Do Direct Detection Experiments Constrain Axionlike Particles Coupled to Electrons?

Several laboratory experiments have published limits on axionlike particles (ALPs) with feeble couplings to electrons and masses in the kilo-electron-volt to mega-electron-volt range, under the assumption that such ALPs comprise the dark matter. We note that ALPs decay radiatively into photons, and show that for a large subset of the parameter space ostensibly probed by these experiments, the lifetime of the ALPs is shorter than the age of the Universe. Such ALPs cannot consistently make up the dark matter, which significantly affects the interpretation of published limits from GERDA, Edelweiss-III, SuperCDMS, and Majorana. Moreover, constraints from x-ray and γ-ray astronomy exclude a wide range of the ALP-electron coupling, and supersede all current laboratory limits on dark matter ALPs in the 6 keV to 1 MeV mass range. These conclusions are rather model independent, and can only be avoided at the expense of significant fine-tuning in theories where the ALP has additional couplings to other particles.

Interferon-Induced Transmembrane Protein 1 Restricts Replication of Viruses That Enter Cells via the Plasma Membrane.

The acute antiviral response is mediated by a family of interferon-stimulated genes (ISGs), providing cell-intrinsic immunity. Mutations in genes encoding these proteins are often associated with increased susceptibility to viral infections. One family of ISGs with antiviral function is the interferon-inducible transmembrane proteins (IFITMs), of which IFITM3 has been studied extensively. In contrast, IFITM1 has not been studied in detail. Since IFITM1 can localize to the plasma membrane, we investigated its function with a range of enveloped viruses thought to infect cells by fusion with the plasma membrane. Overexpression of IFITM1 prevented infection by a number of Paramyxoviridae and Pneumoviridae, including respiratory syncytial virus (RSV), mumps virus, and human metapneumovirus (HMPV). IFITM1 also restricted infection with an enveloped DNA virus that can enter via the plasma membrane, herpes simplex virus 1 (HSV-1). To test the importance of plasma membrane localization for IFITM1 function, we identified blocks of amino acids in the conserved intracellular loop (CIL) domain that altered the subcellular localization of the protein and reduced antiviral activity. By screening reported data sets, 12 rare nonsynonymous single nucleotide polymorphisms (SNPs) were identified in human IFITM1, some of which are in the CIL domain. Using an Ifitm1-/- mouse, we show that RSV infection was more severe, thereby extending the range of viruses restricted in vivo by IFITM proteins and suggesting overall that IFITM1 is broadly antiviral and that this antiviral function is associated with cell surface localization.IMPORTANCE Host susceptibility to viral infection is multifactorial, but early control of viruses not previously encountered is predominantly mediated by the interferon-stimulated gene (ISG) family. There are upwards of 300 of these genes, the majority of which do not have a clearly defined function or mechanism of action. The cellular location of these proteins may have an important effect on their function. One ISG located at the plasma membrane is interferon-inducible transmembrane protein 1 (IFITM1). Here we demonstrate that IFITM1 can inhibit infection with a range of viruses that enter via the plasma membrane. Mutant IFITM1 proteins that were unable to localize to the plasma membrane did not restrict viral infection. We also observed for the first time that IFITM1 plays a role in vivo, and Ifitm1-/- mice were more susceptible to viral lung infection. These data contribute to our understanding of how ISGs prevent viral infections.

Evaluating the communities care program: best practice for rigorous research to evaluate gender based violence prevention and response programs in humanitarian settings.

BACKGROUND: Gender-based violence (GBV) is a significant issue for women and girls in humanitarian settings. Innovative primary prevention programs are being developed and implemented with existing response programs to change harmful social norms that sustain GBV in humanitarian settings. Social norms are expectations of how women, men, girls and boys should behave, who should have power and control over behavior, and how families and communities value women and girls and support their rights and opportunities. METHODS: The United Nations Children's Fund (UNICEF) led Communities Care program is a primary prevention and response program designed from the understanding that within the context of conflict and displacement, there is an opportunity for positive change in social norms that support gender equity, and decrease GBV. The goal is to support communities in humanitarian settings to create healthy, safe and peaceful environments with quality response services for women and girls by transforming harmful social norms that uphold violence into norms that promote dignity, equity, and non-violence. CONCLUSION: This manuscript will highlight the use of best practices in GBV research to rigorously evaluate the Communities Care program in two diverse in humanitarian settings, Somalia and South Sudan.

Directed evolution of the periodic table: probing the electronic structure of late actinides.

Recent investigations of the coordination chemistry and physical properties of berkelium (Z = 97) and californium (Z = 98) have revealed fundamental differences between post-curium elements and lighter members of the actinide series. This review highlights these developments and chronicles key findings and concepts from the last half-century that have helped usher in a new understanding of the evolution of electronic structure in the periodic table.

Exacerbating the Cosmological Constant Problem with Interacting Dark Energy Models.

Future cosmological surveys will probe the expansion history of the Universe and constrain phenomenological models of dark energy. Such models do not address the fine-tuning problem of the vacuum energy, i.e., the cosmological constant problem (CCP), but can make it spectacularly worse. We show that this is the case for "interacting dark energy" models in which the masses of the dark matter states depend on the dark energy sector. If realized in nature, these models have far-reaching implications for proposed solutions to the CCP that require the number of vacua to exceed the fine-tuning of the vacuum energy density. We show that current estimates of the number of flux vacua in string theory, N_{vac}∼O(10^{272 000}), are far too small to realize certain simple models of interacting dark energy and solve the cosmological constant problem anthropically. These models admit distinctive observational signatures that can be targeted by future gamma-ray observatories, hence making it possible to observationally rule out the anthropic solution to the cosmological constant problem in theories with a finite number of vacua.

Simple Emergent Power Spectra from Complex Inflationary Physics.

We construct ensembles of random scalar potentials for N_{f}-interacting scalar fields using nonequilibrium random matrix theory, and use these to study the generation of observables during small-field inflation. For N_{f}=O(few), these heavily featured scalar potentials give rise to power spectra that are highly nonlinear, at odds with observations. For N_{f}≫1, the superhorizon evolution of the perturbations is generically substantial, yet the power spectra simplify considerably and become more predictive, with most realizations being well approximated by a linear power spectrum. This provides proof of principle that complex inflationary physics can give rise to simple emergent power spectra. We explain how these results can be understood in terms of large N_{f} universality of random matrix theory.

IFITM proteins-cellular inhibitors of viral entry.

Interferon inducible transmembrane (IFITM) proteins are a recently discovered family of cellular anti-viral proteins that restrict the replication of a number of enveloped and non-enveloped viruses. IFITM proteins are located in the plasma membrane and endosomal membranes, the main portals of entry for many viruses. Biochemical and membrane fusion studies suggest IFITM proteins have the ability to inhibit viral entry, possibly by modulating the fluidity of cellular membranes. Here we discuss the IFITM proteins, recent work on their mode of action, and future directions for research.

Excess astrophysical photons from a 0.1-1 keV cosmic axion background.

Primordial decays of string theory moduli at z~10(12) naturally generate a dark radiation cosmic axion background with 0.1-1 keV energies. This cosmic axion background can be detected through axion-photon conversion in astrophysical magnetic fields to give quasithermal excesses in the extreme ultraviolet and soft x-ray bands. Substantial and observable luminosities may be generated even for axion-photon couplings <<10(-11) GeV(-1). We propose that axion-photon conversion may explain the observed excess emission of soft x rays from galaxy clusters, and may also contribute to the diffuse unresolved cosmic x-ray background. We list a number of correlated predictions of the scenario.

Differences between X-ray and MRI-determined knee cartilage thickness in weight-bearing and non-weight-bearing conditions.

OBJECTIVE: Determine the effect of loading upon MRI-based mean medial femorotibial cartilage thickness (mMFT_th) and radiograph-based minimum joint space width (mJSW), and determine loading's effect on the relationship between these measures. METHODS: MRI and radiographs were analyzed of 25 knees in weight-bearing and non-weight-bearing conditions. Eight subjects had a Kellgren-Lawrence (KL) grade of 0, indicating no evidence of radiographic OA. The rest were KL = 2 or KL = 3, indicating mild to moderate OA. The change from unloaded to loaded conditions was calculated. RESULTS: Joint space measures decreased from unloaded to loaded conditions for both radiographs (mJSW = 3.29 mm unloaded to 3.16 mm loaded, P < 0.05) and MRI (mMFT_th = 2.70 mm unloaded to 2.55 mm loaded P < 0.001). The mean absolute difference measured from radiographs was larger for the OA group than the control group, at -0.20 mm for OA vs +0.01 mm for control. Loaded X-ray and loaded MRI joint space values from our study were no better correlated to one another than loaded X-ray and unloaded MRI. CONCLUSION: Knee loading does not add a very significant value to the study of joint space on healthy knees, but loading may play a role in the study of OA knees. Unloaded MRI assessments of cartilage thickness are as correlated to loaded JSW as to loaded MRI measurements. More study is necessary to determine whether loaded MRI adds significant value to the study of OA progression.

Women's views on and adherence to low-molecular-weight heparin therapy during pregnancy and the puerperium.

BACKGROUND: Non-adherence to prescribed medication represents a significant factor associated with treatment failure. Pregnant women identified at risk of venous thromboembolism are increasingly being prescribed low-molecular-weight heparin (LMWH) during pregnancy and the puerperium. It is important to understand women's views on and adherence to LMWH during pregnancy and the puerperium, so that women gain maximum benefit from the treatment. OBJECTIVES: To monitor women's adherence to enoxaparin, when prescribed during pregnancy and the puerperium, and explore their beliefs about the enoxaparin therapy prescribed. PATIENTS/METHODS: A prospective cohort study involving 95 nullparous and multiparous women prescribed enoxaparin for recognized antenatal indications. Adherence to enoxaparin was assessed through self-completion of a diary, additionally verified through laboratory tests. An adapted beliefs about medication questionnaire was administered to women during their pregnancy. RESULTS: Women were highly adherent to enoxaparin: antenatally, mean percentage adherence 97.92%; postnatally, mean percentage adherence 93.37% (paired t-test, P = 0.000). In the cohort of women we followed, their perceived necessity for enoxaparin therapy outweighed any concerns they had regarding enoxaparin antenatally, necessity-concerns differential 2.20. In some women, however, this perceived necessity does decrease postnatally. CONCLUSIONS: Our results suggest that most women prescribed enoxaparin are highly adherent to their therapy during the antenatal period and that women's antenatal beliefs about enoxaparin are able to predict a decrease in postnatal adherence. Our results have important clinical implications, particularly when women are initiated on LMWH just during the postnatal period.

Poster - Thur Eve - 44: Digital tomosynthesis image quality in a Co-60 treatment beam.

Image guidance capability is an important feature of modern radiotherapy machines. Cobalt-60 units will require some form of image guidance if they are to be brought up to modern standards. Imaging in the treatment beam is an appealing option, for reasons of simplicity and cost, but the dose needed to produce cone beam CT images in a Co-60 treatment beam is too high for this modality to be clinically useful. Digital tomosynthesis (DT) offers a quasi-3D image, of sufficient quality to identify bony anatomy or fiducial markers, while delivering a much lower dose than CBCT. A series of experiments were conducted on a prototype Co-60 cone beam imaging system to quantify the resolution, selectivity, geometric accuracy and contrast sensitivity of Co-60 DT. Although the resolution was severely limited by the penumbra cast by the ∼2cm diameter source, it was possible to identify high contrast objects on the order of 1 mm in width, and bony anatomy in anthropomorphic phantoms was clearly recognizable. Low contrast sensitivity down to electron density differences of 3% was obtained, for uniform features of similar thickness. The conventional shift-and-add algorithm was compared to the FDK filtered backprojection algorithm using several different spatial filters. The Co-60 DT images were obtained with a total dose of 5 to 15 cGy. We conclude that, should Co-60 radiotherapy units be upgraded with image guidance capabilities, filtered backprojection DT in the treatment beam is a versatile and promising modality that would be well suited to the task of patient positioning.

Changes in the maternal hypothalamic-pituitary-adrenal axis during the early puerperium may be related to the postpartum 'blues'.

Most women experience time-limited and specific mood changes in the days after birth known as the maternity blues (Blues). The maternal hypothalamic-pituitary-adrenal (HPA) axis undergoes gradual changes during pregnancy because of an increasing production of placental corticotrophin-releasing hormone (CRH). The abrupt withdrawal of placental CRH at birth results in a re-equilibration of the maternal HPA axis in the days post-delivery. These changes may be involved in the aetiology of the Blues given the central role of the HPA axis in the aetiology of mood disorders in general, and in perinatal depression in particular. We aimed to test the novel hypothesis that the experience of the Blues may be related to increased secretion of hypothalamic adrenocorticotrophic hormone (ACTH) secretagogue peptides, after the reduction in negative-feedback inhibition on the maternal hypothalamus caused by withdrawal of placental CRH. We therefore examined hormonal changes in the HPA axis in the days after delivery in relation to daily mood changes: our specific prediction was that mood changes would parallel ACTH levels, reflecting increased hypothalamic peptide secretion. Blood concentrations of CRH, ACTH, cortisol, progesterone and oestriol were measured in 70 healthy women during the third trimester of pregnancy, and on days 1-6 post-delivery. Blues scores were evaluated during the postpartum days. Oestriol, progesterone and CRH levels fell rapidly from pregnancy up to day 6, whereas cortisol levels fell modestly. ACTH concentrations declined from pregnancy to day 3 post-delivery and thereafter increased up to day 6. Blues scores increased, peaking on day 5, and were positively correlated with ACTH; and negatively correlated with oestriol levels during the postpartum days, and with the reduction in CRH concentrations from pregnancy. These findings give indirect support to the hypothesis that the 'reactivation' of hypothalamic ACTH secretagogue peptides may be involved in the aetiology of the Blues.

Diacylglycerol kinase α regulates the formation and polarisation of mature multivesicular bodies involved in the secretion of Fas ligand-containing exosomes in T lymphocytes.

Multivesicular bodies (MVBs) are endocytic compartments that contain intraluminal vesicles formed by inward budding from the limiting membrane of endosomes. In T lymphocytes, these vesicles contain pro-apoptotic Fas ligand (FasL), which may be secreted as 'lethal exosomes' upon fusion of MVBs with the plasma membrane. Diacylglycerol kinase α (DGKα) regulate the secretion of exosomes, but it is unclear how this control is mediated. T-lymphocyte activation increases the number of MVBs that contain FasL. DGKα is recruited to MVBs and to exosomes in which it has a double function. DGKα kinase activity exerts a negative role in the formation of mature MVBs, as we demonstrate by the use of an inhibitor. Downmodulation of DGKα protein resulted in inhibition of both the polarisation of MVBs towards immune synapse and exosome secretion. The subcellular location of DGKα together with its complex role in the formation and polarised traffic of MVBs support the notion that DGKα is a key regulator of the polarised secretion of exosomes.

Increased pituitary-adrenal activation and shortened gestation in a sample of depressed pregnant women: a pilot study.

BACKGROUND: Major depression (MD) is frequently accompanied by a relatively increased production of the stress hormone cortisol. During pregnancy corticotrophin releasing hormone (CRH) is secreted from the placenta and critically high levels of CRH are one of the key triggers for parturition. Maternal cortisol promotes the secretion of placental CRH. In this study, we examined the hypothesis that women suffering with MD in pregnancy would have relatively increased cortisol secretion, a time-advanced rise in placental CRH production and an earlier delivery of the baby. METHODS: A group of medication-free pregnant women, free of know obstetric and medical complications, with (n=27) and without (n=38) MD were recruited. Blood concentrations of CRH, adrenocorticotrophic hormone (ACTH) and diurnal salivary cortisol concentrations were measured at fixed time points. RESULTS: Maternal cortisol concentrations were highly correlated with placental CRH secretion for the entire group. Second trimester CRH concentrations and mean evening salivary cortisol concentrations were significantly higher in the depressed women. Although pregnancy length was shorter in the depressed women there were no statistical relationships between the stress hormone measures and pregnancy length. LIMITATIONS: The sample size was small and highly selected. CONCLUSIONS: These findings suggest that depressed pregnant women hypersecrete cortisol in a diurnal pattern similar to that typical of MD, and that this leads to a time-advanced rise in placental CRH secretion. Factors other than this stress-delivery mechanism may be contributing to the shortened pregnancy length in depressed women.

The effect of estrone on thrombin generation may explain the different thrombotic risk between oral and transdermal hormone replacement therapy.

BACKGROUND: The metabolism of estrogen contained within hormone replacement therapy (HRT) is influenced by the route of administration, and this may affect the risk of venous thromboembolism. Thrombin generation, a global coagulation assay, is a marker of hypercoagulability and is of potential use in determining the thrombotic risk associated with particular HRT administration routes. OBJECTIVES: To determine whether any effect of oral and transdermal HRT on thrombin generation is related to the plasma estrogen profile. METHODS: We investigated the effects of oral, transdermal and no HRT (controls) in 52, 39 and 52 postmenopausal women, respectively, on thrombin generation, standard markers of thrombophilia, estradiol level and estrone level. RESULTS: All parameters of thrombin generation were altered in women using oral HRT as compared with controls (P<0.001 for all comparisons). No such differences were found in women using transdermal HRT. Estrone levels correlated with peak thrombin generation (R=0.451, P<0.001) in women using oral HRT, but there was no correlation in women using the transdermal route. CONCLUSIONS: Thrombin generation is significantly increased in women who use HRT administered by the oral route. This is probably mediated by the hepatic first-pass metabolism of estrone, the main metabolite of oral estradiol, which is avoided by the transdermal route. The effect of estrone on thrombin generation may provide the explanation for the higher thrombotic risk seen in women using oral rather than transdermal HRT.

Early postoperative care for free flap head & neck reconstructive surgery--a national survey of practice.

There is considerable variation in the post-operative management of head and neck free flaps in the UK. We undertook a national postal survey of maxillofacial surgical units in the UK who perform free flap reconstruction following ablative head and neck surgery. Questions were asked about the routine postoperative care of a hypothetical, straightforward patient undergoing free flap reconstruction to determine whether there were any trends in managing these patients. There was considerable variation in the number of free flaps performed by each unit per year. The majority of patients (87%) are managed in either an intensive care or high dependency unit. The routine use of a tracheostomy is common (69%). There was also variation in the management of these cases, particularly with the requirement for ventilation. Few units routinely use dextran or dobutamine infusions, although one-to-one nursing and invasive cardiovascular monitoring are commonplace. Alternative provision of postoperative care is discussed.