Estimating how many undescribed species have gone extinct.

Because both descriptions of species and modern human-driven extinctions started around the same time (i.e., eighteenth century), a logical expectation is that a large proportion of species may have gone extinct without ever having been recorded. Despite this evident and widely recognized assumption, the loss of undescribed species has never been estimated. We quantified this loss for several taxonomic groups and regions for which undescribed species extinctions are likely to have occurred. Across a wide range of taxonomic groups, we applied known extinction rates computed from recorded species losses to assumed exponential decay in the proportion of species remaining undiscovered. Because all previous modeling attempts to project total species richness implicitly assumed that undescribed species extinctions could be neglected, we also evaluated the effect of neglecting them. Finally, because we assumed constant description and extinction probabilities, we applied our model to simulated data that did not conform to this assumption. Actual species losses were severely underestimated by considering only known species extinctions. According to our estimates, the proportion of undiscovered extinct species over all extinctions ranged from 0.15 to 0.59, depending on the taxonomic group and the region considered. This means that recent extinctions may be up to twice as large as the number recorded. When species differed in their extinction or description probabilities, our model underestimated extinctions of undescribed species by up to 20%.

Variability in the growth rate of chub Leuciscus cephalus along a longitudinal river gradient.

An increase in individual growth rate of chub Leuciscus cephalus along a longitudinal river gradient of the Rhône River basin was observed and supported by significant differences between mean growth rates of successive river size groups. The potential implications of the results for studies on species traits variability along large-scale environmental gradients are discussed.

River hydrological seasonality influences life history strategies of tropical riverine fishes.

Under a particular set of selective forces, specific combinations of traits (strategies) will be favored in a given population, within the particular constraints of the considered species. For fishes, three demographic strategies have been suggested to result from adaptive responses to environmental predictability (i.e., seasonality): periodic, opportunistic and equilibrium [Winemiller KO, Rose KA (1992) Patterns of life-history diversification in North American fishes: implications for population regulation. Can J Fish Aquat Sci 49:2196-2218]. These strategies optimize fitness within predictable, unpredictable and stable systems, respectively. We tested these predictions of life history trait distribution along a gradient of hydrologic seasonality in West African tropical rivers at the drainage basin scale. We used logistic regression of species presence-absence data to test whether dominant life history traits of species caused community compositional change in response to a gradient of seasonality in hydrologic regime across basins. After accounting for taxonomic relatedness, species body size and statistical redundancy inherent to related traits, we found a higher proportion of species producing a great number of small oocytes, reproducing within a short period of time and presenting a low degree of parental care (the periodic strategy) in highly seasonal drainage basins (e.g., rivers with a short and predictable favorable season). Conversely, in more stable drainage basins (e.g., rivers with a wet season of several months), we observed a greater proportion of species producing small numbers of large oocytes, reproducing within a long period of time and providing parental care to their offspring (the equilibrium strategy). Our results suggest that distributions of tropical freshwater fishes at the drainage basin scale can be partly explained by the match between life history strategies and seasonality gradients in hydrological conditions.

Outcomes after laparoscopic Nissen fundoplication are not influenced by the pattern of reflux.

The purpose of this study was to compare the outcomes of patients with different types of gastroesophageal reflux disease (upright, supine, or bipositional) after laparoscopic Nissen fundoplication and determine if patients with upright reflux have worse outcomes. Two hundred and twenty-five patients with reflux confirmed by 24-h pH monitoring were divided into three groups based on the type of reflux present. Patients were questioned pre- and post-fundoplication regarding the presence and duration of symptoms (heartburn, regurgitation, dysphagia, cough and chest pain). Symptoms were scored using a 5-point scale, ranging from 0 (no symptom) to 4 (disabling symptom). Esophageal manometry and pH results were also compared. There was no statistically significant difference in lower esophageal sphincter length, pressure or function between the three groups. There was no significant difference in any of the postoperative symptom categories between the three groups. The type of reflux identified preoperatively does not have an adverse effect on postoperative outcomes after Nissen fundoplication and should not discourage physicians from offering antireflux surgery to patients with upright reflux.

Side-to-side stapled intra-thoracic esophagogastric anastomosis reduces the incidence of leaks and stenosis.

Trans-hiatal esophagectomy with a hand-sewn anastomosis was for 2 decades the preferred approach in our institution for patients with esophageal cancer. In our experience, this anastomotic technique was associated with a 12% leak rate and a 48% rate of stricture requiring dilatation. We sought to determine if a side-to-side intra-thoracic anastomosis was associated with a lower rate of anastomotic stricture and leak. Thirty-three consecutive patients with distal esophageal cancer or Barrett's esophagus with high grade dysplasia underwent a trans-thoracic esophagectomy with a side-to-side stapled intra-thoracic anastomosis. The overall morbidity was 27%, with no anastomotic stricture or leaks. One patient died (3%). The median time to the resumption of an oral diet was 7 days (range 5-28), and the median length of stay in hospital was 9 days (range 6-45). Trans-thoracic esophagectomy with a side-to-side stapled anastomosis is safe and it is associated with a very low rate of anastomotic complications. We consider this to be the procedure of choice for patients with distal esophageal cancers.

Effect of partial and total laparoscopic fundoplication on esophageal body motility.

BACKGROUND: Abnormal esophageal body motility often accompanies gastroesophageal reflux disease (GERD). Although the effect of surgery on the pressure and behavior of the lower esophageal sphincter (LES) has been extensively studied, it still is unclear whether a successful fundoplication improves esophageal peristalsis. METHODS: The pre- and postoperative esophageal manometries of 71 patients who underwent a successful laparoscopic fundoplication (postoperative DeMeester score < 14.7) were reviewed. The patients were grouped according to the type of fundoplication (partial vs total) and preoperative esophageal peristalsis (normal vs abnormal): group A (partial fundoplication and abnormal esophageal peristalsis; n = 16), group B (total fundoplication and normal peristalsis; n = 41), and group C (total fundoplication and abnormal peristalsis; n = 14). RESULTS: The LES pressure was increased in all the groups. A significant increase in amplitude of peristalsis was noted in groups A and C. Normalization of peristalsis was achieved in 31% of the group A patients and 86% of the group C patients. No changes occurred in group B. CONCLUSIONS: Laparoscopic fundoplication increased LES pressure and the strength of esophageal peristalsis in patients with abnormal preoperative esophageal motility. A total fundoplication resulted in normalization of peristalsis in the majority of patients.

Thoracoscopic resection of esophageal duplication cysts.

Esophageal duplication is a rare congenital esophageal disorder. Surgical excision is the standard treatment for symptomatic esophageal duplication cysts. Traditionally, the resection is accomplished via thoracotomy; however, a minimally invasive approach is possible, avoiding the long hospital stay, the discomfort and the long recovery time due to a thoracotomy. The authors describe two cases of esophageal duplication resected via a left thoracoscopic approach.

Timing of surgical intervention does not influence return of esophageal peristalsis or outcome for patients with achalasia.

BACKGROUND: It has been suggested that abnormal function of the lower esophageal sphincter is the primary abnormality in esophageal achalasia, and that the absence of esophageal peristalsis is secondary to the outflow obstruction caused by the lower esophageal sphincter. Furthermore, it has been proposed that early elimination of the resistance at the level of the gastroesophageal junction by surgical intervention could result in return of esophageal peristalsis. This study aimed to assess whether the timing of surgical intervention affects the return of esophageal peristalsis and the clinical outcome for patients with achalasia. METHODS: Between January 1991 and May 2003, 173 patients underwent a Heller myotomy by minimally invasive surgery for treatment of esophageal achalasia. Of these patients, 41 (24%) had pre- and postoperative esophageal manometry. These patients were divided into three groups based on the duration of symptoms: group A (10 patients; duration of symptoms 12 months group B (19 patients, duration of symptoms 12 to 60 months), and group C (12 patients; duration of symptoms longer than 60 months). RESULTS: The average duration of symptoms (dysphagia was present in all patients) was as follows: group A (8 +/- 4 months), group B, (35 +/- 16 months), and group C, (157 +/- 94 months). Vigorous achalasia was present in 40%, 21%, and 17% of the groups respectively. The differences between the groups were not significant. Postoperatively, improvement in esophageal motility was seen in no patient in group A, 1 patient (5%) in group B, and 1 patient (8%) in group C. Excellent or good results were obtained for 90% of the group A patients, 95% of group B patients, and 92% of the group C patients. Again, the differences were not significant. CONCLUSIONS: The results show that: a) the presence of vigorous achalasia is independent of symptoms duration; b) the timing of surgical intervention does not influence the return of peristalsis; and c) the results of a Heller myotomy are independent of symptoms duration.

Longevity genes in the nematode Caenorhabditis elegans also mediate increased resistance to stress and prevent disease.

More than 40 single-gene mutants in Caenorhabditis elegans have been demonstrated to lead to increased lifespan (a rigorous, operational test for being a gerontogene) of 20% or more; these are referred to collectively as 'Age' mutants. Age mutants must change key functions that are rate-limiting determinants of longevity; moreover, important genes can be identified independently of prior hypotheses as to actual mode of gene action in extending longevity and/or 'slowing' of ageing. These Age mutants define as many as nine (possibly) distinct pathways and/or modes of action, as defined by primary phenotype. Each of three well-studied mutants (age-1, clk-1, and spe-26) alters age-specific mortality rates in a fashion unique to itself. In age-1 mutants, the decreases in mortality rates are quite dramatic, with an almost tenfold drop in mortality throughout most of life. All Age mutants (so far without exception) increase the ability of the worm to respond to several (but not all) stresses, including heat, UV, and reactive oxidants. We have used directed strategies as well as random mutagenesis to identify novel genes that increase the worm's ability to resist stress. Two genes (daf-16 and old-1) are epistatic to the long-life phenotype of most mutants and also yield over-expression strains that are stress-resistant and long-lived. We have also used a variety of approaches to determine what transcriptional alterations are associated with increased longevity (and with ageing itself), including whole-genome expression studies using microarrays and GFP reporter constructs. We suggest that the role of the Age genes in both longevity and stress resistance indicates that a major evolutionary determinant of longevity is the ability to respond to stress. In mammals, both dietary restriction and hormesis are phenomena in which the endogenous level of resistance to stress has been upregulated; both of these interventions extend longevity, suggesting possible evolutionary conservation.

Relationship between increased longevity and stress resistance as assessed through gerontogene mutations in Caenorhabditis elegans.

We review the status of the hypothesis that interventions that increase the resistance to stress offer the potential for effective life prolongation and increased health. The work focuses on research in the nematode worm Caenorhabditis elegans and describes both published and unpublished results consistent with this hypothesis. Correlation between stress resistance and longevity among many gerontogene mutants is provided.

Age-specific demographic profiles of longevity mutants in Caenorhabditis elegans show segmental effects.

Demographic profiles of several single-gene longevity mutants of the nematode Caenorhabditis elegans reveal segmental (age-specific) effects on mortality. The mortality profiles of wild-type worms were examined across multiple replicate cultures containing 100,000 or more nematodes and found to be quite replicable, although clear environmental effects are routinely found. The combined profile of wild type was compared with those of three long-lived mutants to determine how age-specific mortality is altered by mutations in age-1, clk-1, or spe-26. In all four genotypes, death rates fit a two-stage Gompertz model better than a one-stage Gompertz; that is, mortality levels off at later ages. The largest genetic effect on mortality was that of an age-1 mutation, which lowered mortality more than fivefold at most later ages. In contrast, a spe-26 mutant had a tenfold lower mortality until approximately 2 weeks of age but ultimately achieved a higher mortality, whereas clk-1 mutants show slightly higher mortality than wild type during the fertile period, early in life, but ultimately level off at lower mortality. Each mutant thus has a distinctive profile of age-specific mortalities that could suggest the time of action of each gene.

Gerontogenes mediate health and longevity in nematodes through increasing resistance to environmental toxins and stressors.

More than 40 mutants in Caenorhabditis elegans have been demonstrated to lead to increased life span (a rigorous, operational test for being a gerontogene) of 20% or more ("Age" mutants). Age mutants alter rate-limiting determinants of longevity; moreover, important genes are identified independent of prior hypotheses as to actual mode of gene action in extending longevity and/or "slowing" aging. Age mutants define as many as nine (possibly) distinct pathways and/or modes of action, as defined by primary phenotype. Three well-studied mutants (age-1, clk-1, and spe-26) alter age-specific mortality rates in characteristic fashions; in age-1 mutants, especially, the changes in mortality rates are quite dramatic. All Age mutants (so far without exception) increase response to several (but not all) stresses, including heat, UV, and reactive oxidants. We have used directed strategies, as well as random mutagenesis, to identify novel genes increasing the worm's ability to resist stress. Two genes (daf-16 and old-1) yield over-expression strains that are stress resistant and long-lived. A variety of approaches to assess transcriptional alterations associated with increased longevity are underway. We suggest that the role of the Age genes in both longevity and stress resistance indicates that a major evolutionary determinant of longevity is the ability to respond to stress.

Molecular genetic mechanisms of life span manipulation in Caenorhabditis elegans.

Aging and a limited life span are fundamental biological realities. Recent studies have demonstrated that longevity can be manipulated and have revealed molecular mechanisms underlying longevity control in the soil nematode Caenorhabditis elegans. Signals from both neurons and the gonad appear to negatively regulate longevity. One tissue-specific signal involves an insulin-like phosphatidylinositol 3-OH kinase pathway, dependent upon the DAF-16 forkhead transcription factor. These signals regulate mechanisms determining longevity that include the OLD-1 (formerly referred to as TKR-1) receptor tyrosine kinase. Interestingly, increased resistance to environmental stress shows a strong correlation with life extension.

Manual compared with mechanical cervical oesophagogastric anastomosis: a randomised trial.

OBJECTIVE: To compare the short and medium term result of hand-sewn and stapled anastomoses after oesophagectomy. DESIGN: Randomised study. SETTING: Teaching hospital, Italy. SUBJECTS: 41 patients who required oesophagectomy between February 1993 and December 1996. INTERVENTIONS: Oesophagectomy and left cervical gastroplasty. MAIN OUTCOME MEASURES: Mortality and morbidity. RESULT: 21 patients were randomised to have the anastomosis hand-sewn, and 20 to have it stapled. The two groups were comparable. 3 patients died in hospital (2 in the hand-sewn and 1 in the stapled group), and the remainder were followed up a mean of 21 months (range 6-34). There was one clinical leak in the hand-sewn group compared with 3 in the stapled group, and 1 further radiological leak in the stapled group. 2 patients in the hand-sewn and 3 in the stapled group developed strictures. CONCLUSION: Though the numbers are too small to be assessed statistically, we think that these result are sufficient to persuade us that oesophagogastric anastomoses should be hand-sewn rather than stapled.

Experience of endoscopic ultrasound in staging adenocarcinoma of the cardia.

AIM: The introduction of endoscopic ultrasonography (EUS) has generally resulted in a more accurate assessment of gastrointestinal regional tumour stage. Knowing the stage and the extent of oesophageal involvement is extremely important as a guide to the choice of surgical approach in cardia cancer. The aim of this study was to evaluate the ability of EUS to accurately predict depth of tumour invasion (T), node involvement (N) and the tumour's invasion length along the oesophagus. MATERIAL AND METHODS: Thirty-five patients with adenocarcinoma of the cardia were studied by EUS and the EUS pre-operative findings were compared with the pathology findings. RESULTS: The overall accuracy in T staging was 55.2% (16/29 cases). The sensitivity in evaluating T1, T2 and T3 classes was 80%, 38.5% and 70%, respectively. The sensitivity was excellent in evaluating N0 class (100%) (5 cases), but it fell to 66.7% in N1 cases. EUS correctly determined the extent of oesophagus invasion in 75.9% (22/29) of cases; moreover, it had a very high accuracy in distinguishing between tumours with an oesophageal invasion greater or lower than 2 cm (93.1%) (27/29 cases). CONCLUSION: EUS proved to be useful in pre-operative staging of cardia adenocarcinoma and, in particular, in the pre-operative identification of the extent of oesophageal invasion.

Endoscopic ultrasonography in the staging of esophageal carcinoma after preoperative radiotherapy and chemotherapy.

BACKGROUND: In past years multimodal neoadjuvant treatment for carcinoma of the esophagus has been used with increased frequency. Staging of the neoplasm still remains fundamental in evaluating the response to therapy and in planning operation. The aim of the present study was to assess the accuracy of endoscopic ultrasonography (EUS) in a group of patients with squamous cell carcinoma of the thoracic esophagus after undergoing radiotherapy and chemotherapy. METHODS: Among a group of 111 patients with squamous cell carcinoma of the thoracic esophagus and treated with preoperative radiotherapy and chemotherapy, 87 were operated. In these patients it was possible to compare the results of EUS, with regard to depth of invasion of esophageal wall (T) and lymph node involvement (N), with the results of operation and histopathologic study. RESULTS: Feasibility of EUS before and after neoadjuvant treatment was 71.2% and 83.9%, respectively. The overall accuracy of EUS regarding the wall invasion was 47.9%. The more frequent error was overstaging, especially in patients with complete response and in patients with minimal residual disease. In the assessment of lymph node involvement, EUS showed an overall accuracy of 71.2% with a moderate kappa value. Sensitivity for N1 and NO was 73.7% and 68.6%, respectively. CONCLUSIONS: Endoscopic ultrasonography was feasible in most patients after preoperative radiotherapy and chemotherapy, but our study documented a worsening of accuracy of EUS in the evaluation of T attributable to the confounding presence of radiation fibrosis and soft tissue reaction after radiotherapy and chemotherapy.

A symposium on psychotherapy in the age of managed care.

This article is based upon a symposium presented at Vanderbilt University Medical Center on the Department of Psychiatry's 50th anniversary (September 20, 1997). The panel of psychotherapy scholar-clinicians discusses issues including: whether or not managed care and psychotherapy are compatible; the relevance of the Consumer Reports' psychotherapy study to MCOs' emphasis on brief therapy; how MCOs impact upon the therapist-patient relationship; the effects of MCOs on the psychotherapist's personal and professional identity; and training psychotherapists in the era of managed care. The paper is dedicated to Pietro Castelnuovo-Tedesco, M.D., Vanderbilt's Blakemore Professor of Psychiatry, who died on January 24, 1998.

Induction chemo-radiotherapy for squamous cell carcinoma of the thoracic esophagus: long-term results of a phase II study.

BACKGROUND: This study was done to evaluate the results of the combined use of chemo- and radiotherapy before surgery in a group of patients with squamous cell esophageal carcinoma after a median follow-up period of more than 5 years. METHODS: Between June 1987 and January 1995, 111 patients with squamous cell carcinoma of the thoracic esophagus were submitted to a preoperative course of radiotherapy (3000 cGy) and chemotherapy (cisplatin and 5-FU) before surgery in the First Division of General Surgery at the University of Verona. RESULTS: The neoadjuvant treatment was completed in 90.9% of the cases (101/111). After an average of 29 days, 87 patients underwent surgery (operability rate: 78.3%) and, of these, 80 underwent esophagectomy (resectability rate: 91.9%). Histopathologic studies showed no residual disease in the specimen (T0) in 17 cases (21.2%), only microscopic clusters of neoplastic cells within the esophageal wall (Minimal Residual Disease, MRD) in 14 cases (17.5%) and in 5 cases the tumor did not extend beyond the submucosal layer (T1). The median overall survival time of the 111 patients who were eligible for the study protocol was 14 months, and the 2- and 5-year survival rates were 32.0% and 17.5%, respectively. Kaplan-Meier determination of survival showed a statistically significant difference between the good responders (T0, T1, and MRD) to the neoadjuvant treatment and the remaining cases. The 2- and 5-year survival rates were 50.3% and 34.9%, respectively, in the good responder group compared with 26.7% and 10.7%, respectively, in the other cases, with a median survival time of 24 months vs. 13 months, respectively. CONCLUSIONS: The neoadjuvant treatment showed promising results, especially in the group of patients that had a good response. The identification of these patients may be the key to selecting which patients should be submitted to preoperative radio- and chemotherapy.

[Immunohistochemical study on the prognostic value of the expression of laminin and Ki-67 receptors in advanced gastric cancer]. / Studio immunoistochimico sul valore prognostico dell'espressione del recettore per la laminina e del Ki-67 nel cancro gastrico avanzato.

The expression of 67-KDa laminin receptor (LR) was investigated in a group of 75 patients who underwent curative gastrectomy for advanced gastric cancer, with special reference to the possible role in the tumor progression and in the overall survival. In 56 out of these 75 patients also the prognostic significance of proliferative activity was investigated using the monoclonal antibody Ki-67. The tumor LR expression and the Ki-67 labeling index (Ki-67 LI) were immunohistochemically determined in paraffin-embedded sections using the avidin-biotin immunoperoxidase method. The cumulative 5-years survival rate was 75.1% for patients without expression of LR, 52.6% for those with positive LR expression. Significant association between LR expression and depth of tumor invasion (p = 0.022) was found. By univariate analysis the presence of laminin receptor seemed to be associated with an higher risk of death (RR1.73-95% C.I. 0.71-4.20), but this effect disappeared after controlling for depth of tumor invasion. There was no significant relationship between the Ki-67 LI and wall invasion (p = 0.80) or nodal status (p = 0.73). The cumulative 5-year survival rates (95% CI) were 61.0% (35.3-79.2) in patients with Ki-67 index < 10%, 52.4% (29.7-70.9) with Ki-67 index = 10%-40%, 52.9% (27.6-73.0) with Ki-67 index > 40% and the differences were not statistically significant (p = 0.93). Also in multivariate analysis the proliferative activity did not independently affect survival (p = 0.98). An interaction between Ki-67 index and age was found and Ki-67 index > 40% was significantly associated with a poor prognosis in patients over 70 years old old (p = 0.002). In conclusion, tumor expression of laminin receptor could be correlated with gastric cancer aggressiveness, however its prognostic significance is already provided by depth of tumor invasion. The proliferative activity, determined with the monoclonal antibody Ki-67, does not seems to influence the survival except in elderly patients (> or = 70 years old).