New insights in the probability distributions of wave-by-wave overtopping volumes at vertical breakwaters.

Advances in the development of prediction tools for wave overtopping allow now for overtopping volumes to be estimated with good accuracy, with the combined use of mean overtopping rates and maximum wave by wave overtopping volumes in a sequence of wave overtopping events. While previous literature has tended to focus on mean overtopping rates at coastal structures, limited studies have investigated the wave by wave overtopping volumes at coastal sea defences; in particular, a paucity of studies have focussed on the prediction of the shape parameter in the Weibull distribution (i.e., Weibull b) of overtopping volumes. This study provides new insights on the probability distribution of individual wave overtopping volumes at plain vertical seawalls by analysing the measured Weibull b values derived from a series of laboratory experiments on seawalls performed on a wide range of wave conditions and crest freeboards. The influence of wave conditions (wave steepness, significant wave height), structural parameters (crest freeboard, toe water depth), impulsiveness, probability of overtopping waves, and overtopping discharge on Weibull b parameter were examined, and then compared with the well-established empirical formulae. For the conditions covered within this study, it was found that the probability distribution of wave-by-wave overtopping volumes follow a 2-parameter Weibull distribution. No apparent differences in Weibull b values were reported with the variation of incident wave steepness and impulsiveness parameter. Results of this study revealed that Weibull b values at vertical walls, subjected to non-impulsive wave conditions, can be predicted reasonably well using relative freeboard and relative overtopping rates. A new unified formula is proposed for the estimation of Weibull b values at vertical walls under impulsive and non-impulsive wave attack.

Combined total hip and knee arthroplasty during the same hospital admission: is it safe?.

AIMS: The purpose of this study was to compare outcomes of combined total joint arthroplasty (TJA) (total hip arthroplasty (THA) and total knee arthroplasty (TKA) performed during the same admission) versus bilateral THA, bilateral TKA, single THA, and single TKA. Combined TJAs performed on the same day were compared with those staged within the same admission episode. PATIENTS AND METHODS: Data from the National (Nationwide) Inpatient Sample recorded between 2005 and 2014 were used for this retrospective cohort study. Postoperative in-hospital complications, total costs, and discharge destination were reviewed. Logistic and linear regression were used to perform the statistical analyses. p-values less than 0.05 were considered statistically significant. RESULTS: Combined TJA was associated with increased risk of deep vein thrombosis, prosthetic joint infection, irrigation and debridement procedures, revision arthroplasty, length of stay (LOS), and in-hospital costs compared with bilateral THA, bilateral TKA, single THA, and single TKA. Combined TJA performed on separate days of the same admission showed no statistically significant differences when compared with same-day combined TJA, but trended towards decreased total costs and total complications despite increased LOS. CONCLUSION: Combined TJA is associated with increased in-hospital complications, LOS, and costs. We do not recommend performing combined TJA during the same hospital stay. Cite this article: Bone Joint J 2019;101-B:573-581.

A Primer on Foraging and the Explore/Exploit Trade-Off for Psychiatry Research.

Foraging is a fundamental behavior, and many types of animals appear to have solved foraging problems using a shared set of mechanisms. Perhaps the most common foraging problem is the choice between exploiting a familiar option for a known reward and exploring unfamiliar options for unknown rewards-the so-called explore/exploit trade-off. This trade-off has been studied extensively in behavioral ecology and computational neuroscience, but is relatively new to the field of psychiatry. Explore/exploit paradigms can offer psychiatry research a new approach to studying motivation, outcome valuation, and effort-related processes, which are disrupted in many mental and emotional disorders. In addition, the explore/exploit trade-off encompasses elements of risk-taking and impulsivity-common behaviors in psychiatric disorders-and provides a novel framework for understanding these behaviors within an ecological context. Here we explain relevant concepts and some common paradigms used to measure explore/exploit decisions in the laboratory, review clinically relevant research on the neurobiology and neuroanatomy of explore/exploit decision making, and discuss how computational psychiatry can benefit from foraging theory.

Vertical variation of mixing within porous sediment beds below turbulent flows.

River ecosystems are influenced by contaminants in the water column, in the pore water and adsorbed to sediment particles. When exchange across the sediment-water interface (hyporheic exchange) is included in modeling, the mixing coefficient is often assumed to be constant with depth below the interface. Novel fiber-optic fluorometers have been developed and combined with a modified EROSIMESS system to quantify the vertical variation in mixing coefficient with depth below the sediment-water interface. The study considered a range of particle diameters and bed shear velocities, with the permeability Péclet number, PeK between 1000 and 77,000 and the shear Reynolds number, Re*, between 5 and 600. Different parameterization of both an interface exchange coefficient and a spatially variable in-sediment mixing coefficient are explored. The variation of in-sediment mixing is described by an exponential function applicable over the full range of parameter combinations tested. The empirical relationship enables estimates of the depth to which concentrations of pollutants will penetrate into the bed sediment, allowing the region where exchange will occur faster than molecular diffusion to be determined.

Benign papilloma diagnosed on image-guided 14 G core biopsy of the breast: effect of lesion type on likelihood of malignancy at excision.

AIM: To ascertain the negative predictive value (NPV) for atypia and malignancy of 14 G core biopsy of papillomas and to determine whether lesion type influences the likelihood of malignancy at lesion excision. MATERIALS AND METHODS: Ninety-six lesions with a 14 G core biopsy diagnosis of benign papilloma without atypia in 95 women were included. The imaging features (mass or microcalcification), biopsy mode, and number of core samples taken were documented. All patients subsequently underwent lesion excision with either extensive vacuum-assisted biopsy (VAB; 72 lesions) or surgery (24 lesions). Mammographic follow-up of at least 2 years was available for 32 lesions that were benign at VAB. RESULTS: Atypia or malignancy was found more commonly in association with microcalcification (six of 29 lesions: 21%; median number of nine 14 G cores) than a mass (five of 67 lesions: 7%; median number of three 14 G cores), although the difference does not reach statistical significance (p = 0.088). The NPV of a 14 G core biopsy diagnosis of papilloma for atypia or malignancy is 89% (85/96). Disease underestimation may be more common in microcalcification lesions despite the greater number of cores obtained. CONCLUSION: Excision (using VAB or surgically) of all papillomas diagnosed as benign on 14 G needle core biopsy is recommended. Surgery may be more appropriate than VAB for some microcalcification lesions unless they are small and can be confidently removed in their entirety using VAB.

Criteria for the safe avoidance of needle sampling in young women with solid breast masses.

AIM: To establish clinical and ultrasonic criteria by which needle sampling can be safely avoided in young women with solid breast masses. MATERIALS AND METHODS: The databases of a large hospital were searched for breast cancers, phyllodes tumours, and papillomas diagnosed in women below the age of 30 years. In addition, the clinical and sonographic findings in female patients less than 25 years of age presenting with a solid breast mass over a 1-year period were reviewed. RESULTS: Nine women with breast cancer, seven with phyllodes, and six with papillomas were found. No delayed diagnoses in those who had ultrasound would have been made if the following criteria had been applied to avoid needle sampling: age less than 25 years; no known risk factors for breast malignancy; mass not rapidly enlarging; smooth discrete mobile mass on clinical examination, or lesion impalpable; well-defined homogeneously isoechoic or mildly hypoechoic solid mass; less than 3 cm in greatest dimension; ovoid shape, aligned parallel to the skin surface; smooth or gently lobulated contour (two or three lobulations only; no microlobulation); thin echogenic pseudocapsule; no calcification; no acoustic shadowing. Needle sampling could have been safely avoided in approximately two-thirds of the women reviewed below the age of 25 with a solid breast mass. CONCLUSION: Application of the proposed criteria would spare a significant number of young women unnecessary needle sampling.

Skyrme-Hartree-Fock-Bogoliubov nuclear mass formulas: crossing the 0.6 MeV accuracy threshold with microscopically deduced pairing.

We present a new Skyrme-Hartree-Fock-Bogoliubov nuclear-mass model in which the contact-pairing force is constructed from microscopic pairing gaps of symmetric nuclear matter and neutron matter calculated from realistic two- and three-body forces, with medium-polarization effects included. With the pairing being treated more realistically than in any of our earlier models, the rms deviation with respect to essentially all the available mass data falls to 0.581 MeV, the best value ever found within the mean-field framework. Since our Skyrme force is also constrained by the properties of pure neutron matter, this new model is particularly well suited for application to astrophysical problems involving a neutron-rich environment, such as the elucidation of the r process of nucleosynthesis, and the description of supernova cores and neutron-star crusts.

Nonradiative de-excitation mechanisms in long-lived erbium(III) organic compounds ErxY1-x[(p-CF3-C6F4)2PO2]3.

We have performed a spectroscopic study of ErxY1-x[(p-CF3-C6F4)2PO2]3 aimed at understanding nonradiative de-excitation mechanisms. These fluorinated compounds have a long lifetime for the erbium 4I13/2-->4I15/2 emission at lambda approximately 1540 nm, but the lifetime increases with decreasing x. We have studied the lifetime as a function of morphology, temperature, and high hydrostatic pressure. We have demonstrated the occurrence of energy migration and calculated the corresponding activation energy. Moreover, using high pressure techniques, we provide evidence that cross-relaxation involving energy transfer from an excited erbium in the 4I13/2 promoting a neighbor in the same state to 4I9/2 is the dominant mechanism at ambient conditions for short erbium-erbium distances. The model explains the observed dynamics of excited states in the series and is tested against the Yb[(p-CF3-C6F4)2PO2]3 compound.

The behaviour of linear alkyl benzene sulphonate under direct discharge conditions in Vientiane, Lao PDR.

Direct discharge of untreated sewage to surface waters is a common practice in many parts of the world. However, relatively little is known about the behaviour of synthetic organic pollutants under these conditions. This paper describes a sampling campaign designed to track changes in water quality in a surface water system in Vientiane (Lao PDR) receiving significant quantities of untreated waste water. The study was based on following in-channel transport using a fluorescent tracer injected as a pulse, with a focus on the anionic surfactant linear alkylbenzene sulphonate (LAS) and ammonia. Water samples were collected at a number of stations with sampling times estimated to coincide with solute time-of-travel. The reduction in LAS concentration with flow-time could be approximated by first-order kinetics with a half life of about 7 h. Free ammonia concentrations decreased more slowly than LAS and remained above the level believed to be toxic for sensitive aquatic species along the entire channel. Changes in the ratios of LAS alkyl chain homologues to total LAS concentrations suggest a preferential removal of longer chain lengths. The role of biodegradation in the removal of LAS was confirmed by the presence of LAS metabolites (sulphophenylcarboxylates, SPCs) which increased systematically (as a fraction of LAS remaining) with flow-time.

A Dukes/Jass combination--is it more discriminating?

BACKGROUND: In 1987 Jass described a modified staging system for colorectal cancer using two anatomical criteria in common with the Dukes system; extent of spread through the bowel wall and the presence or absence of lymph node involvement. Additionally it used two 'biological' criteria; the nature of the expanding margin of the tumour (pushing or infiltrating), and the presence or absence of lymphocytic infiltration within the tumour. This study aims to determine whether a combination of the Dukes and Jass staging systems provides a better predictor of five year survival in patients with colorectal cancer than Dukes stage alone. METHOD: The Dukes and Jass stages along with vital status at five years were recorded for all 612 patients undergoing resection for colorectal cancer at the Royal Bolton Hospital and the Beaumont (BMI) Hospital, Bolton between 1991 and 1998. Kaplan-Meier survival curves with log rank test were used to show how survival correlated with Jass group stratified by Dukes stage. RESULTS: Both the Dukes B and the Dukes C tumours could be divided into groups with significantly different five year survival rates when stratified by Jass group. Five year survival for Dukes stage B, Jass group II tumours was 73.74% compared to Dukes B Jass III tumours whose survival was 51.38% (P = 0.0018). Five year survival for Dukes C Jass III tumours was 43.18% and for Dukes C Jass IV survival was 24.39% (P = 0.0029). CONCLUSION: By combining the biological criteria of the Jass staging system with the anatomically based Dukes system, both Dukes B and C tumours can be divided into groups with significantly different five year survival figures.

Protein kinase C alpha expression in normal breast, ductal carcinoma in situ and invasive ductal carcinoma.

The purpose of this study was to determine if Protein Kinase C alpha (PKC alpha) is altered in expression or localisation in normal breast, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). We obtained 14 mixed cases of invasive ductal carcinoma (IDC) and DCIS, 36 pure DCIS cases and 25 cases of normal breast. The sections were stained immunohistochemically for PKC alpha expression. Staining was cytoplasmic. The results showed a progressive reduction in staining intensity from normal breast to invasive ductal carcinoma. The staining pattern was heterogeneous in the cytoplasm of DCIS and IDC, but homogeneous in the cytoplasm of normal breast ductal epithelium. Interestingly, mitotic cells and cells with aberrant nuclear morphology showed increased cytoplasmic staining in DCIS and IDC. PKC alpha activity is altered in dividing or abnormal cells, but overall expression is reduced in IDC. This raises the possibility of an alteration in the subcellular localisation of PKC alpha which may relate to changes in desmosomal adhesive state.

Crude open biopsy rates for benign screen detected lesions no longer reflect breast screening quality--time to change the standard.

OBJECTIVES: To investigate the changing nature of the benign screen detected breast abnormalities removed at open biopsy over a seven year period and to compare this with the improving cancer detection rate and non-operative diagnosis rate. SETTING: The Bolton, Bury, and Rochdale Breast Screening Programme. METHODS: The histopathology reports of the benign lesions removed from patients undergoing open biopsy for screen detected abnormalities between 1 April 1994 and 31 March 2001 were reviewed and the lesions classified on the B1 to B5 scale. Cancer detection rates and non-operative cancer diagnosis rates were ascertained from the breast screening computer system. RESULTS: 148 benign surgical biopsies were performed in the seven year period. There was a moderate increase in the overall benign biopsy rate over the period (from 1.26 open biopsies per 1000 women screened for the three years 1994-97 to 1.63 open biopsies per 1000 women screened for the three years 1998-2001). The biopsy rate for B2 (benign) lesions decreased slightly over the study period but the biopsy rate for B3 lesions (that is, of uncertain malignant potential) more than doubled. The majority (84%) of the B3 lesions were radial scars. There was a steady improvement in the cancer detection rate and the non-operative cancer diagnosis rate over the period, similar to that seen nationally. CONCLUSIONS: Improvements in screening technique and detection ability result in an increase in the number of subtle radiologically indeterminate or suspicious lesions detected. Many of these are radial scars, which require excision. Crude benign open biopsy rates for screening programmes are no longer meaningful, and should now be refined with separate rates for B2 lesions and B3 lesions. High quality programmes can expect to have low B2 open biopsy rates and high B3 open biopsy rates. It is inappropriate to have an upper limit for the B3 open biopsy rate.

Life style characteristics associated with nutritional risk in elderly subjects aged 80-85 years.

A logistic regression model was applied to 627 elderly men and women, who participated in all three data collections of the SENECA study in 1989, 1993, and 1999, to test the hypothesis that nutritional status in 80-85 year old persons was related to functional and cognitive status, but not significantly affected by living arrangement. Additionally, the authors hypothesized that relationships between cognitive status and self-care ability, between self-care ability and living situation, and between cognitive status and living situation would be stronger with increasing age. Nutritional status was categorized as being well nourished (> or = 24) or at nutritional risk (<24) using the 18-item mini-nutritional assessment questionnaire (MNA). Diminished self-care ability was defined as inability to perform all 7 self-care items on the ADL instrument. Respondents were deemed to have possible cognitive impairment if they scored <24 on the MMSE test. Residence situation was categorized as either living alone, with spouse/partner, or with others. Nutritional risk was found to be associated with diminished cognitive status and diminished self-care ability, but not associated with living alone. Elderly people with diminished cognitive function and diminished self-care ability had a more than two times higher risk of being at nutritional risk. In addition, the strength of relationships between cognitive status and self-care ability, self-care ability and living situation, and cognitive ability and living situation all increased over time. In the oldest old lifestyle characteristics and functional ability appeared to be stronger predictors of risk for malnutrition than in younger adults.

Evidence of nerve sheath differentiation and high grade morphology in sclerosing epithelioid fibrosarcoma.

Sclerosing epithelioid fibrosarcoma is a recently described sarcoma in which ultrastructural evidence of fibroblastic differentiation forms part of the diagnostic criteria. This report describes a further case of this tumour, which showed evidence of both fibroblastic and perineurial differentiation by immunohistochemistry and electron microscopy, and which had areas of high grade morphology. The tumour metastasised and the patient died of disease 12 months after presentation. The relevance of these findings to diagnosis and differentiation in these tumours is discussed.

A study of breast cancers detected in the incident round of the UK NHS Breast Screening Programme: the importance of early detection and treatment of ductal carcinoma in situ.

One hundred and seventy eight cancers detected on incident round screening in the UK National Health Service Breast Screening Programme were reviewed. Critical review of the immediately preceding screening films (from 3 years previously) found abnormalities at the site of the subsequently detected cancer in 93 cases (52%). Forty-eight of these (27% of the total) had microcalcification as the sole abnormality. All of these 48 women had invasive ductal carcinoma and/or ductal carcinoma in situ (DCIS) (including four cases in which DCIS was associated with another type of primary invasive breast cancer). The finding of microcalcification on the previous mammograms at the site of a subsequently detected cancer was a strong predictor for the presence of DCIS (with or without associated invasive disease) (P<0.0001). Of the women with invasive ductal carcinoma, those with microcalcification on previous films were significantly more likely to have intermediate or high grade (grade 2 or 3) tumours than those women without microcalcification on previous films (P=0.0015). Previous films were also read blind by two independent experienced breast radiologists. Cancers were correctly identified by one or both readers in 39 cases. However, 35 of the remaining 139 cases showed microcalcification which was not detected or considered significant by the readers. If only these 139 'true negative' screens are analysed, similar associations are seen between microcalcification on previous films and subsequent finding of DCIS (P=0.03) and between microcalcification on previous films and high grade invasive ductal carcinomas (P=0.015). These findings provide support for the hypothesis that microcalcification seen on previous screening films at the site of a subsequently detected invasive ductal carcinoma represents ductal carcinoma in situ. In this series, 19 of 82 women (23%) with invasive ductal carcinoma in the 'true negative' screen group had microcalcification suggestive of DCIS on mammograms taken, on average, 3 years previously. Significant microcalcification is often overlooked using current detection criteria. Early detection and treatment of DCIS is essential in order to prevent the development of aggressive invasive disease. Revision of the NHSBSP targets for DCIS detection is recommended.

Induction of humoral and cellular responses in cynomolgus monkeys immunised with mannan-human MUC1 conjugates.

Mice immunised with oxidised mannan conjugated to the human mucin 1 (MUC1), produce MHC Class 1 restricted CD8+ cytotoxic T-cells which eradicate MUC1 + tumours, indicating potential for the immunotherapy of MUC1 + cancers in humans. We now describe preclinical studies performed in cynomolgus monkeys immunised with human or murine MUC1 conjugated to oxidised mannan, where immune responses and toxicity were examined. High titred antibodies specific for MUC1 were produced, MUC1 specific CD4+ and CD8+ T-cell proliferative responses and specific cytotoxic precursor cells (CTLp) were found, but not MUC1 specific cytotoxic T-cells (CTL). There was no toxicity and monkeys can be immunised against human MUC1 with mannan-MUC1 conjugates, but a humoral response (Th2 type) predominates. The results contrast with those obtained in mice when a CTL response (Th1 type) predominates.

The plasminogen activator inhibitor-2 gene is not required for normal murine development or survival.

Plasminogen activator inhibitor-2 (PAI-2), a member of the serpin gene family, is thought to serve as a primary regulator of plasminogen activation in the extravascular compartment. High levels of PAI-2 are found in keratinocytes, monocytes, and the human trophoblast, the latter suggesting a role in placental maintenance or embryo development. The primarily intracellular distribution of PAI-2 also may indicate a unique regulatory role in a protease-dependent cellular process such as apoptosis. To examine the potential functions of PAI-2 in vivo, we generated PAI-2-deficient mice by gene targeting in embryonic stem cells. Homozygous PAI-2-deficient mice exhibited normal development, survival, and fertility and were also indistinguishable from normal controls in response to a bacterial infectious challenge or endotoxin infusion. No differences in monocyte recruitment into the peritoneum were observed after thioglycollate injection. Epidermal wound healing was equivalent among PAI-2 -/- null and control mice. Finally, crossing PAI-2 -/- with PAI-1 -/- mice to generate animals deficient in both plasminogen activator inhibitors failed to uncover an overlap in function between these two related proteins.

Differentiating cells of murine stratified squamous epithelia constitutively express plasminogen activator inhibitor type 2 (PAI-2).

In stratified squamous epithelia a critical balance among cell proliferation, differentiation, and death must be maintained in order for these tissues to fulfill their barrier function. Previous studies have demonstrated that plasminogen activator inhibitor 2 (PAI-2) is a product of differentiating epidermal keratinocytes, suggesting a role for this inhibitor during squamous differentiation. Furthermore, in certain tumor cell lines, overexpression of PAI-2 confers resistance to the induction of programmed cell death, suggesting cytoprotective function(s). In the present study we demonstrate that PAI-2 mRNA and protein are constitutively and uniquely expressed in differentiating cells of murine stratified squamous epithelia, including epidermis, esophagus, vagina, oral mucosa, and tongue. PAI-2 immunohistochemical localization patterns suggest a predominantly cytosolic distribution, consistent with biochemical identification of the major PAI-2 species as a 43-kDa, presumably non-glycosylated protein. Functional analysis shows that the majority of epithelial PAI-2 is active. In contrast to the high levels of PAI-2 expression in stratified squamous epithelia, little or no PAI-2 is detectable in simple epithelia. These findings suggest that epithelial PAI-2 may mediate inhibition of intracellular proteinases associated with events during terminal differentiation and death that are unique to stratified squamous epithelia.

Living alone does not adversely affect nutrient intake and nutritional status of 70- to 75-year-old men and women in small towns across Europe.

This study determined the relationships between living alone and a variety of sociodemographic variables and dietary intake and nutritional status of 70- to 75-year-old men and women across Europe. Data from nine centers, collected as part of the SENECA study, were selected for analysis. Respondents were categorized as either living alone, living with a spouse/partner only, or living with a spouse/partner and/or other person(s). Analyses included chi-square statistics, t-tests, and analysis of variance, measures of relationships and differences between residential-status groups. The sample included 512 subjects who lived alone, 1017 who lived with a spouse/partner only, and 380 who lived with a spouse/partner and/or other person(s). Variables which differed significantly by living arrangement included higher vitamin A, calcium, riboflavin and water intake by both males and females living alone as compared to either those living with a spouse, those living with others, or both groups. Females who lived alone had lower energy intake than those who lived with other than a spouse/partner, and women who lived alone or as couples versus those who lived with others had lower protein and carbohydrate intakes. Males who lived alone had significantly lower intakes of vitamin C than those who lived with person(s) other than a spouse, but still they were considerably above recommended levels. Respondents who lived with a spouse/partner only were less likely to have an unfavorable BMI status than people in the other two groups. Thus, nutrient intakes of 70- to 75-year-olds across Europe are generally not adversely impacted by living alone, and relative to some nutrients, namely vitamin A, calcium, and riboflavin, their diets are better than those living in one or both of the other residential categories.