Heterogeneous melting near the Thwaites Glacier grounding line.

Thwaites Glacier represents 15% of the ice discharge from the West Antarctic Ice Sheet and influences a wider catchment1-3. Because it is grounded below sea level4,5, Thwaites Glacier is thought to be susceptible to runaway retreat triggered at the grounding line (GL) at which the glacier reaches the ocean6,7. Recent ice-flow acceleration2,8 and retreat of the ice front8-10 and GL11,12 indicate that ice loss will continue. The relative impacts of mechanisms underlying recent retreat are however uncertain. Here we show sustained GL retreat from at least 2011 to 2020 and resolve mechanisms of ice-shelf melt at the submetre scale. Our conclusions are based on observations of the Thwaites Eastern Ice Shelf (TEIS) from an underwater vehicle, extending from the GL to 3 km oceanward and from the ice-ocean interface to the sea floor. These observations show a rough ice base above a sea floor sloping upward towards the GL and an ocean cavity in which the warmest water exceeds 2 °C above freezing. Data closest to the ice base show that enhanced melting occurs along sloped surfaces that initiate near the GL and evolve into steep-sided terraces. This pronounced melting along steep ice faces, including in crevasses, produces stratification that suppresses melt along flat interfaces. These data imply that slope-dependent melting sculpts the ice base and acts as an important response to ocean warming.

The role of transcranial magnetic stimulation in understanding attention-related networks in single subjects.

Attention is a cognitive mechanism that has been studied through several methodological viewpoints, including animal models, MRI in stroke patients, and fMRI in healthy subjects. Activation-based fMRI research has also pointed to specific networks that activate during attention tasks. Most recently, network neuroscience has been used to study the functional connectivity of large-scale networks for attention to reveal how strongly correlated networks are to each other when engaged in specific behaviors. While neuroimaging has revealed important information about the neural correlates of attention, it is crucial to better understand how these processes are organized and executed in the brain in single subjects to guide theories and treatments for attention. Noninvasive brain stimulation is an effective tool to causally manipulate neural activity to detect the causal roles of circuits in behavior. We describe how combining transcranial magnetic stimulation (TMS) with modern precision network analysis in single-subject neuroimaging could test the roles of regions, circuits, and networks in regulating attention as a pathway to improve treatment effect magnitudes and specificity.

Wheat germ supplement reduces cyst and trophozoite passage in people with giardiasis.

The protozoan parasite Giardia lamblia is a major cause of waterborne enteric disease worldwide. Lectins are proteins that bind to carbohydrate (sugar) moieties. Potential targets for lectins are found on the surface of most single-celled organisms. Modest concentrations of wheat germ agglutinin (WGA) have been shown to inhibit G. lamblia excystation and trophozoite growth in vitro and can reduce cyst passage in mice infected with the closely related protozoan parasite, G. muris. Commercial preparations of wheat germ (WG) contain 13-53 microg of WGA per gram. We performed a double-masked, placebo-controlled study of dietary supplementation with WG in 63 subjects with giardiasis in Montreal and Lima (25 asymptomatic patients passing cysts; 38 patients with symptoms). Asymptomatic subjects received WG (2 g, 3 times a day) or placebo (cornstarch, 2 g, 3 times a day) for 10 days, followed by metronidazole (250 mg 3 times a day) for 7 days. Symptomatic subjects received metronidazole (250 mg 3 times a day) plus either WG or placebo for 7 days. Stool specimens were collected every day (Montreal) or every other day (Lima) for 10 days and on Day 35 for microscopic examination and coproantigen determination. Subjects kept a diary of symptoms for 10 days after recruitment. In asymptomatic subjects, both cyst passage and coproantigen levels were reduced by approximately 50% in those taking WG compared with the placebo group (P < 0.01 and P = 0.06, respectively). In symptomatic subjects, cyst passage and coproantigen levels fell precipitously in response to metronidazole therapy, and there were no clinically important differences between those receiving supplemental WG or placebo. However, symptoms appear to have resolved more rapidly in the subjects taking WG in addition to metronidazole. The WG supplement was well tolerated in both symptomatic and asymptomatic subjects. These data suggest that components of WG, possibly WGA, either alone or in combination with antiprotozoal agents, can influence the course of human giardiasis.

A randomized, crossover comparison of warfarin products in the treatment of chronic atrial fibrillation.

OBJECTIVE: To compare the dosing requirements and international normalized ratios (INRs) associated with two bioequivalent crystalline warfarin sodium products in patients with chronic atrial fibrillation. METHODS: A multicenter, single-blind (prescriber), randomized, crossover evaluation of Apothecon warfarin and DuPont warfarin (Coumadin) was conducted in consenting adults with chronic or paroxysmal atrial fibrillation who had been receiving DuPont warfarin chronically for the prevention of thromboembolism. Patients were randomly assigned to initially either continue DuPont warfarin or receive Apothecon warfarin for four weeks, with weekly evaluation of dosage and INR changes, safety, and efficacy. Subsequently, patients crossed over and received the other product for four weeks. RESULTS: There were 113 patients randomized to receive study treatment. Neither the propensity for a dosage change or an INR change nor the magnitude of a dosage change or INR change appeared related to a particular warfarin product (NS for each variable after each study period). After four weeks of treatment, the same number of patients (n = 7) experienced a > or = 20% change in warfarin dosage from the respective baseline with each product. The number of patients with INRs outside the desired protocol range after four weeks of treatment was similar for both groups (< 1.8, n = 9 for both products, or > 3.2, n = 9 for DuPont, n = 10 for Apothecon). No major hemorrhagic or thromboemoblic events occurred. CONCLUSIONS: The results of this study show that Apothecon warfarin and DuPont warfarin provide equivalent anticoagulation in patients with chronic or paroxysmal atrial fibrillation.

Update on vitamin supplements for the prevention of coronary disease and stroke.

Dietary antioxidants and folic acid may play a role in the pathophysiology of coronary disease and stroke. We review patient-oriented evidence on the effectiveness of supplementation with antioxidants and/or folic acid in the prevention of myocardial infarction and stroke. Observational data suggest cardiovascular benefit of vitamin E supplementation, but results of controlled clinical trials are inconsistent regarding the effect on nonfatal myocardial infarction. Moreover, studies have not shown a protective effect of vitamin E against fatal myocardial infarction and have not addressed stroke. For vitamin C and folic acid supplementation, observational data are inconsistent and controlled clinical trials are lacking. Thus, the available evidence is insufficient to recommend the routine use of vitamin E, vitamin C or folate supplements for the prevention of myocardial infarction or stroke. The evidence argues against the use of beta carotene supplements for this purpose. The costs and risks associated with these supplements are low, however, and physicians may choose to recommend vitamin E, folate and/or vitamin C supplementation pending conclusive evidence from clinical trials.

Update on oral contraceptive pills.

Oral contraceptive pills are widely used and are generally safe and effective for many women. The World Health Organization has developed a risk classification system to help physicians advise patients about the safety of oral contraceptive pills. The choice of pill formulation is influenced by clinical considerations. By choosing appropriately from the available pill formulations, family physicians can minimize negative side effects and maximize noncontraceptive benefits for their patients. Additional monitoring and follow-up are necessary in special populations, such as women over 35 years of age, smokers, perimenopausal women and adolescents. Third-generation progestins are additional options for achieving noncontraceptive benefits, but their use has raised new questions about thrombogenesis. The U.S. Food and Drug Administration has labeled emergency postcoital contraception for use following unprotected coitus. Oral contraceptive pills are associated with few clinically significant drug interactions, although consideration of interactions remains important.

Defecation practices of young children in a Peruvian shanty town.

Little is known about feces disposal practices, their determinants and feasibility for change, despite their importance in the control of diarrheal diseases. We report here the results of formative research for the development of an intervention to promote sanitary disposal of feces of young children. The study was conducted in a densely populated shanty town area of Lima, where water and sanitation systems are scarce. In-depth interviews were undertaken with mothers, husbands and community leaders. Group discussions were held with mothers in order to validate findings from the interviews, investigate particular topics further and explore reactions to possible intervention strategies. The principal defecation sites for young children were diapers, potties, the ground in or near the home, the hill, latrines and flush toilets. The main determinants found were the age of the child, the effort required by the method, perceptions of dirtiness and the availability of resources. Almost all children under one year of age use diapers but the high resource cost of diaper washing is a strong motivation for mothers to move their children on as early as possible. Potties were considered the most socially acceptable and 'hygienic' defecation method for children between one and three years of age. Nevertheless, defecation directly onto the ground is common at this age. Potty training is deemed to be quite difficult and the long term achievements are determined by the initial training success. In most cases, the training process is authoritative and inconsistent. The use of latrines and flush toilets is not considered appropriate for children until they are three to four years old. Based on these initial findings, a micro-trial was conducted to assess the feasibility and acceptability of promoting greater use of potties and associated practices. The results of the trial were very encouraging and provided valuable information for the design of a community-wide intervention. Our findings help explain why the emphasis given in most sanitation projects, where efforts have been concentrated on the promotion of latrines, has failed to induce their utilization by small children. Sanitation projects should incorporate interventions that will promote hygienic defecation and stool clearance practices for infants and small children.

Treatment of type 2 diabetes mellitus.

Type 2 diabetes mellitus (formerly called non-insulin-dependent diabetes) causes abnormal carbohydrate, lipid and protein metabolism associated with insulin resistance and impaired insulin secretion. Insulin resistance is a major contributor to progression of the disease and to complications of diabetes. Type 2 diabetes is a common and underdiagnosed condition that poses treatment challenges to family practitioners. The introduction of new oral agents within the past three years has expanded the range of possible combination regimens available for treating type 2 diabetes. Despite the choice of pharmacologic agents, physicians must stress the nonpharmacologic approaches of diet modification, weight control and regular exercise. Pharmacologic approaches must be based on patient characteristics, level of glucose control and cost considerations. Combinations of different oral agents may be useful for controlling hyperglycemia before insulin therapy becomes necessary. A stepped-care approach to drug therapy may provide the most rational, cost-efficient approach to management of this disease. Pharmaco-economic analyses of clinical trials are needed to determine cost-effective treatment strategies for management of type 2 diabetes.

Low-molecular-weight heparin in outpatient treatment of DVT.

Patients with a diagnosis of acute deep venous thrombosis have traditionally been hospitalized and treated with unfractionated heparin followed by oral anticoagulation therapy. Several clinical trials have shown that low-molecular-weight heparin is at least as safe and effective as unfractionated heparin in the treatment of uncomplicated deep venous thrombosis. The use of low-molecular-weight heparin in an outpatient program for the management of deep venous thrombosis provides a treatment alternative to hospitalization in selected patients. Use of low-molecular-weight heparin on an outpatient basis requires coordination of care, laboratory monitoring, and patient education and participation in treatment. Overlapping the initiation of warfarin permits long-term anticoagulation. Advantages include a decreased incidence of heparin-induced thrombocytopenia and fewer episodes of bleeding complications. Future clinical trials evaluating the safety and efficacy of low-molecular-weight heparin in the treatment of complicated deep venous thrombosis will further define appropriate indications for use and strategies for outpatient management.

Feces, flies, and fetor: findings from a Peruvian shantytown.

Sanitary disposal of feces is vital to combat childhood diarrhea, and its promotion is key to improving health in developing countries. Knowledge of prevailing feces disposal practices is a prerequisite to formulation of effective intervention strategies. Two studies were conducted in a shantytown area of Lima, Peru. First, information was gathered through in-depth interviews with mothers and structured observations (4 hours) of young children and their caretakers. Data on beliefs and practices related to feces disposal behaviors were obtained. Excreta were deposited by animals or humans in or near the house in 82% of households observed. Beliefs about feces depended on their source and were reflected in how likely the feces were to be cleared. While 22% of children aged > or = 18 months were observed to use a potty for defecation, 48% defecated on the ground where the stools often remained. Although almost all children were cleaned after defecation, 30% retained some fecal matter on their body or clothes. Handwashing after the child's defecation was extremely rare for both children (5%) and caretakers (20%). The hygienic disposal of feces poses problems in this type of community. Nevertheless existing practices were found that show promise for promotion on a wider scale, including greater use of potties.

What is the role of angiotensin-converting enzyme inhibitors in congestive heart failure and after myocardial infarction?

OBJECTIVE: To discuss the controversies surrounding the choice of angiotensin-converting enzyme (ACE) inhibitor, and the timing, dosage, and duration of ACE inhibitor therapy for congestive heart failure (CHF) and after myocardial infarction (MI). The beneficial effects of ACE inhibition in patients with CHF and after MI are reviewed. Human clinical trials are reviewed and their clinical implications are discussed. DATA SOURCES: MEDLINE searches (1985-1995) identified human clinical trials and review articles. DATA EXTRACTION: Landmark human clinical trials with morbidity and mortality end points were included. The validity of the study data were assessed on the basis of study methods, population characteristics, and statistical power. DATA SYNTHESIS: ACE inhibitors exert beneficial effects in patients with CHF by hemodynamic and neurohormonal mechanisms. The attenuation of ventricular remodeling that occurs with ACE inhibition does not fully explain the results of clinical trials in patients after MI. Routine determination of ejection fraction to guide ACE inhibitor therapy is not as important as the patient's clinical status. Clinicians should titrate the chosen ACE inhibitor on the basis of hemodynamic response to target doses used in major clinical trials. Because the beneficial effects of ACE inhibitors appear to be a class effect, choice of an agent should include cost considerations and the results of clinical trials. CONCLUSIONS: ACE inhibitor reduce morbidity and mortality in selected CHF and post-MI patients. Patients with symptomatic CHF benefit most from ACE inhibitor therapy, and it should be continued indefinitely. Treatment effects in asymptomatic patients are delayed. The role of ACE inhibitor therapy in preventing morbidity and morality in asymptomatic patients with preserved ventricular function requires further study.

Management of the behavioral manifestations of dementia.

Dementia affects 5% of persons over age 65 years and 20% of those over 80 years of age and is expected to increase further in the primary care setting as the population ages. The constellation of neuropsychiatric disorders includes dementia, organic personality disorder, and organic psychotic disorder. Dementia is the most prevalent disorder, accounting for approximately 70% of the neuropsychiatric disease of institutionalized patients.

Transmission factors and socioeconomic status as determinants of diarrhoeal incidence in Lima, Peru.

As part of a longitudinal, community-based study of diarrhoeal morbidity in a peri-urban community in Lima, Peru, a household survey was administered to ascertain possible risk factors, based on transmission routes, for diarrhoeal incidence. Socioeconomic information was also obtained in the survey and a composite socioeconomic status (SES) indicator was created based on four variables: income (wealth), ownership of 4 functioning electrical household appliances, community participation, and house construction. Both transmission factors and the SES indicator were analysed for their effects on diarrhoeal incidence using both bivariate and multivariate methods. The SES indicator, method of water storage, if the child was seen eating faeces or soil were all significantly associated with diarrhoeal incidence. In a final logistic model, water storage, location of defecation for children, child eating soil or faeces, and age, demonstrated significant results. Children in households with water stored in containers without a faucet were twice as likely to have a high incidence of diarrhoea (greater than 7 episodes/child/year). The SES indicator was not significant in the logistic model, but high SES was associated with whether or not the child was reported as having been seen eating faeces or soil and with non-use of latrines by adults. Also low SES households were more likely to have better water storage methods. Therefore, it would seem that (SES) does not independently determine diarrhoeal incidence, but rather may be functioning through these transmission factors to affect diarrhoeal incidence.

The impact of sonography on the management of extratesticular abnormalities of the scrotum.

The results of scrotal sonography performed in a recent one-year period (1987) were retrospectively reviewed to assess the role of sonography in the management of patients with extratesticular abnormalities. The study included 226 examinations performed in 204 men. In extratesticular abnormalities, scrotal sonography confirms the clinical impression of the referring physicians, monitors the progress of conservative treatment, and guides the surgical approach. Patients with sonographically classic cystic extratesticular abnormalities rarely come to surgery. Those with complicated cystic abnormalities are usually followed clinically but have a higher incidence of surgery. Those with solid-appearing echogenic abnormalities usually have surgical removal.