Repeated large-scale retreat and advance of Totten Glacier indicated by inland bed erosion.

Climate variations cause ice sheets to retreat and advance, raising or lowering sea level by metres to decametres. The basic relationship is unambiguous, but the timing, magnitude and sources of sea-level change remain unclear; in particular, the contribution of the East Antarctic Ice Sheet (EAIS) is ill defined, restricting our appreciation of potential future change. Several lines of evidence suggest possible collapse of the Totten Glacier into interior basins during past warm periods, most notably the Pliocene epoch, causing several metres of sea-level rise. However, the structure and long-term evolution of the ice sheet in this region have been understood insufficiently to constrain past ice-sheet extents. Here we show that deep ice-sheet erosion-enough to expose basement rocks-has occurred in two regions: the head of the Totten Glacier, within 150 kilometres of today's grounding line; and deep within the Sabrina Subglacial Basin, 350-550 kilometres from this grounding line. Our results, based on ICECAP aerogeophysical data, demarcate the marginal zones of two distinct quasi-stable EAIS configurations, corresponding to the 'modern-scale' ice sheet (with a marginal zone near the present ice-sheet margin) and the retreated ice sheet (with the marginal zone located far inland). The transitional region of 200-250 kilometres in width is less eroded, suggesting shorter-lived exposure to eroding conditions during repeated retreat-advance events, which are probably driven by ocean-forced instabilities. Representative ice-sheet models indicate that the global sea-level increase resulting from retreat in this sector can be up to 0.9 metres in the modern-scale configuration, and exceeds 2 metres in the retreated configuration.

Pathological pelvic fracture following long-term bisphosphonate use in a 63-year-old woman.

A 63-year-old woman presented with a low energy pelvic fracture, which showed no signs of healing. Initial fractures were to the right hemipelvis, later followed by a right fractured neck of femur. We present a complicated patient journey, management dilemmas and highlight the growing concern with long-term bisphosphonate treatment.

An in vitro study of alginate oligomer therapies on oral biofilms.

OBJECTIVES: The in vitro effect of a novel, oligosaccharide nanomedicine OligoG against oral pathogen-related biofilms, both alone and in the presence of the conventional anti-bacterial agent triclosan, was evaluated. METHODS: The effect of OligoG±triclosan was assessed against established Streptococcus mutans and Porphyromonas gingivalis biofilms by bacterial counts and image analysis using LIVE/DEAD(®) staining and atomic force microscopy (AFM). The effect of triclosan and OligoG surface pre-treatments on bacterial attachment to titanium and polymethylmethacrylate was also studied. RESULTS: OligoG potentiated the antimicrobial effect of triclosan, particularly when used in combination at 0.3% against S. mutans grown in artificial saliva. OligoG was less effective against established P. gingivalis biofilms. However, attachment of P. gingivalis, to titanium in particular, was significantly reduced after surface pre-treatment with OligoG and triclosan at 0.01% when compared to controls. Light microscopy and AFM showed that OligoG was biocidal to P. gingivalis, but not S. mutans. CONCLUSIONS: OligoG and triclosan when used in combination produced an enhanced antimicrobial effect against two important oral pathogens and reduced bacterial attachment to dental materials such as titanium, even at reduced triclosan concentrations. Whilst the use of triclosan against oral bacteria has been widely documented, its synergistic use with OligoG described here, has not previously been reported. The use of lower concentrations of triclosan, if used in combination therapy with OligoG, could have environmental benefits. CLINICAL IMPORTANCE: The potentiation of antimicrobial agents by naturally occurring oligomers such as OligoG may represent a novel, safe adjunct to conventional oral hygiene and periodontal therapy. The ability of OligoG to inhibit the growth and impair bacterial adherence highlights its potential in the management of peri-implantitis.

A novel ex vivo culture model for inflammatory bone destruction.

Pathological alterations in the balance of bone metabolism are central to the progression of inflammatory bone diseases such as periodontal disease. We have developed and characterized a novel ex vivo murine mandible model of inflammatory bone destruction. Slices of mandible were cultured for 14 days in the presence or absence of P. gingivalis lipopolysaccharide (LPS) or pro-inflammatory cytokines. Following culture, cell viability and tissue histomorphometry were assessed with quantification of matrix proteins, resident osteoclasts, ligament cells, monocytes, macrophages, and neutrophils. In the absence of inflammatory factors, culture viability, osteoclasts, and matrix components were maintained. LPS or TNFα stimulation demonstrated an increase in cellular proliferation, monocyte cells, osteoclast differentiation, and matrix degradation. Pathophysiological bone metabolism can be induced via exposure to LPS and direct influence of TNFα within the model despite the absence of systemic circulation, providing a model for inflammatory bone destruction and investigation of the effects of novel therapeutics.

Locked intramedullary nailing of symptomatic metastases in the humerus.

The humerus is a common site for skeletal metastases in the adult. Surgical stabilisation of such lesions is often necessary to relieve pain and restore function. These procedures are essentially palliative and should therefore provide effective relief from pain for the remainder of the patient's life without the need for further surgical intervention. We report a retrospective analysis of 35 patients (37 nails) with symptomatic metastases in the shaft of the humerus which were treated by locked, antegrade nailing. There were 27 true fractures (73.0%) and ten painful deposits (27.0%). Relief from pain was excellent in four (11.4%), good in 29 (82.9%) and fair in two (5.7%) on discharge. Function was improved in all but one patient. One case of palsy of the radial nerve was noted. The mean postoperative survival was 7.1 months (0.2 to 45.5) which emphasises the poor prognosis in this group of patients. There were no failures of fixation and no case in which further surgery was required. Antegrade intramedullary nailing is an effective means of stabilising the humerus for the palliative treatment of metastases. It relieves pain and restores function to the upper limb with low attendant morbidity.

Subjective memory complaints and awareness of memory functioning in mild cognitive impairment: a systematic review.

OBJECTIVES: Subjective memory complaint (SMC) is central to the diagnosis of mild cognitive impairment (MCI). People with MCI are at a higher risk of progressing to dementia, and research on SMC is contradictory in terms of the accuracy of SMC and its predictive role for future dementia. One possible reason for these contradictory findings is that the level of awareness of memory function may vary among people with MCI. This review examines whether the level of awareness of memory functioning varies amongst people classified as having MCI and whether there is support for the suggestion that the level of awareness in MCI predicts future progression to dementia. METHOD: Sixteen studies were identified which evaluate the awareness level in people classified as having MCI in either a clinical or research setting. In addition to the outcome of each study, the conceptualization of awareness, 'object' of awareness and methodology were also considered. RESULTS: There is evidence to show that the level of awareness in MCI does vary, and this may have implications for future progression to dementia. CONCLUSIONS: Given the increased risk of progression to dementia for those identified as having MCI, the role of awareness should be explored further with due consideration given to the conceptualization of awareness and the methodology employed. The finding of variability in awareness has implications for the use of SMC in the diagnostic criteria for MCI.

Competition between immune function and lipid transport for the protein apolipophorin III leads to stress-induced immunosuppression in crickets.

Intense physical activity results in transient immunosuppression in a wide range of animals. We tested the hypothesis that competition between immune function and lipid transport for the protein apolipophorin III (apoLpIII) can cause transient immunosuppression in crickets. Both flying, an energetically demanding behavior, and an immune challenge reduced the amount of monomeric (free) apoLpIII in the hemolymph of crickets. Because both immune function and flying depleted free apoLpIII, these two phenomena could be in competition for this protein. We showed that immune function was sensitive to the amount of free apoLpIII in the hemolymph. Reducing the amount of free apoLpIII in the hemolymph using adipokinetic hormone produced immunosuppression. Increasing apoLpIII levels after flight by pre-loading animals with trehalose reduced immunosuppression. Increasing post-flight apoLpIII levels by injecting purified apoLpIII also reduced flight-induced immunosuppression. These results show that competition between lipid transport and immune function for the same protein can produce transient immunosuppression after flight-or-fight behavior. Intertwined physiological systems can produce unexpected trade-offs.

A case of 46,X,der(X)t(X;X)(q22.1;p11) Xq22.1-->Xqter in a 12-year-old girl with premature ovarian failure.

Premature ovarian failure due to Xp duplication and Xq deletion has been reported in four patients, the youngest of whom was 18 years old. The diagnosis has been made with new techniques for genetic analysis, such as comparative genomic hybridization and fluorescence in situ hybridization. We report the youngest case (a 12-year-old who presented with irregular menses), of premature ovarian failure due to Xp duplication and Xq deletion and the first with 46,X,der(X)t(X;X)(q22.1;p11). The diagnosis was made using C-banding and fluorescent in situ hybridization with locus-specific probes. This case highlights the need to use advanced genetic strategies to determine karyotypic and phenotypic abnormalities.

Supratentorial epidural hematoma of traumatic etiology in infants.

INTRODUCTION AND BACKGROUND: Traumatic epidural hematoma (EDH) represents a rare head injury complication in infants. Its diagnosis can be quite challenging because its clinical presentation is usually subtle and nonspecific. In our current communication, we present our data regarding the presentation of infants with EDH, their management, and their long-term outcome. MATERIALS AND METHODS: In a retrospective study, the hospital and outpatient clinic charts and imaging studies (head CT and skull X-rays) of 31 infants with pure, supratentorial EDH of traumatic origin were meticulously reviewed. Children Coma Scale score and Trauma Infant Neurologic Score (TINS) were also reviewed. The most common presenting symptom was irritability, which occurred in 18/31 (58.1%) of our patients. Pallor (in 30/31 patients) and cephalhematoma (in 21/31 patients) were the most commonly occurring clinical signs upon admission; both signs represent signs of significant clinical importance. Surgical evacuation via a craniotomy was required in 24/31 of our patients, while 7/31 patients were managed conservatively. The mortality rate in our series was 6.5% (2/31 patients), and our long-term morbidity rate was 3.2% (1/31 patients). CONCLUSIONS: EDH in infants represents a life-threatening complication of head injury, which requires early identification and prompt surgical or conservative management depending on the patient's clinical condition, size of EDH, and presence of midline structure shift on head CT scan. Mortality and long-term morbidity are low with early diagnosis and prompt treatment.

Electron temperature of ultracold plasmas.

We study the evolution of ultracold plasmas by measuring the electron temperature. Shortly after plasma formation, competition between heating and cooling mechanisms drives the electron temperature to a value within a narrow range regardless of the initial energy imparted to the electrons. In agreement with theory predictions, plasmas exhibit values of the Coulomb coupling parameter Gamma less than 1.

A prospective randomized comparison of extensive prostate biopsy to standard biopsy with assessment of diagnostic yield, biopsy pain and morbidity.

In a prospective randomized study, we compare standard prostate biopsy to extensive biopsy utilizing intravenous conscious sedation (IVCS). Initial biopsy patients (n=197) were randomized to either standard biopsy using intrarectal lidocaine gel (6-12 biopsies, mean 10.1) or extensive biopsy (24 biopsies) using IVCS. Cancer detection and urinary symptoms were no different between groups. However, biopsy pain was rated significantly lower and satisfaction significantly higher in the extensive biopsy group. Temporary urinary retention occurred in 4% of the extensive biopsy group. Extended biopsy with 24 samples does not improve cancer detection compared to standard biopsy when 10 cores are obtained. Extensive biopsy is very well tolerated and associated with less pain and more satisfaction than standard biopsy.

Novel roles of neuropeptide processing enzymes: EC3.4.24.15 in the neurome.

Neuropeptide processing metalloenzymes, such as angiotensin converting enzyme, neprilysin, endothelin converting enzyme, neurolysin, and EC3.4.24.15 (EP24.15), are central to the formation and degradation of bioactive peptides. We present EP24.15 as a paradigm for novel functions ascribed to these enzymes in the neurome. Although the neurome typically encompasses proteomes of the brain and central nervous system, exciting new roles of these neuropeptidases have been demonstrated in other organ systems. We discuss the involvement of EP24.15 with clinical sequelae involving the use of gonadotropin-releasing hormone (GnRH; LHRH) analogs that act as enzyme inhibitors, in vascular physiology (blood pressure regulation), and in the hematologic system (immune surveillance). Hemodynamic forces, such as cyclic strain and shear stress, on vascular cells, induce an increase in EP24.15 transcription, suggesting that neuropeptidase-mediated hydrolysis of pressor/depressor peptides is likely regulated by changes in hemodynamic force and blood pressure. Lastly, EP24.15 regulates surface expression of major histocompatibility complex Class I proteins in vivo, suggesting that EP24.15 may play an important role in maintenance of immune privilege in sites of increased endogenous expression. In these extraneural systems, regulation of both neuropeptide and other peptide substrates by neuropeptidases indicates that the influence of these enzymes may be more global than was anticipated previously, and suggests that their attributed role as neuropeptidases underestimates their physiologic actions in the neural system.

Long-term effects of the mammary carcinogen 7,12-dimethylbenz(a) anthracene on hypothalamic gonadotropin-releasing hormone and its pituitary receptor gene expression, during the promotion stage, in female Sprague-Dawley rats.

A single intragastric administration of 7,12-dimethylbenz(a)anthracene (DMBA) has been shown to induce mammary tumors in young cycling female Sprague-Dawley rats. The appearance of these tumors is preceded by a series of neuroendocrine disturbances, including attenuation of the preovulatory luteinizing hormone (LH) surge and amplification of the preovulatory 17beta-estradiol surge, and gonadotropin-releasing hormone (GnRH) released in vitro. In this study, we examined the hypothesis that DMBA administration decreases levels of GnRH mRNA in the preoptic area-anterior hypothalamus (POA-AH) and GnRH receptor (GnRH Rc) mRNA and protein in the anterior pituitary gland. Sprague-Dawley rats, 55-60 days of age with regular estrous cycles, received a single dose of 15 mg DMBA in 1 ml sesame oil delivered by intragastric intubation. A first series of experiments was performed for the measurement of hypothalamic GnRH mRNA and pituitary GnRH Rc mRNA levels. A second series of experiments was performed for the measurement of pituitary GnRH receptor. In both experiments, animals were sacrificed by decapitation at 11.00, 16.00, 18.00 and 20.00 h on each day of the 7th or 8th estrous cycle (28-32 days) after treatment. GnRH and GnRH receptor mRNAs were quantified using solution hybridization-RNase protection assay. The GnRH Rc was quantified using the 125I-D-Ala6-N-Met-Leu6-des-Gly10-ethylamide GnRH. DMBA-treatment produced no significant effect on the overall mean values of GnRH mRNA. GnRH mRNA levels in control rats rose significantly between 16.00 and 20.00 h on proestrus and between 18.00 and 20.00 h on diestrus I. DMBA-treated rats had a surge in GnRH mRNA levels at 18.00 h on proestrus, and showed additional surges at 18.00h on diestrus II and estrus. GnRH receptor mRNA content in the anterior pituitary gland surged at 16.00h on certain days of the cycle in both groups of rats. In control rats, only the surge on diestrus II proved significant, whereas DMBA-treated rats exhibited significant surges on diestrus I, diestrus II and proestrus. GnRH receptor mRNA values were significantly lower on both days of diestrus in DMBA-treated rats compared with controls. GnRH Rc peptide content, like GnRH receptor in RNA surged at 16.00h in both groups with the exception of a marked fall on proestrus day for DMBA treated rats. A reduction in the amplitude of the surge was also seen on the day of estrous and to a lesser extend on the day of diestrus DII in DMBA treated animal. Overall, there was a disruption of the GnRH Rc pattern which culminate on the day of proestrus in DMBA-treated animals. Interestingly, the daily rise between 11.00 and 16.00h which is the more pronounced on the day of proestrus in control animals, was completely blunted in DMBA-treated rats. Overall, the results are consistent with the hypothesis that the carcinogen attenuates, directly or indirectly, preovulatory biosynthesis of the GnRH receptor and LH release. Obviously, the changes in GnRH might occur simultaneously, independently from mammary tumorigenesis, but may play a role, in association with others DMBA-induced neuroendocrine disorders, in the promotion stage of mammary tumors in the Sprague-Dawley female rat.

Unexpected effects of FERM domain mutations on catalytic activity of Jak3: structural implication for Janus kinases.

Janus kinases comprise carboxyterminal kinase, pseudokinase, SH2-like, and N-terminal FERM domains. We identified three patient-derived mutations in the FERM domain of Jak3 and investigated the functional consequences of these mutations. These mutations inhibited receptor binding and also abrogated kinase activity, suggesting interactions between the FERM and kinase domains. In fact, the domains were found to physically associate, and coexpression of the FERM domain enhanced activity of the isolated kinase domain. Conversely, staurosporine, which alters kinase domain structure, disrupted receptor binding, even though the catalytic activity of Jak3 is dispensable for receptor binding. Thus, the Jak FERM domain appears to have two critical functions: receptor interaction and maintenance of kinase integrity.

Relationship between obesity and race in predicting adverse pathologic variables in patients undergoing radical prostatectomy.

OBJECTIVES: To determine whether obesity is associated with more advanced prostate cancer (PCa) in radical prostatectomy patients and to explore the ethnic variability in body mass index (BMI) as a potential explanation for racial differences in PCa risk. METHODS: A multi-institutional retrospective analysis of the clinical and pathologic parameters was performed on data from 860 patients with PCa undergoing radical prostatectomy between 1992 and 1998. Patient height and weight was used to calculate the BMI, which categorized patients into obese (BMI 30 kg/m(2) or greater), overweight (BMI 25 to 30 kg/m(2)), and normal (BMI 25 kg/m(2) or less) groups. Age, serum prostate-specific antigen level, pathologic stage, and Gleason score for each group were compared. The distribution of the BMI in each of four ethnic groups was also determined. RESULTS: Of 860 patients, 171 (20%) were obese, 425 (49%) overweight, and 264 (31%) normal. The obese patients presented at a younger mean age (62 years, P = 0.001), had higher mean Gleason scores (6.7, P = 0.002), had a higher likelihood of Gleason score 7 or greater cancer (71%, P = 0.003), and had a lower chance of organ-confined cancer (46%, P = 0.050). The BMI was highest in blacks, followed by whites and Asians, and blacks had significantly higher grade cancers (P = 0.045). In multiple logistic regression analysis of the BMI and race, only BMI remained an independent predictor of Gleason grade. CONCLUSIONS: Obese patients with PCa present for radical prostatectomy at a younger age with higher grade and more pathologically advanced cancers. Blacks have higher grade cancers than other ethnic groups and, at the same time, have significantly higher BMIs. These findings suggest that obesity may in part account for the racial variability in PCa risk.

Presence of luteinizing hormone-releasing hormone fragments in the rhesus monkey forebrain.

Previously, we have shown that two types of luteinizing hormone-releasing hormone (LHRH) -like neurons, "early" and "late" cells, were discernible in the forebrain of rhesus monkey fetuses by using antiserum GF-6, which cross-reacts with several forms of LHRH. The "late" cells that arose from the olfactory placode of monkey fetuses at embryonic days (E) 32-E36, are bona fide LHRH neurons. The "early" cells were found in the forebrain at E32-E34 and settled in the extrahypothalamic area. The molecular form of LHRH in "early" cells differs from "late" cells, because "early" cells were not immunopositive with any specific antisera against known forms of LHRH. In this study, we investigated the molecular form of LHRH in the "early" cells in the nasal regions and brains of 13 monkey fetuses at E35 to E78. In situ hybridization studies suggested that both "early" and "late" LHRH cells expressed mammalian LHRH mRNA. Furthermore, "early" cells predominantly contain LHRH1-5-like peptide and its cleavage enzyme, metalloendopeptidase E.C.3.4.24.15 (EP24.15), which cleaves LHRH at the Tyr5-Gly6 position. This conclusion was based on immunocytochemical labeling with various antisera, including those against LHRH1-5, LHRH4-10, or EP24.15, and on preabsorption tests. Therefore, in primates, a group of neurons containing mammalian LHRH mRNA arises at an early embryonic stage before the migration of bona fide LHRH neurons, and is ultimately distributed in the extrahypothalamic region. These extrahypothalamic neurons contain LHRH fragments, rather than fully mature mammalian LHRH. The origin and function of these neurons remain to be determined.

Repeat biopsy strategy in patients with atypical small acinar proliferation or high grade prostatic intraepithelial neoplasia on initial prostate needle biopsy.

PURPOSE: Isolated high grade prostatic intraepithelial neoplasia and/or atypical small acinar proliferation on prostate biopsy increases the risk of identifying cancer on repeat biopsy. We report the results of repeat prostate biopsy for high grade prostatic intraepithelial neoplasia and/or atypical small acinar proliferation, and propose an optimal repeat biopsy strategy. MATERIALS AND METHODS: Of 1,391 men who underwent standard systematic sextant biopsy of the prostate 137 (9.8%) had isolated high grade prostatic intraepithelial neoplasia or atypical small acinar proliferation, including 100 who underwent repeat prostate biopsy within 12 months of the initial biopsy. RESULTS: Adenocarcinoma was detected in 47 of the 100 patients who underwent repeat biopsy. The initial biopsy site of high grade prostatic intraepithelial neoplasia and/or atypical small acinar proliferation matched the sextant location of cancer on repeat biopsy in 22 cases (47%). Repeat biopsy directed only to the high grade prostatic intraepithelial neoplasia and/or atypical small acinar proliferation site on initial biopsy would have missed 53% of cancer cases. In 12 of the 47 men (26%) cancer was limited to the side of the prostate contralateral to the side of high grade prostatic intraepithelial neoplasia and/or atypical small acinar proliferation. Of the 31 patients with cancer in whom the transition zone was sampled cancer was limited to the transition zone in 4 (13%) and evident at other biopsy sites in 13 (42%). The only significant predictor of positive repeat biopsy was mean prostate specific antigen velocity plus or minus standard error (1.37 +/- 1.4 versus 0.52 +/- 0.8 ng./ml. per year, p <0.001). CONCLUSIONS: Patients with isolated high grade prostatic intraepithelial neoplasia and/or atypical small acinar proliferation on prostate biopsy are at 47% risk for cancer on repeat biopsy. The optimal repeat biopsy strategy in this setting should include bilateral biopsies of the standard sextant locations. We also strongly recommend that transition zone sampling should be considered.

Dynamics of collapsing and exploding Bose-Einstein condensates.

When atoms in a gas are cooled to extremely low temperatures, they will-under the appropriate conditions-condense into a single quantum-mechanical state known as a Bose-Einstein condensate. In such systems, quantum-mechanical behaviour is evident on a macroscopic scale. Here we explore the dynamics of how a Bose-Einstein condensate collapses and subsequently explodes when the balance of forces governing its size and shape is suddenly altered. A condensate's equilibrium size and shape is strongly affected by the interatomic interactions. Our ability to induce a collapse by switching the interactions from repulsive to attractive by tuning an externally applied magnetic field yields detailed information on the violent collapse process. We observe anisotropic atom bursts that explode from the condensate, atoms leaving the condensate in undetected forms, spikes appearing in the condensate wavefunction and oscillating remnant condensates that survive the collapse. All these processes have curious dependences on time, on the strength of the interaction and on the number of condensate atoms. Although the system would seem to be simple and well characterized, our measurements reveal many phenomena that challenge theoretical models.

Australia's campaign to eradicate bovine tuberculosis: the battle for freedom and beyond.

In 1970, voluntary State-based TB control programs in Australia were replaced by a coordinated national campaign to eliminate both brucellosis and tuberculosis from the cattle population. The campaign was funded and managed under tripartite agreement by State/Territory and Commonwealth governments and Industry. The tuberculosis component of the campaign relied on test and slaughter with surveillance for the disease in abattoirs and trace-back to property of origin an essential component. Because of the moderate sensitivity of the skin test ( approximately 70%), testing was repeated at prescribed intervals over a number of years. In the more hostile environment of northern Australia, novel strategies were developed to maximize musters and remove 'at risk' animals. Australia is fortunate it did not have a feral host for M. bovis (apart from buffalo, which were included in the campaign) to complicate eradication. A national granuloma submission program was implemented in 1992 to increase the intensity of abattoir monitoring. Selective or total depopulation was used in some herds to achieve the requirements of the national Standard Definitions and Rules of the Campaign and achieve the status of 'TB Free Area' in December 1997. Monitoring for tuberculosis has continued under the 5-year Tuberculosis Freedom Assurance Program and measures to further reduce the risk of new cases have been implemented.