Transient Radio Signatures from Neutron Star Encounters with QCD Axion Miniclusters.

The QCD axion is expected to form dense structures known as axion miniclusters if the Peccei-Quinn symmetry is broken after inflation. Miniclusters that have survived until today will interact with neutron stars (NSs) in the Milky Way to produce transient radio signals from axion-photon conversion in the NS magnetosphere. We quantify the properties of these encounters and find that they occur frequently [O(1-100)day^{-1}], last between a day and a few months, are spatially clustered toward the Galactic Center, and can reach observable fluxes. These radio transients are within reach of current generation telescopes and therefore offer a promising pathway to discovering QCD axion dark matter.

Unique Multimessenger Signal of QCD Axion Dark Matter.

We propose a multimessenger probe of QCD axion dark matter based on observations of black hole-neutron star binary inspirals. It is suggested that a dense dark matter spike may grow around intermediate mass black holes (10^{3}-10^{5} M_{⊙}). The presence of such a spike produces two unique effects: a distinct phase shift in the gravitational wave strain during the inspiral and an enhancement of the radio emission due to the resonant axion-photon conversion occurring in the neutron star magnetosphere throughout the inspiral and merger. Remarkably, the observation of the gravitational wave signal can be used to infer the dark matter density and, consequently, to predict the radio emission. We study the projected reach of the LISA interferometer and next-generation radio telescopes such as the Square Kilometre Array. Given a sufficiently nearby system, such observations will potentially allow for the detection of QCD axion dark matter in the mass range 10^{-7} eV to 10^{-5} eV.

An ultra-sensitive aptasensor on optical fibre for the direct detection of bisphenol A.

We present a plasmonic biosensor capable of detecting the presence of bisphenol A in ultra-low concentrations, yielding a wavelength shift of 0.15 ±â€¯0.01 nm in response to a solution of 1 fM concentration with limit of detection of 330 ±â€¯70 aM The biosensing device consists of an array of gold nano-antennae with a total length of 2.3 cm that generate coupled localised surface plasmons (cLSPs) and is covalently modified with an aptamer specific for bisphenol A recognition. The array of nano-antennae is fabricated on a lapped section of standard telecommunication optical fibre, allowing for potential multiplexing and its use in remote sensing applications. These results have been achieved without the use of enhancement techniques and therefore the approach allows the direct detection of bisphenol A, a low molecular weight (228 Da) target usually detectable only by indirect detection strategies. Its detection at such levels is a significant step forward in measuring small molecules at ultra-low concentrations. Furthermore, this new sensing platform paves the way for the development of portable systems for in-situ agricultural measurements capable of retrieving data on a substance of very high concern at ultra-low concentrations.

Assessing Near-Future Direct Dark Matter Searches with Benchmark-Free Forecasting.

Forecasting the signal discrimination power of dark matter (DM) searches is commonly limited to a set of arbitrary benchmark points. We introduce new methods for benchmark-free forecasting that instead allow an exhaustive exploration and visualization of the phenomenological distinctiveness of DM models, based on standard hypothesis testing. Using this method, we reassess the signal discrimination power of future liquid xenon and argon direct DM searches. We quantify the parameter regions where various nonrelativistic effective operators, millicharged DM, and magnetic dipole DM can be discriminated, and where upper limits on the DM mass can be found. We find that including an argon target substantially improves the prospects for reconstructing the DM properties. We also show that only in a small region with DM masses in the range 20-100 GeV and DM-nucleon cross sections a factor of a few below current bounds can near-future xenon and argon detectors discriminate both the DM-nucleon interaction and the DM mass simultaneously. In all other regions only one or the other can be obtained.

Effects of pericardiectomy on training- and myocardial infarction-induced left ventricular hypertrophy, chamber dimensions and gene expression.

The primary purpose of the study was to evaluate whether a pericardiectomy (PERI) alters training- or myocardial infarction (MI)-induced left ventricular hypertrophy (LVH), chamber geometry, gene expression and/or running performance. Mice were randomized into 6 groups: naïve control (CONT)-sedentary (Sed), CONT-trained (Tr), PERI-Sed, PERI-Tr, MI-Sed and MI-Tr. MI mice also received a pericardiectomy as part of the MI surgical procedure. 10 weeks of treadmill running resulted in enhanced running performance-to-exhaustion in all 3 trained groups (CONT-Tr, PERI-Tr, MI-Tr) compared to sedentary cohorts (P<0.001). Training also resulted in similar increases in normalized LVH (LV/BW) in CONT-Tr and PERI-Tr mice. 2D-echocardiographic evaluation of LV internal chamber dimensions revealed that stroke diameter (SD) was larger in PERI compared to MI (P<0.01) but not CONT mice. Ventricular B-type natriuretic peptide mRNA (BNP) was elevated only in the 2 MI groups. Left ventricle ß1-adrenergic receptor (ß1-AR) and melusin transcripts both demonstrated an overall increase in trained compared to sedentary mice (both P<0.05). Additionally long-term pericardiectomy did not further enhance running performance or increase LV/BW in either sedentary or trained mice.

Regulation of osteosarcoma cell lung metastasis by the c-Fos/AP-1 target FGFR1.

Osteosarcoma is the most common primary malignancy of the skeleton and is prevalent in children and adolescents. Survival rates are poor and have remained stagnant owing to chemoresistance and the high propensity to form lung metastases. In this study, we used in vivo transgenic models of c-fos oncogene-induced osteosarcoma and chondrosarcoma in addition to c-Fos-inducible systems in vitro to investigate downstream signalling pathways that regulate osteosarcoma growth and metastasis. Fgfr1 (fibroblast growth factor receptor 1) was identified as a novel c-Fos/activator protein-1(AP-1)-regulated gene. Induction of c-Fos in vitro in osteoblasts and chondroblasts caused an increase in Fgfr1 RNA and FGFR1 protein expression levels that resulted in increased and sustained activation of mitogen-activated protein kinases (MAPKs), morphological transformation and increased anchorage-independent growth in response to FGF2 ligand treatment. High levels of FGFR1 protein and activated pFRS2α signalling were observed in murine and human osteosarcomas. Pharmacological inhibition of FGFR1 signalling blocked MAPK activation and colony growth of osteosarcoma cells in vitro. Orthotopic injection in vivo of FGFR1-silenced osteosarcoma cells caused a marked twofold to fivefold decrease in spontaneous lung metastases. Similarly, inhibition of FGFR signalling in vivo with the small-molecule inhibitor AZD4547 markedly reduced the number and size of metastatic nodules. Thus deregulated FGFR signalling has an important role in osteoblast transformation and osteosarcoma formation and regulates the development of lung metastases. Our findings support the development of anti-FGFR inhibitors as potential antimetastatic therapy.

The demise of bloodletting.

Bloodletting was a practice favoured by doctors and barber-surgeons for many centuries, and is now, perhaps surprisingly, still employed for a few specific indications. The effectiveness of bloodletting for treating diseases such as pneumonia was convincingly challenged in the mid-nineteenth century, but medical conservatism ensured the practice continued well into the twentieth century. As late as 1942, a famous medical textbook considered bloodletting appropriate treatment for pneumonia.

Investigating the function of Ddr48p in Candida albicans.

Candidiasis now represents the fourth most frequent nosocomial infection both in the United States and worldwide. Candida albicans is an increasingly common threat to human health as a consequence of AIDS, steroid therapy, organ and tissue transplantation, cancer therapy, broad-spectrum antibiotics, and other immune defects. The pathogenic potential of C. albicans is intimately related to certain key processes, including biofilm formation and filamentation. Ddr48p is a damage response protein that is significantly upregulated during both biofilm formation and filamentation, but its actual function is unknown. Previous studies have indicated that this protein may be essential in C. albicans but not Saccharomyces cerevisiae. Here we examined the function of Ddr48p and investigated the role of this protein in biofilm formation and filamentation. We demonstrated that this protein is not essential in C. albicans and appears to be dispensable for filamentation. However, DDR48 is required for the flocculation response stimulated by 3-aminotriazole-induced amino acid starvation. Furthermore, we examined the response of this deletion strain to a wide variety of environmental stressors and antifungal compounds. We observed several mild sensitivity or resistance phenotypes and also found that Ddr48p contributes to the DNA damage response of C. albicans. The results of this study reveal that the role of this highly expressed protein goes beyond a general stress response and impinges on a key facet of pathogenesis, namely, the ability to sense and respond to changes in the host environment.

Inhibition of NADPH oxidase alleviates experimental diabetes-induced myocardial contractile dysfunction.

AIM: O(2) (-) production is implicated in cardiac dysfunction for a number of diseases including diabetes. Activation of the O(2) (-)-producing enzyme NADPH oxidase is seen in diabetes, although its role in diabetic cardiomyopathy is unclear. This study was designed to evaluate the effect of NADPH oxidase inhibition on cardiac function in diabetes. METHODS: Experimental diabetes was induced in adult C57 mice using streptozotocin (STZ, 150 mg/kg, i.p.) prior to the administration of the NADPH oxidase inhibitor apocynin (4 mg/kg/day) for 2 weeks. Left ventricular (LV) and myocyte contractile functions were evaluated using echocardiography and edge-detection, respectively. RESULTS: STZ elicited hyperglycaemia and reduced body weight gain, which was unaffected by apocynin. STZ significantly reduced fractional shortening, LV wall thickness, peak shortening, maximal velocity and duration of shortening or relengthening, the effects of which - with the exception of wall thickness - were significantly attenuated or ablated by apocynin. Western blot analysis revealed that the effects of comparable Akt phosphorylation, reduced AMPK phosphorylation, downregulation of sarco(endo)plasmic reticulum Ca(2+)-ATPase and lessened phosphorylation of phospholamban in diabetic myocardium were unaffected by apocynin. Both apocynin and the nitric oxide synthase (NOS) inhibitor l-arginine methyl ester (L-NAME) inhibited elevated O(2) (-) production in diabetes without any additive effect between the two, indicating the presence of endothelial nitric oxide synthase (eNOS) uncoupling. However, neither diabetes nor apocynin altered the expression of heat shock protein 90 and eNOS phosphorylation (Ser(1177)). In addition, apocynin mitigated elevated levels of nitrotyrosine and nitric oxide in diabetes. CONCLUSION: Taken together, these data indicate the beneficial role of NADPH oxidase inhibition in diabetes-induced myocardial contractile dysfunction.

Time course of collagen and decorin changes in rat cardiac and skeletal muscle post-MI.

We examined the temporal relationship between messages (type I and type III mRNAs) for the principal fibrillar procollagens and subsequent collagen accretion, cross-linking, and decorin expression in the left ventricle (LV) postmyocardial infarction (post-MI). We sought to determine 1) what role the proteoglycan decorin plays in extracellular matrix (ECM) remodeling known to take place as a consequence of MI and 2) the extent skeletal muscle ECM is altered early post-MI. Therefore, after surgically induced production of small- to moderate-sized infarcts (approximately 20% of LV mass), extent and time course of ECM remodeling was evaluated in remaining viable LV free wall and in slow- [soleus (SOL)] and fast-twitch [gastrocnemius (GAST)] skeletal muscles. Decorin, collagen, and hydroxylysylpyridinium cross-link concentrations and alpha1(I) (type I) and alpha1(III) (type III) procollagen mRNAs were measured in LVs from noninfarcted controls and at 72 h, 1, 2, 5, and 13 wk post-MI. These same data were collected in SOL and GAST muscles at all time points except 13 wk. Type I procollagen mRNA increased at both 72-h and 1-wk time points in LVs. Type III procollagen mRNA was elevated at 1 wk, returning to baseline by 2 wk post-MI. Collagen concentration was significantly increased by 1 wk, more than doubled by 5 wk, and was elevated 129% by 13 wk in the remaining viable LV. LV decorin expression was unaltered at early time points, but increased 38% at 5 wk post-MI and doubled by 13 wk post-MI. In skeletal muscle, procollagen mRNAs were transiently altered in SOL and GAST muscles without any demonstrable effect on the measured ECM parameters. This study reports, for the first time, the upregulation time course of decorin and its relationship to increased HP cross-linking and accumulation of collagen in viable myocardium post-MI.

Exercise training attenuates aging-associated increases in collagen and collagen crosslinking of the left but not the right ventricle in the rat.

The purpose of this study was to compare the independent and interactive effects of age and exercise training on selected parameters of the right ventricle (RV), left ventricular septum (LVS) and left ventricular free-wall (LVFW) extracellular matrix. Specifically, we evaluated collagen and collagen crosslinking (hydroxylysylpyridinoline, HP) concentrations in the myocardial extracellular matrix in young adult, Y (5.5 months) and old, O (25.5 months) male Fischer 344 rats. Rats were assigned to either a sedentary control (YC, OC) or an exercise training group (YT, OT). Rats were trained for 45 min/day, 5 days/week, for 10 weeks at approximately equals 70% of maximal oxygen consumption. Following the training regimen, rats were sacrificed and their hearts were dissected into the RV, LVS and LVFW. Training resulted in a significant hypertrophy of the left ventricle (LV) but not RV relative to body weight. In young rats, collagen concentration was significantly higher (P<0.01) in RV compared to LVS, but not LVFW. With aging, collagen concentration increased significantly (P<0.05) in both ventricles, but more so in LV than RV so that differences in percent collagen observed between chambers in both YC and YT rats no longer existed in OC and OT animals. This aging effect was attenuated by training in the LVS but not the LVFW, so that collagen concentration, while higher in this region of the LV in OT compared to YT rats, was also lower than that seen in the LVS of OC rats. HP crosslink concentration in the LVS and LVFW, but not the RV of OC rats was significantly elevated above corresponding values seen in YC rats (P < 0.05 or greater). In YT rats, training had no effect on HP crosslinking concentration in any of the three regions of the heart. However, in OT rats, training completely prevented the age-associated increase in crosslinking seen in both the LVS and LVFW of OC animals. These findings illustrate the different responses of the RV, LVS and LVFW extracellular matrix components, collagen and HP crosslinking, to both aging and training in the rodent.

Three weeks of Kirschner wire fixation for displaced lateral condylar fractures of the humerus in children.

The authors assessed whether a period of 3 weeks, rather than the commonly used 6 weeks, of smooth Kirschner wire fixation and cast immobilization of the elbow was sufficient to achieve union of displaced fractures of the lateral humeral condyle treated by open reduction. The authors found only one nonunion in a case series of 104 children treated with 3 weeks of fixation. Infections occurred in two children (2%). Late review of 63 children (61%) showed abnormalities of elbow shape in 28 (44%) and wide surgical scars in 43 (68%). The abnormalities of elbow shape were mainly due to overgrowth of the lateral humeral condyle, to the formation of excessive amounts of bone over the outer surface of the condyle, or both. The authors' findings indicate that a period of 3 weeks of smooth Kirschner wire fixation and elbow immobilization is sufficient to achieve healing in most displaced fractures of the lateral humeral condyle treated by open reduction. The findings also indicate that new strategies are needed to reduce the occurrence of overgrowth of the lateral condyle, excessive formation of bone over the condyle, and wide scars.

A 'safe' surgical technique for stabilisation of the sternoclavicular joint: a cadaveric and clinical study.

In symptomatic patients with recurrent anterior sternoclavicular dislocation, surgery may be required to stabilise the joint. Posterior sternoclavicular dislocations may also require open reduction and stabilisation due to the complications that may arise. We present a new, 'safe' technique of surgical stabilisation of the sternoclavicular joint that is not technically demanding and does not require exposure of the first rib, as is often the case in other methods described. The repair was tested in cadavers before being employed in three patients and was found to be effective under both static and dynamic loading. The early clinical results prove encouraging.

Helicopter emergency medical services roles in disaster operations.

Rotor-wing aircraft have previously proven utility in disaster operations, but recent expert reviewers have identified areas of potential improvement in integration of helicopter emergency medical services (HEMS) resources into disaster planning and management. This paper discusses salient points regarding helicopter operations in disaster management, using prior reports regarding rotor-wing aircraft utilization as a basis upon which to provide a concise review of HEMS operations in disasters.

Collagen gene expression in rat left ventricle: interactive effect of age and exercise training.

Whether or not exercise training of sufficient intensity and duration to produce left ventricle (LV) hypertrophy also regulates deposition of interstitial collagen and cross-linking at the pretranslational level is unknown. Therefore, the effects of exercise training on gene expression for the two principal fibrillar collagens in LV, types I and III, were assessed in young adult (5 mo), middle-aged (15 mo), and old (26 mo) rats. We also evaluated the potential interaction of changes in mRNA for these procollagens with alterations in LV extracellular matrix characteristics by simultaneously measuring collagen concentration (hydroxyproline) and extent of mature collagen cross-linking (hydroxylysylpyridinoline, HP). Ten weeks of treadmill running resulted in LV hypertrophy and an increased maximal oxygen uptake in all three age groups of trained rats compared with sedentary controls. Percent collagen in rat LV almost doubled (P < 0.0001) from 5 to 26 mo of age, an increase unaffected by exercise training. With aging, a significant decline in expression of mRNAs for both collagen type I (P < 0.005) and type III (P < 0.001) was observed in LV free wall (LVF) but not septum (LVS). Training prevented this decline in LVF mRNAs for the two principal fibrillar collagens in middle-aged rats whereas it attenuated the decline in senescent animals. HP concentration increased significantly with aging in both LVF (P < 0.005) and LVS (P < 0.01). Training modulated this effect, but again only in LVF, so that HP was significantly lower (P < 0.05) in this region of the LV in old trained rats compared with sedentary counterparts. We conclude that exercise training modulates the effects of aging on collagen gene mRNAs and HP cross-linking regionally within the LV.

Osteitis pubis and instability of the pubic symphysis. When nonoperative measures fail.

Seven rugby players with osteitis pubis and vertical instability at the pubic symphysis were treated operatively after nonoperative treatment had failed to improve their symptoms. The vertical instability was diagnosed based on flamingo view radiographs showing greater than 2 mm of vertical displacement. The players had undergone at least 13 months of nonoperative therapy before surgery was considered. Operative treatment consisted of arthrodesis of the pubic symphysis by bone grafting supplemented by a compression plate. At a mean follow-up of 52.4 months, all patients were free of symptoms and flamingo views confirmed successful arthrodesis with no residual instability of the pubic symphysis. Based on our results with this procedure, we believe that arthrodesis of the pubic symphysis has a role in the treatment of osteitis pubis that is recalcitrant to nonoperative treatment. The combination of osteitis pubis and vertical pubis symphyseal instability may be the cause of failure of nonoperative treatment.