Rationalization may improve predictability rather than accuracy.

We present a theoretical and an empirical challenge to Cushman's claim that rationalization is adaptive because it allows humans to extract more accurate beliefs from our non-rational motivations for behavior. Rationalization sometimes generates more adaptive decisions by making our beliefs about the world less accurate. We suggest that the most important adaptive advantage of rationalization is instead that it increases our predictability (and therefore attractiveness) as potential partners in cooperative social interactions.

Moral externalization and normativity: The errors of our ways.

I respond to the many thoughtful suggestions and concerns of my commentators on a wide variety of questions. These include whether moral norms form a unified category, whether they have a distinctive phenomenology, and/or whether moral normativity is a cultural construct; whether moral externalization is necessary for correlated interaction or human prosociality; precisely how such externalization generates correlated interactions among prosocial agents; and whether there are any convincing alternative explanations for it.

The difference between ice cream and Nazis: Moral externalization and the evolution of human cooperation.

A range of empirical findings is first used to more precisely characterize our distinctive tendency to objectify or externalize moral demands and obligations, and it is then argued that this salient feature of our moral cognition represents a profound puzzle for evolutionary approaches to human moral psychology that existing proposals do not help resolve. It is then proposed that such externalization facilitated a broader shift to a vastly more cooperative form of social life by establishing and maintaining a connection between the extent to which an agent is herself motivated by a given moral norm and the extent to which she uses conformity to that same norm as a criterion in evaluating candidate partners in social interaction generally. This connection ensures the correlated interaction necessary to protect those prepared to adopt increasingly cooperative, altruistic, and other prosocial norms of interaction from exploitation, especially as such norms were applied in novel ways and/or to novel circumstances and as the rapid establishment of new norms allowed us to reap still greater rewards from hypercooperation. A wide range of empirical findings is then used to support this hypothesis, showing why the status we ascribe to moral demands and considerations exhibits the otherwise puzzling combination of objective and subjective elements that it does, as well as showing how the need to effectively advertise our externalization of particular moral commitments generates features of our social interaction so familiar that they rarely strike us as standing in need of any explanation in the first place.

More-than-minimal-trauma fractures are associated with low bone density: an 8-year prospective study.

Few studies have examined the relationship between more-than-minimal-trauma fractures and bone density. This study demonstrated that more-than-minimal-trauma fractures are associated with lower bone density similar to that seen in minimal trauma fractures. Men and women over 50 years with a more-than-minimal-trauma fracture should be investigated to exclude low bone density. INTRODUCTION: The aim of this study was to assess the prevalence and predictors of low bone density in men and women with more-than-minimal-trauma fractures. METHODS: In an Australian hospital, 630 community-dwelling men and women, 20 years of age or older, sustained a fracture due to more-than-minimal-trauma (force greater than a fall from standing height but less than high trauma). We studied 349 individuals who agreed to have a bone mineral density (BMD) scan. These participants were compared with 472 men and women with minimal trauma fractures. RESULTS: Men and women with more-than-minimal-trauma fractures had significantly lower bone density than expected for their age, gender and weight (Z-scorespine = -0.4 SD, 95 % confidence interval (CI), -0.5 to -0.3; Z-scorehip = -0.5 SD, 95 % CI, -0.6 to -0.4). Almost 1 in 4 of those over 50 years of age had osteoporosis by BMD criteria. The independent predictors of low bone density (T-score <-2.0 SD) were age equal to or over 50 years (odds ratio (OR) = 5.97, 95 % CI, 3.34 to 10.65), low body weight <20 kg/m2 (OR = 3.44, 95 % CI, 1.32 to 8.94), a prior minimal trauma fracture (OR = 2.76, 95 % CI, 1.17-6.52) and in those over 50 years of age, an osteoporosis-associated condition (OR = 4.51, 95 % CI, 1.69 to 12.06). Men and women with more-than-minimal-trauma fractures had similar bone density (Z-score) compared to those with minimal trauma fractures. CONCLUSIONS: Men and women over 50 years with a more-than-minimal-trauma fracture, especially those with low body weight, prior minimal trauma fracture or an osteoporosis-associated condition, should be investigated to exclude low bone density and its associated risk of subsequent fractures.

Increased operant responding for ethanol in male C57BL/6J mice: specific regulation by the ERK1/2, but not JNK, MAP kinase pathway.

RATIONALE: Extracellular signal-regulated protein kinase (ERK(1/2)) is a member of the mitogen-activated protein kinase (MAPK) signaling pathway and a key molecular target for ethanol (EtOH) and other drugs of abuse. OBJECTIVE: The aim of the study was to assess the role of two MAPK pathways, ERK(1/2) and c-Jun N-terminal kinase (JNK), on the modulation of EtOH and sucrose self-administration. MATERIALS AND METHODS: C57BL/6J mice were trained to lever press on a fixed-ratio 4 schedule with 9% EtOH/2% sucrose, or 2% sucrose, as the reinforcer. In experiments 1 and 2, mice were injected with the MEK(1/2) inhibitor SL 327 (0-100 mg/kg) and the JNK inhibitor AS 6012452 (0-56 mg/kg) prior to self-administration. In experiment 3, SL 327 (0-100 mg/kg) was administered prior to performance on a progressive ratio (PR) schedule of EtOH reinforcement. In experiment 4, SL 327 and AS 601245 were injected 2 h before a locomotor test. RESULTS: SL 327 (30 mg/kg) significantly increased EtOH self-administration without affecting locomotion. Higher doses of SL 327 and AS 601245 reduced EtOH-reinforced responding and locomotor activity. Reductions of both ligands on sucrose self-administration were due to decreases in motor activity. SL 327 pretreatment had no effect on PR responding. CONCLUSIONS: ERK(1/2) activity is more directly involved in modulating the reinforcing properties of EtOH than JNK activity due to its selective potentiation of EtOH-reinforced responding. The specificity of this effect to EtOH self-administration, rather than sucrose self-administration, suggests that the mechanism by which ERK(1/2) increases EtOH-reinforced responding does not generalize to all reinforcing solutions and is not due to increased motivation to consume EtOH.

August Weismann's theory of the germ-plasm and the problem of unconceived alternatives.

I have argued elsewhere that scientific realism is most significantly challenged neither by traditional arguments from underdetermination of theories by the evidence, nor by the traditional pessimistic induction, but by a rather different historical pattern: our repeated failure to conceive of alternatives to extant scientific theories, even when those alternatives were both (1) well-confirmed by the evidence available at the time and (2) sufficiently scientifically serious as to be later embraced by actual scientific communities. Here I use August Weismann's defense of his influential germ-plasm theory of inheritance to support my claim that this pattern characterizes the history of theoretical scientific investigation generally. Weismann believed that the germ-plasm must become disintegrated into its constituent elements over the course of development, I argue, only because he failed to conceive of any possible alternative mechanism of ontogenetic differentiation. This and other features of the germ-plasm theory, I suggest, reflect a still more fundamental failure to imagine that the germ-plasm might be a productive rather than expendable resource for the cell. Weismann's case provides impressive support for the problem of unconceived alternatives while rendering its challenge to scientific realism deeper and sharper in a number of important ways.

Similar early clinical presentations in familial and non-familial frontotemporal dementia.

BACKGROUND: It is unclear whether there are early clinical features that can distinguish between patients with familial and non-familial frontotemporal dementia (FTD). OBJECTIVE: To compare the clinical features of FTD cases who have tau gene mutations with those of cases with a family history of FTD but no tau gene mutation, and with sporadic cases with neither feature. METHODS AND RESULTS: Comparisons of the behavioural, cognitive, and motor features in 32 FTD patients (five positive for tau gene mutations, nine familial but tau negative, and 18 tau negative sporadic) showed that age of onset and duration to diagnosis did not differ between the groups. Apathy was not observed in tau mutation positive cases, and dysexecutive signs were more frequent in familial tau mutation negative cases. Memory deficits and behavioural changes were common in all groups. CONCLUSIONS: In comparison with other neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease, neither tau gene mutations nor strong familial associations confer earlier disease susceptibility.

Surgical approaches to pancreatic cancer.

Pancreatic cancer continues to be a significant health problem. Recent advances in medical technologies allow patients with pancreatic cancer to undergo diagnosis, staging, treatment, and palliation, and to minimize the traditional use of laparotomy as a method of obtaining information to facilitate treatment planning. Pancreatic surgery, which can impact duration and quality of life, can be reserved for that subset of patients likely to benefit from a surgical approach tailored to the specific needs of the individual patient.

High-risk sexual behaviors among adolescents engaged through a street-based peer outreach program--(the Adolescent HIV Project).

On-the-street peer based programs can overcome barriers and successfully engage teens in HIV counseling and testing. This initiative combines on-the-street peer outreach with on-the-street HIV testing in a mobile counseling and testing van. A survey was conducted to measure HIV risk behaviors concern about HIV infection. In year one, the program engaged 1550 youth. Of these, 666 completed HIV counseling and testing. Only 18% indicated that they had not had unprotected sexual intercourse in the preceding year. Thirty-nine percent of the males and 52% of the females had caused or been pregnant. Sixty-six percent of the males and 53% of the females believed that they could become HIV infected. Fifty-three percent of the male and 75% of the female respondents had had a previous HIV test. However concern about HIV did not significantly decrease the prevalence of HIV risk behaviors. Peer outreach and on-the-street counseling and testing is a successful method of increasing HIV testing among high risk youth. Youth are concerned about HIV infection but that concern does not translated into a change in risk behaviors.

Cost and utilization impact of a clinical pathway for patients undergoing pancreaticoduodenectomy.

BACKGROUND: When implemented in several common surgical procedures, clinical pathways have been reported to reduce costs and resource utilization, while maintaining or improving patient care. However, there is little data to support their use in more complex surgery. The objective of this study was to determine the effects of clinical pathway implementation in patients undergoing elective pancreaticoduodenectomy (PD) on cost and resource utilization. METHODS: Outcome data from before and after the development of a clinical pathway were analyzed. The clinical pathway standardized the preoperative outpatient care, critical care, and postoperative floor care of patients who underwent PD. An independent department determined total costs for each patient, which included all hospital and physician costs, in a blinded review. Outcomes that were examined included perioperative mortality, postoperative morbidity, length of stay, readmissions, and postoperative clinic visits. RESULTS: From January, 1996 to December, 1998, 148 consecutive patients underwent PD or total pancreatectomy; 68 before pathway development (PrePath) and 80 after pathway implementation (PostPath). There were no significant differences in patient demographics, comorbid conditions, underlying diagnosis, or use of neoadjuvant therapy between the two groups. Mean total costs were significantly reduced in PostPath patients compared with PrePath patients ($36,627 vs. $47,515; P = .003). Similarly, mean length of hospital stay was also significantly reduced in PostPath patients (13.5 vs. 16.4 days; P = .001). The total cost differences could not be attributed solely to differences in room and board costs. Cost and length-of-stay differences remained when outliers were excluded from the analysis. Despite these findings, there were no significant differences between PrePath and PostPath patients in terms of perioperative mortality (3% vs. 1%), readmissions within 1 month of discharge (15% vs. 11%), or mean number of clinic visits within 90 days of discharge (3.3 vs. 3.4 visits). CONCLUSIONS: The establishment of a clinical pathway for PD patients dramatically reduced costs and resource utilization without any apparent detrimental effect on quality of patient care. These findings support the implementation of clinical pathways for PD patients, as well as investigation into pathway care for other complex surgical procedures.

A biomechanical comparison of the Z step-cut and basilar crescentic osteotomies of the first metatarsal.

The basilar crescentic osteotomy is a popular procedure for the correction of moderate to severe hallux valgus deformity. Dorsiflexion due to malposition of the osteotomy, fixation failure, or late contracture of the soft tissues can lead to lateral metatarsalgia. This study compares the mechanical properties of the Z step cut osteotomy Scarff to those of the crescentic osteotomy in cantilever-bending. The ultimate load, maximum bending moment and energy absorbed were significantly greater for the Scarff osteotomy compared to those in the crescentic osteotomy (p < 0.001). Values for stiffness did not differ between the two osteotomies. Failure of the cortical bone-bridge between the screw-hole and the osteotomy was observed in all crescentic osteotomies, while fracture of the proximal dorsal bridge was seen in all Scarff osteotomies.

Relative contributions of technetium Tc 99m sestamibi scintigraphy, intraoperative gamma probe detection, and the rapid parathyroid hormone assay to the surgical management of hyperparathyroidism.

HYPOTHESIS: Technetium Tc 99m sestamibi scintigraphy, intraoperative gamma probe detection, and the rapid parathyroid hormone assay have been used to permit a directed operation in patients with hyperparathyroidism. We hypothesized that the coordinated use of these techniques might be particularly useful in patients who require a second operation for hyperparathyroidism. DESIGN: Retrospective analysis was performed to determine the specific contribution of these technologies to the surgical management of patients with hyperparathyroidism who underwent evaluation by at least 2 of these techniques between April 1996 and October 1999. SETTING: Patients were evaluated and treated by an endocrine tumor surgery group within a tertiary care referral center. PATIENTS: Coordinated application of 99mTc-sestamibi scintigraphy, intraoperative gamma probe detection, and/or the rapid parathyroid hormone assay was performed in 32 patients. RESULTS: Twenty-eight of 32 patients had primary hyperparathyroidism, 3 had multiple endocrine neoplasia type 1, and 1 had secondary hyperparathyroidism. The surgical procedure was an initial cervical exploration in 19 and a second operative procedure in 13. Parathyroidectomy was successful in all patients. A directed anatomic operation was performed in 24 patients, including 11 patients who underwent second operative procedures and 9 patients who underwent minimally invasive procedures under local anesthesia. A directed operation was facilitated by sestamibi scan in 22 of 24 patients, intraoperative gamma probe detection in 5 of 23 patients, and the rapid parathyroid hormone assay in 15 of 15 patients. CONCLUSIONS: Coordinated application of 99mTc-sestamibi scintigraphy, intraoperative gamma probe detection, and the rapid parathyroid hormone assay allows for successful directed reoperative parathyroidectomy; a minimally invasive procedure may be performed in selected patients.

Progressive supranuclear palsy pathology caused by a novel silent mutation in exon 10 of the tau gene: expansion of the disease phenotype caused by tau gene mutations.

Genetic mutations in the tau gene on chromosome 17 are known to cause frontotemporal dementias. We have identified a novel silent mutation (S305S) in the tau gene in a subject without significant atrophy or cellular degeneration of the frontal and temporal cortices. Rather the cellular pathology was characteristic of progressive supranuclear palsy, with neurofibrillary tangles concentrating within the subcortical regions of the basal ganglia. Two affected family members presented with symptoms of dementia and later developed neurological deficits including abnormality of vertical gaze and extrapyramidal signs. The third presented with dystonia of the left arm and dysarthria, and later developed a supranuclear gaze palsy and falls. The mutation is located in exon 10 of the tau gene and forms part of a stem-loop structure at the 5' splice donor site. Although the mutation does not give rise to an amino acid change in the tau protein, functional exon-trapping experiments show that it results in a significant 4.8-fold increase in the splicing of exon 10, resulting in the presence of tau containing four microtubule-binding repeats. This study provides direct molecular evidence for a functional mutation that causes progressive supranuclear palsy pathology and demonstrates that mutations in the tau gene are pleiotropic.

Screening for MEN1 mutations in patients with atypical endocrine neoplasia.

BACKGROUND: Most patients from typical multiple endocrine neoplasia type 1 (MEN1) kindreds harbor mutations in the MEN-1 gene, MEN1. We hypothesized that some patients with atypical endocrine neoplasia would also have mutations in MEN1. METHODS: DNA sequencing analysis of mutations in the coding region of MEN1 was performed with genomic DNA obtained from peripheral blood lymphocytes in a total of 21 patients who had: typical MEN1 (n = 8), clinical features suggestive of MEN1 but without a family history of endocrinopathy (n = 7), and atypical endocrine neoplasia and a family history of endocrinopathy suggestive of MEN1 (n = 6). RESULTS: All 8 patients with typical MEN1 had mutations in MEN1. None of the 7 patients with features of MEN1, but without a family history of endocrinopathy, had a MEN1 mutation. In contrast, 4 of 6 patients with atypical endocrine neoplasia that included components of MEN1 and a family history of endocrinopathy had mutations in MEN1, including 2 patients with pheochromocytoma. CONCLUSIONS: Genomic mutations in MEN1 may frequently be identified in patients with atypical endocrine neoplasia, especially in the setting of a family history of endocrinopathy. Atypical presentations of MEN1 may include pheochromocytoma.

Stereological estimation of the total number of neurons in the murine hippocampus using the optical disector.

Using a stereological method, the optical disector, we examined three inbred strains of mice (NZB/BINJ, DBA/2, and C57BL/6J) for morphological differences in volume, neuronal number, and density of the pyramidal cell and dentate gyrus granule cell layers of the hippocampus. We found significant differences in volume and neuronal number for both regions between the three strains at 9 weeks of age, but only modest differences in neuronal density. The left dentate volume was 90% larger in the NZB strain and 70% greater in the DBA strain (P<0.0001), and the left pyramidal cell layer was 144% larger in the NZB strain and 150% larger in the DBA strain, than in the B6 strain (P<0.0001). Neuron number in the left dentate was 81% greater in NZB and 37% greater in DBA (P<0.001), and in the left pyramidal cell layer 118% greater in the NZB and 92% greater in the DBA (P<0.01). Differences in neuronal density of the left dentate were not significant (P = 0.060, ns). For the left pyramidal cell layer, neuronal density was 14% greater in B6 and 34% greater in NZB than the DBA strain (P = 0.016). No significant differences were found in left-right laterality, or according to sex. We found that strain accounted for 60% of the variance in hippocampal volume and 44% of neuron number. These differences thus mainly reflect genetic variation in hippocampal volume and may have important implications for brain evolution, behaviour, and human diseases where hippocampal degeneration is involved.

Pre-operative assessment for ophthalmic patients.

This article discusses the role of pre-operative assessment for ophthalmic patients and outlines the role nurses can play in patients' preparation for day surgery.

Analysis of Australian Crohn's disease pedigrees refines the localization for susceptibility to inflammatory bowel disease on chromosome 16.

A number of localizations for the putative susceptibility gene(s) have been identified for both Crohn's disease and ulcerative colitis. In a genome wide scan, Hugot et al. (1996) identified a region on chromosome 16 which appeared to be responsible for the inheritance of inflammatory bowel disease in a small proportion of families. Subsequent work has suggested that this localization is important for susceptibility to Crohn's disease rather than ulcerative colitis (Ohmen et al. 1996; Parkes et al. 1996). We investigated the contribution of this localization to the inheritance of inflammatory bowel disease in 54 multiplex Australian families, and confirmed its importance in a significant proportion of Crohn's disease families; we further refined the localization to a region near to D16S409, obtaining a maximum LOD score of 6.3 between D16S409 and D16S753.

Prospective, randomized trial of octreotide to prevent pancreatic fistula after pancreaticoduodenectomy for malignant disease.

OBJECTIVE: This study was conducted to determine whether the perioperative administration of octreotide decreases the incidence of pancreatic anastomotic leak after pancreaticoduodenectomy for malignancy. SUMMARY BACKGROUND DATA: Three multicenter, prospective, randomized trials concluded that patients who receive octreotide during and after pancreatic resection have a reduction in the total number of complications or a decreased incidence of pancreatic fistula. However, in the subset of patients who underwent pancreaticoduodenectomy for malignancy, either no analysis was performed or no benefit from octreotide could be demonstrated. METHODS: A single-institution, prospective, randomized trial was conducted between June 1991 and December 1995 involving 120 patients who were randomized to receive octreotide (150 microg subcutaneously every 8 hours through postoperative day 5) or no further treatment after pancreaticoduodenectomy for malignancy. The surgical technique was standardized, and the pancreaticojejunal anastomosis was created using the duct-to-mucosa or invagination technique. RESULTS: The two patient groups were similar with respect to patient demographics, treatment variables, and histologic diagnoses. The rate of clinically significant pancreatic leak was 12% in the octreotide group and 6% in the control group (p = 0.23). Perioperative morbidity was 30% and 25%, respectively. Patients who underwent reoperative pancreaticoduodenectomy had an increased incidence of pancreatic anastomotic leak, whereas those who received preoperative chemoradiation had a decreased incidence of pancreatic anastomotic leak. CONCLUSIONS: The routine use of octreotide after pancreaticoduodenectomy for malignancy cannot be recommended.