transplantation. In contrast to the more usual outcome with rapid progression and death. We now describe a successful eradication attributable to the use of a newly available antifungal agent. Setting : Haematology department and bone marrow transplantation unit. Material and method : Two patients are contrasted. The first with acute leukaemia developed rapidly progressive facial swelling with mucormycosis proven on biopsy. Treatment over 2 months with maximally tolerated doses of amphotericin failed to halt intracranial extension and death resulted. The second, presented with acute lymphoblastic leukaemia in August 1997, underwent successful autologous bone marrow transplantation in February 1998. Relapse followed in March 1999 and after reinduction and consolidation receive a matched unrelated volunteer allograft in September 1999. A second recurrence was documented in April 2000 and in spite of achieving remission he developed a fever that was managed empirically with intravenous amphotericin and, on discharge, oral itraconazole. Left-sided facial swelling expanded rapidly and biopsy showed extensive invasion of the maxillary sinus with mucormycosis. FK463 was added on 5 June 2000 with gradual reduction in facial pain and within 1 month all clinical signs and resolved. Serial biopsies that included histopathologic investigation and microbiologic cultures confirmed eradication of the invasive mucor. In view of the potential danger of recrudescence this treatment regimen was continued through further chemotherapy and, once again disease-free, a second matched unrelated volunteer allograft took place in August 2000. Full reassessment at the time failed to demonstration any residual fungus. Engraftment was confirmed but neutropenic sepsis resulted in severe inflammatory response syndrome with progression to multiple organ dysfunction to which he succumbed without any evidence of leukaemic or systemic mycosis. Conclusion : Echinocandin FK463 is of documented value in managing invasive candidiasis and aspergillosis. This is believed to be the first case of successful outcome with one of the angiotrophic zygomycetes. [ABSTRACT FROM AUTHOR]

Presents equations for predicting soil organic carbon using loss-on-ignition for North Central U.S. soils. Differences between predictive equations for individual major land resource areas; Recommendation to develop predictive equations for individual soil-geographic regions.

The myelodysplastic syndromes are increasingly recognised clinical entities reflecting a stem cell defect that gives rise to ineffective clonal haematopoiesis. The spectrum extends from relatively indolent refractory anaemia through varying combinations of leucopoenia and thrombocytopenia to acute leukaemia. Diagnosis rests on marrow hypercellularity with dysplastic morphology, apoptosis and, often distinctive cytogenetic defects. Stratification to risk-related protocols range from occasional blood transfusions or erythropoietin through innovative options including thalidomide or amifostine to haematopoietic stem cell transplantation in selected individuals. Acute myeloid leukaemia, conceptually segregated from preleukaemia, is treated differently although accumulating cellular and molecular data favour a more integrated approach. Morphology and immunopheno-typing are complemented by molecular genetics. On this basis chemotherapy alone is sufficient in defined sub- groups whereas others benefit by autologous or allogeneic grafting. Attention to demonstrating minimal residual disease is the basis for more specific intervention exemplified by monoclonal antibodies or maturation-inducing agents as with retinoic acid in acute progranulocytic leukaemia [ABSTRACT FROM AUTHOR]