Mars Extant Life: What's Next? Conference Report.

On November 5-8, 2019, the "Mars Extant Life: What's Next?" conference was convened in Carlsbad, New Mexico. The conference gathered a community of actively publishing experts in disciplines related to habitability and astrobiology. Primary conclusions are as follows: A significant subset of conference attendees concluded that there is a realistic possibility that Mars hosts indigenous microbial life. A powerful theme that permeated the conference is that the key to the search for martian extant life lies in identifying and exploring refugia ("oases"), where conditions are either permanently or episodically significantly more hospitable than average. Based on our existing knowledge of Mars, conference participants highlighted four potential martian refugium (not listed in priority order): Caves, Deep Subsurface, Ices, and Salts. The conference group did not attempt to reach a consensus prioritization of these candidate environments, but instead felt that a defensible prioritization would require a future competitive process. Within the context of these candidate environments, we identified a variety of geological search strategies that could narrow the search space. Additionally, we summarized a number of measurement techniques that could be used to detect evidence of extant life (if present). Again, it was not within the scope of the conference to prioritize these measurement techniques-that is best left for the competitive process. We specifically note that the number and sensitivity of detection methods that could be implemented if samples were returned to Earth greatly exceed the methodologies that could be used at Mars. Finally, important lessons to guide extant life search processes can be derived both from experiments carried out in terrestrial laboratories and analog field sites and from theoretical modeling.

Acute effect of high-calcium milk with or without additional magnesium, or calcium phosphate on parathyroid hormone and biochemical markers of bone resorption.

OBJECTIVE: To assess whether there are any differences in the postprandial physiological responses to apple drink (control), calcium phosphate (tricalcium phosphate, TCP) and high-calcium skim milk (HCSM) with or without additional magnesium in postmenopausal women. DESIGN: Randomized, controlled, cross-over. Measurements after overnight fast before each drink, and subsequently every hour for 8 h postprandially. SETTING: Human Nutrition Studies Laboratory, Milk and Health Research Centre, Massey University, Palmerston North, New Zealand. SUBJECTS: Twenty-one healthy postmenopausal women. INTERVENTION: Four drinks, each 400 ml. (1) Apple drink (25% fruit juice). (2) TCP dispersed in water containing 1200 mg Ca. (3) HCSM containing 1200 mg Ca and 65.5 mg Mg. (4) HCSM containing 1200 mg Ca and 172 mg Mg. RESULTS: There was no difference in baseline serum calcium, PTH or C-telopeptide levels between drinks. There were no overall differences in serum calcium after apple or after either milk, but after TCP serum calcium increased from a baseline value of 2.12+/-0.08 to a mean peak of 2.21+/-0.12 mmol/l (s.d.) (P=0.0001) after 2 h. There were no significant differences in serum PTH after either apple or HCSM+Mg. In contrast, after TCP, serum PTH decreased from 2.76+/-0.69 to a mean nadir of 2.23+/-0.65 pmol/l (P=0.0001) after 1 h, and after HCSM, it decreased from 2.71+/-0.78 to a mean nadir of 2.51+/-0.87 pmol/l (P=0.007) after 2 h. Serum C-telopeptides decreased after each drink, reaching nadirs after 5 h. At this time the serum values for each of the high calcium drinks were not different from each other, but were significantly less than for apple (P=0.001 for each), being 0.22+/-0.09 ng/ml for apple, 0.15+/-0.08 for TCP, 0.14+/-0.07 for HCSM and 0.16+/-0.07 for HCSM+Mg. CONCLUSION: Despite differences in serum calcium and PTH responses to the three high-calcium drinks that we tested, there was no distinguishable difference in serum C-telopeptides between high calcium drinks.

Lack of awareness of public health promotion messages among a group of adult New Zealanders who meet national guidelines for food intake and physical activity.

The aim of this study was to assess the awareness of national health promotion messages in a group of self-selected New Zealanders. This study involved 104 self-selected New Zealanders (41 men and 63 women) over the age of 40. Awareness of national health promotion messages was assessed using a mailed out questionnaire, and 69 of these were returned. Basic anthropometric measurements were made (height, weight, hip and waist circumference) and habitual physical activity was defined using a questionnaire. Food intake was estimated by 24-h dietary recall. Overall, this group of people met the New Zealand national guidelines for exercise, physical activity and food intake. There was good awareness of the public health organisations in New Zealand, but only half the people that we sampled had a general idea about the content of the health messages of these organisations. This group of New Zealand adults had a healthy lifestyle that was not associated with a high awareness of public health messages, suggesting that other sources of health information are used.

Correlations between biochemical markers of bone resorption and creatinine excretion.

There were two reasons for doing this study. The first was to assess whether expressing biochemical markers of bone resorption as a ratio to creatinine excretion influences the correlations between them. The second was to assess whether biochemical markers of bone resorption are correlated with creatinine excretion, which is a biomarker of muscle mass. Three biochemical markers of bone resorption, free deoxypyridinoline (DPD), N-telopeptides (NTx) and C-telopeptides (CTx), together with creatinine (cr), were measured in 24-h urine samples of 45 healthy people (26 women and 19 men). The urinary concentrations of DPD, NTx and CTx were highly correlated with each other. These relationships were weakened, or no longer statistically significant, when the markers were expressed as a ratio to cr excretion. The 24-h excretion of each of the markers was correlated with 24-h cr excretion in men, but only 24-h DPD was correlated with 24-h cr excretion in the women. The men had significantly higher 24-h excretion rates of each of the markers than the women did. Since muscle mass is related to skeletal mass, these data suggest that in healthy people the rate of bone resorption may be a function of skeletal size as well as the rate of bone turnover. For small human studies 24-h urine sampling is recommended in preference to untimed sampling. However, for clinical purposes, or for large clinical trials, this may not be practical.

The United States National Prospective Hemolytic Uremic Syndrome Study: microbiologic, serologic, clinical, and epidemiologic findings.

The frequency of Shiga toxin-producing Escherichia coli (STEC) serotypes associated with postdiarrheal hemolytic uremic syndrome (HUS) cases among children and adults in the United States and the proportion with IgM or IgG lipopolysaccharide antibodies to E. coli O157 were determined by use of a nationwide sample from January 1987 through December 1991. Among 83 patients, STEC were isolated from 30 (43%) of 70 whose stool cultures yielded bacterial growth (25 E. coli O157 isolates and 5 non-O157 STEC isolates). Fifty-three (80%) of 66 patients with serum samples had positive O157 lipopolysaccharide antibody titers. Of the 83 patients, 60 (72%) had evidence of STEC infection, including 6 of 8 adults whose illnesses also met criteria for thrombotic thrombocytopenic purpura. Data from a subset of patients suggest that E. coli O157 was the cause of > or = 80% of the STEC infections. All 3 women who were postpartum had evidence of E. coli O157 infection. STEC infection should be considered the likely cause for all persons with postdiarrheal HUS.

Shiga-like toxin-producing Escherichia coli O111 and associated hemolytic-uremic syndrome: a family outbreak.

OBJECTIVE: To describe a family cluster of Shiga toxin-producing Escherichia coli O111ac:NM infection. STUDY DESIGN: The index case was identified as part of a United States prospective study of hemolytic-uremic syndrome. Epidemiologic investigation was conducted through interviews. E. coli O111:NM infection was characterized through culture and serology. Shiga toxin 1 and 2 gene sequences were determined with oligonucleotide DNA probes. RESULTS: All three children and both parents had nonbloody diarrhea, vomiting and abdominal cramps, and one child developed hemolytic-uremic syndrome. Shiga toxin 1- and 2-producing E. coli O111ac:NM was isolated from two children. IgG antibodies to E. coli O111 were detected in all three children. CONCLUSIONS: To our knowledge this is the first reported cluster of O111 infection and only the second caused by non-O157 Shiga toxin-producing E. coli in North America.

Meat grinders and molecular epidemiology: two supermarket outbreaks of Escherichia coli O157:H7 infection.

Between 23 June and 15 July 1994, 21 cases (19 primary and 2 secondary) of Escherichia coli O157:H7 infection were identified in the Bethel, Connecticut, area. Three pulsed-field gel electrophoresis (PFGE) patterns from 15 isolates (I, n = 13; II, n = 2; and III, n = 1) were observed. A case-control study that excluded secondary cases and patients with PFGE II and III patterns (n = 16) demonstrated that consumption of food from one supermarket was associated with illness (15/16 cases vs. 31/47 geographically matched controls, odds ratio [OR] undefined, lower 95% confidence interval OR = 1.45, P = .018). No one food was associated with illness. Inspection of the supermarket revealed deficiencies in hygiene and meat handling practices. The 2 cases with PFGE II ate raw beef and raw lamb from a second supermarket. These outbreaks demonstrate the value of PFGE in supporting epidemiologic investigations and the potential for outbreaks arising from retail outlets.

Detection of amphiregulin and Cripto-1 in mammary tumors from transgenic mice.

Epidermal growth factor family members are widely expressed in human breast cancer and are thought to play an important dual role in mammary gland development and tumorigenesis. Overexpression of two relatively new members of this family, amphiregulin (AR) and Cripto-1 (CR-1), has been previously shown to transform immortalized human and mouse mammary epithelial cells. Here, we extend these results and address the disregulated expression of AR and CR-1 in many types of transgenic neoplastic mouse mammary tissues. Transgenic mouse strains overexpressing the oncogenes transforming growth factor-alpha, neu, int-3, polyoma virus middle T antigen, and simian virus 40 large T antigen have been previously shown to develop spontaneous mammary neoplasia. These models were each examined for mammary-tumor expression of AR and CR-1 by reverse transcription-polymerase chain reaction, western blot, and immunocytochemical analyses. Mammary tumors from each source expressed AR and CR-1. Western blot analysis revealed that, in all mammary tumors, AR and CR-1 protein species were processed differently than in virgin and lactating mouse mammary tissue. In addition, immunohistochemical detection of AR and CR-1 in tumor tissue revealed different patterns of growth-factor localization in different types of transgenic mouse mammary-derived tumors. These findings are consistent with the possibility of widespread roles for AR and CR-1 in the promotion and/or progression stages of mouse mammary tumorigenesis.

Laboratory investigation of a multistate food-borne outbreak of Escherichia coli O157:H7 by using pulsed-field gel electrophoresis and phage typing.

Two hundred thirty-three isolates of Escherichia coli O157:H7 were analyzed by both pulsed-field gel electrophoresis (PFGE) and bacteriophage typing. All 26 isolates from persons whose illness was associated with a recent multistate outbreak of E. coli O157:H7 infections linked to the consumption of undercooked hamburgers and all 27 isolates from incriminated lots of hamburger meat had the same phage type and the same PFGE pattern. Twenty-five of 74 E. coli O157:H7 isolates from Washington State and 10 of 27 isolates from other states obtained during the 6 months before the outbreak had the same phage type as the outbreak strain, but only 1 isolate had the same PFGE pattern. PFGE thus appeared to be a more sensitive method than bacteriophage typing for distinguishing outbreak and non-outbreak-related strains. The PFGE patterns of seven preoutbreak sporadic isolates and five sporadic isolates from the outbreak period differed from that of the outbreak strain by a single band, making it difficult to identify these isolates as outbreak or non-outbreak related. Phage typing and PFGE with additional enzymes were helpful in resolving this problem. While not as sensitive as PFGE, phage typing was helpful in interpreting PFGE data and could have been used as a simple, rapid screen to eliminate the need for performing PFGE on unrelated isolates.

Resting energy expenditure and substrate oxidation rates in cystic fibrosis.

The resting energy expenditure (REE) and substrate oxidation rates in 16 patients with cystic fibrosis who had mild chest disease and 11 healthy controls were measured using indirect calorimetry. The mean REE (% predicted) in the patients with cystic fibrosis was 11% greater than in the controls. Five patients with cystic fibrosis were hypermetabolic but only one of these had a clinically significant reduction of respiratory function. A greater proportion of REE was derived from carbohydrate oxidation in the cystic fibrosis patients (43.5% v 29.9%). However, the 24 hour dietary intake of carbohydrate was greater in the cystic fibrosis group (49.6 v 45.8% of energy intake). These data suggest that a high dietary intake of carbohydrate may contribute to the increased oxidation of carbohydrate in these cystic fibrosis patients. All patients with cystic fibrosis, including those with apparently mild lung disease, should continue to receive a high energy diet.

Weight loss in chronic obstructive pulmonary disease.

Weight loss occurs in about a third or more disabled patients with chronic obstructive pulmonary disease (COPD), and appears to be a poor prognostic factor. As such, it correlates only weakly with FEV1, transfer factor and other measures of respiratory physiology and is probably, to a certain extent, independent of them. Recent studies of basal metabolic rate (BMR) in COPD using steady-state, non-invasive calorimetry, have shown it to be elevated by 10-20% in up to 40% of such patients. It is likely that this represents true hypermetabolism per kilogram of fat free mass. An elevated BMR cannot be predicted from combinations of detailed lung function tests or arterial gases, as patients with similar physiology have differing BMRs. Thus, although an increased work of breathing is the probable explanation for some of the increase, other factors such as cytokines or possibly drug therapy almost certainly contribute. Muscle loss in weight-losing COPD appears to involve both type I and type II fibres, because of a combination of reduced calorie intake and disuse atrophy. Respiratory muscles share this fibre loss. Review of the controlled studies on nutritional supplementation in COPD suggests that an energy increase of about 30% is needed to achieve substantial weight gain and improve exercise tolerance. Fat-rich supplements have some theoretical advantages. Further work is needed particularly with regard to the determinants of the increased BMR in COPD, and the effect of longer term nutritional supplements on prognosis.

Estimation of body composition from bioelectrical impedance of body segments: comparison with dual-energy X-ray absorptiometry.

In twenty-eight healthy subjects, ten men and eighteen women, with a range in body mass index (BMI) of 17.9-31.6 kg/m2 and an age range 20-60 years, body composition was estimated by dual-energy X-ray absorptiometry (DEXA), skinfold anthropometry (SFA) and bioelectrical impedance analysis (BIA) of the 'whole body' and body segments. In thirteen subjects muscle mass was also estimated by 24 h urinary creatinine excretion. The relationship between fat-free mass (FFM) determined by DEXA and the impedance index of each body segment (calculated as length2/impedance (Z)) was analysed. The strongest correlation was between FFM (DEXA) and height2/'whole-body' Z (ZW) (r 0.97 for the combined sexes, standard error of estimate (SEE) 2.72 kg). Separate prediction equations were found to be necessary for males and females when estimating FFM from BIA measurement of the arm (for men, r 0.93, SEE 1.98 kg; for women, r 0.75, SEE 2.87 kg). Muscle mass derived from 24 h creatinine excretion showed weak correlation with FFM (DEXA) (r 0.57, P = 0.03) and no correlation with FFM (SFA). FFM (SFA) correlated well with both FFM (DEXA) (r 0.96, SEE = 3.12 kg) and with height2/ZW (r 0.92, SEE 4.52 kg). Measurement of the impedance of the arm offers a simple method of assessing the composition of the whole body in normal individuals, and it appears comparable with other methods of assessment.

Comparisons between basal metabolic rate and diet-induced thermogenesis in different types of chronic obstructive pulmonary disease.

1. Some patients with the emphysematous type of tobacco-related chronic obstructive pulmonary disease are hypermetabolic. Since the likely mechanism is the increased work of breathing, other groups of patients with chronic obstructive pulmonary disease should be similar. We have now measured basal metabolic rate and diet-induced thermogenesis in six patients with chronic obstructive pulmonary disease with an arterial partial pressure of CO2 of less than 5 kPa (emphysematous), nine patients with chronic obstructive pulmonary disease with an arterial partial pressure of CO2 of greater than 6 kPa (bronchitic), eight patients with chronic obstructive pulmonary disease due to chronic asthma and seven control subjects. Diet-induced thermogenesis was measured for 4h after a meal of 87% carbohydrate, 11% protein and 2% fat as energy, with a total energy content of 40% of basal metabolic rate. 2. There was no difference between measured and predicted basal metabolic rate in the control (5541 +/- 272 versus 5881 +/- 245 kJ/24h) or emphysematous (5552 +/- 370 versus 6239 +/- 197 kJ/24h) groups, but measured basal metabolic rate was significantly higher than predicted in the bronchitic (6126 +/- 387 versus 5405 +/- 250 kJ/24h) and asthmatic (6293 +/- 197 versus 5701 + 245, mean +/- SEM, P less than 0.01) groups. All the control subjects had measured basal metabolic rates within 10% of predicted, whereas two out of six emphysematous patients, four out of nine bronchitic patients and five out of eight asthmatic patients were hypermetabolic. The contributions of fat, carbohydrate and protein oxidation rates to the overall basal metabolic rate were similar between groups. 3. Diet-induced thermogenesis was similar between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Nutritional management of patients with short-bowel syndrome.

The healthy small intestine plays a vital role in the absorption of fluid, electrolytes, and nutrients. This function is severely compromised after surgical resection, although the remaining gut has a large capacity for adaptation. The nature of the nutritional support offered to patients with short-bowel syndrome depends on the length and site of small intestine resected, time after surgery, underlying disease, and nutritional status of the patient. If sufficient gut remains, oral supplementation is the treatment of choice, but attention must be given to potential malabsorption, particularly of micronutrients. Oral feeding is perhaps the most important means of promoting intestinal adaptation, which can be much delayed. Inevitably, some patients will not be able to tolerate or thrive on oral nutrition, and these few may need to resort to intravenous feeding support. This approach is often considerably challenging and should be managed only by those with expertise, because numerous and sometimes significant difficulties can be encountered.

Catabolic effect of dexamethasone in the preterm baby.

Most babies treated with dexamethasone for bronchopulmonary dysplasia exhibit an appreciable rise in the blood urea concentration, from a mean of 2.3 mmol/l before steroid to a mean of 7.1 mmol/l after. In order to discover whether this was primarily the result of increased protein catabolism, nitrogen balance studies before and after the start of dexamethasone were performed and a mean deficit in nitrogen retention of 158 mg/kg/24 hours was found. Similarly the urinary 3-methylhistidine (3MH):creatinine ratio before and after the commencement of dexamethasone treatment in a group of preterm babies was measured. It was found that there was a substantial increase in 3MH excretion after dexamethasone: from a mean 3MH:creatinine ratio of 46 in the week before steroids to a mean ratio of 77 in the week after. As 3MH emanates almost exclusively from the breakdown of actin in skeletal muscle cell, this finding implies the loss of muscle tissue. It was also found that the babies were in less positive nitrogen balance after dexamethasone, to a degree which is significant relative to their protein reserves. The long term consequences of a period of increased catabolism are not yet known but the authors suggest caution in the use of dexamethasone, at least in babies with milder degrees of bronchopulmonary dysplasia in whom the ratio of benefit to risk may be less favourable.

Are patients with primary biliary cirrhosis hypermetabolic? A comparison between patients before and after liver transplantation and controls.

Wasting is common in end-stage primary biliary cirrhosis and causes concern in patients facing liver transplantation. We have quantified resting metabolic rate and diet-induced thermogenesis in seven patients with primary biliary cirrhosis, in seven patients after liver transplantation who had previously been diagnosed as having primary biliary cirrhosis and in seven controls. Resting metabolic rate was elevated in the primary biliary cirrhosis group (4.44 +/- 0.81 kJ/hr/kg body wt; mean +/- S.D.) compared with the post-liver-transplantation group (3.39 +/- 0.40 kJ/hr/kg body wt) (p less than 0.005) and compared with control subjects (3.65 +/- 0.23 kJ/hr/kg body wt) (p less than 0.01). A highly significant relationship was found between the severity of liver disease in the primary biliary cirrhosis group, as assessed by Child-Pugh score, and the resting metabolic rate group (r = 0.93; p less than 0.005). After a liquid meal (41 kJ/kg body wt), the metabolic rate increased, with similar peak changes from baseline occurring in all three groups. However, the rise persisted significantly longer in the primary biliary cirrhosis patients, and thus the integrated mean postprandial energy expenditure over the 4-hr postprandial observation period was greater in the primary biliary cirrhosis group than in the other two groups (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)