Showing papers by "State University of Campinas published in 2018"

Minimal information for studies of extracellular vesicles 2018 (MISEV2018) : a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Abstract: The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

Nano based drug delivery systems: recent developments and future prospects

Abstract: Nanomedicine and nano delivery systems are a relatively new but rapidly developing science where materials in the nanoscale range are employed to serve as means of diagnostic tools or to deliver therapeutic agents to specific targeted sites in a controlled manner Nanotechnology offers multiple benefits in treating chronic human diseases by site-specific, and target-oriented delivery of precise medicines Recently, there are a number of outstanding applications of the nanomedicine (chemotherapeutic agents, biological agents, immunotherapeutic agents etc) in the treatment of various diseases The current review, presents an updated summary of recent advances in the field of nanomedicines and nano based drug delivery systems through comprehensive scrutiny of the discovery and application of nanomaterials in improving both the efficacy of novel and old drugs (eg, natural products) and selective diagnosis through disease marker molecules The opportunities and challenges of nanomedicines in drug delivery from synthetic/natural sources to their clinical applications are also discussed In addition, we have included information regarding the trends and perspectives in nanomedicine area

Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer

Abstract: Background Men with nonmetastatic, castration-resistant prostate cancer and a rapidly rising prostate-specific antigen (PSA) level are at high risk for metastasis. We hypothesized that enz...

Sickle cell disease

Abstract: Sickle cell disease (SCD) is a group of inherited disorders caused by mutations in HBB, which encodes haemoglobin subunit β. The incidence is estimated to be between 300,000 and 400,000 neonates globally each year, the majority in sub-Saharan Africa. Haemoglobin molecules that include mutant sickle β-globin subunits can polymerize; erythrocytes that contain mostly haemoglobin polymers assume a sickled form and are prone to haemolysis. Other pathophysiological mechanisms that contribute to the SCD phenotype are vaso-occlusion and activation of the immune system. SCD is characterized by a remarkable phenotypic complexity. Common acute complications are acute pain events, acute chest syndrome and stroke; chronic complications (including chronic kidney disease) can damage all organs. Hydroxycarbamide, blood transfusions and haematopoietic stem cell transplantation can reduce the severity of the disease. Early diagnosis is crucial to improve survival, and universal newborn screening programmes have been implemented in some countries but are challenging in low-income, high-burden settings.

Characterization and engineering of a plastic-degrading aromatic polyesterase

Abstract: Poly(ethylene terephthalate) (PET) is one of the most abundantly produced synthetic polymers and is accumulating in the environment at a staggering rate as discarded packaging and textiles. The properties that make PET so useful also endow it with an alarming resistance to biodegradation, likely lasting centuries in the environment. Our collective reliance on PET and other plastics means that this buildup will continue unless solutions are found. Recently, a newly discovered bacterium, Ideonella sakaiensis 201-F6, was shown to exhibit the rare ability to grow on PET as a major carbon and energy source. Central to its PET biodegradation capability is a secreted PETase (PET-digesting enzyme). Here, we present a 0.92 A resolution X-ray crystal structure of PETase, which reveals features common to both cutinases and lipases. PETase retains the ancestral α/β-hydrolase fold but exhibits a more open active-site cleft than homologous cutinases. By narrowing the binding cleft via mutation of two active-site residues to conserved amino acids in cutinases, we surprisingly observe improved PET degradation, suggesting that PETase is not fully optimized for crystalline PET degradation, despite presumably evolving in a PET-rich environment. Additionally, we show that PETase degrades another semiaromatic polyester, polyethylene-2,5-furandicarboxylate (PEF), which is an emerging, bioderived PET replacement with improved barrier properties. In contrast, PETase does not degrade aliphatic polyesters, suggesting that it is generally an aromatic polyesterase. These findings suggest that additional protein engineering to increase PETase performance is realistic and highlight the need for further developments of structure/activity relationships for biodegradation of synthetic polyesters.

DarkSide-20k: A 20 tonne two-phase LAr TPC for direct dark matter detection at LNGS

Abstract: Building on the successful experience in operating the DarkSide-50 detector, the DarkSide Collaboration is going to construct DarkSide-20k, a direct WIMP search detector using a two-phase Liquid Argon Time Projection Chamber (LAr TPC) with an active (fiducial) mass of 23 t (20 t). This paper describes a preliminary design for the experiment, in which the DarkSide-20k LAr TPC is deployed within a shield/veto with a spherical Liquid Scintillator Veto (LSV) inside a cylindrical Water Cherenkov Veto (WCV). This preliminary design provides a baseline for the experiment to achieve its physics goals, while further development work will lead to the final optimization of the detector parameters and an eventual technical design. Operation of DarkSide-50 demonstrated a major reduction in the dominant 39Ar background when using argon extracted from an underground source, before applying pulse shape analysis. Data from DarkSide-50, in combination with MC simulation and analytical modeling, shows that a rejection factor for discrimination between electron and nuclear recoils of $>3 \times 10^{9}$ is achievable. This, along with the use of the veto system and utilizing silicon photomultipliers in the LAr TPC, are the keys to unlocking the path to large LAr TPC detector masses, while maintaining an experiment in which less than $< 0.1$ events (other than $ u$ -induced nuclear recoils) is expected to occur within the WIMP search region during the planned exposure. DarkSide-20k will have ultra-low backgrounds than can be measured in situ, giving sensitivity to WIMP-nucleon cross sections of $1.2 \times 10^{-47}$ cm2 ( $1.1 \times 10^{-46}$ cm2) for WIMPs of 1 TeV/c2 (10 TeV/c2) mass, to be achieved during a 5 yr run producing an exposure of 100 t yr free from any instrumental background.

The dark energy survey data release 1

Abstract: We describe the first public data release of the Dark Energy Survey, DES DR1, consisting of reduced single-epoch images, co-added images, co-added source catalogs, and associated products and services assembled over the first 3 yr of DES science operations. DES DR1 is based on optical/near-infrared imaging from 345 distinct nights (2013 August to 2016 February) by the Dark Energy Camera mounted on the 4 m Blanco telescope at the Cerro Tololo InterAmerican Observatory in Chile. We release data from the DES wide-area survey covering similar to 5000 deg(2) of the southern Galactic cap in five broad photometric bands, grizY. DES DR1 has a median delivered point-spread function of g = 1.12, r = 0.96, i = 0.88, z = 0.84, and Y = 0.'' 90 FWHM, a photometric precision of <1% in all bands, and an astrometric precision of 151 mas. The median co-added catalog depth for a 1.'' 95 diameter aperture at signal-to-noise ratio (S/N) = 10 is g = 24.33, r = 24.08, i = 23.44, z = 22.69, and Y = 21.44 mag. DES DR1 includes nearly 400 million distinct astronomical objects detected in similar to 10,000 co-add tiles of size 0.534 deg(2) produced from similar to 39,000 individual exposures. Benchmark galaxy and stellar samples contain similar to 310 million and similar to 80 million objects, respectively, following a basic object quality selection. These data are accessible through a range of interfaces, including query web clients, image cutout servers, jupyter notebooks, and an interactive co-add image visualization tool. DES DR1 constitutes the largest photometric data set to date at the achieved depth and photometric precision.

Low-Mass Dark Matter Search with the DarkSide-50 Experiment

Abstract: We present the results of a search for dark matter weakly interacting massive particles (WIMPs) in the mass range below 20 GeV/c2 using a target of low-radioactivity argon with a 6786.0 kg d exposure. The data were obtained using the DarkSide-50 apparatus at Laboratori Nazionali del Gran Sasso. The analysis is based on the ionization signal, for which the DarkSide-50 time projection chamber is fully efficient at 0.1 keVee. The observed rate in the detector at 0.5 keVee is about 1.5 event/keVee/kg/d and is almost entirely accounted for by known background sources. We obtain a 90% C.L. exclusion limit above 1.8 GeV/c2 for the spin-independent cross section of dark matter WIMPs on nucleons, extending the exclusion region for dark matter below previous limits in the range 1.8–6 GeV/c2.

Recent Asian origin of chytrid fungi causing global amphibian declines

Abstract: Globalized infectious diseases are causing species declines worldwide, but their source often remains elusive. We used whole-genome sequencing to solve the spatiotemporal origins of the most devastating panzootic to date, caused by the fungus Batrachochytrium dendrobatidis, a proximate driver of global amphibian declines. We traced the source of B. dendrobatidis to the Korean peninsula, where one lineage, BdASIA-1, exhibits the genetic hallmarks of an ancestral population that seeded the panzootic. We date the emergence of this pathogen to the early 20th century, coinciding with the global expansion of commercial trade in amphibians, and we show that intercontinental transmission is ongoing. Our findings point to East Asia as a geographic hotspot for B. dendrobatidis biodiversity and the original source of these lineages that now parasitize amphibians worldwide.

Adsorption of Pharmaceuticals from Water and Wastewater Using Nonconventional Low-Cost Materials: A Review

Abstract: Pharmaceuticals are environmental contaminants that have been widely detected in aquatic media. In this review, the occurrence of pharmaceuticals in the environment, its major causes, and implications along with effective procedures for their removal from contaminated water have been studied. Adsorption stands out as a promising treatment method, since it offers advantages such as lower energy consumption and simpler operation conditions in comparison to other tertiary treatments. Although commercial activated carbon is extensively studied as an adsorbent of pharmaceuticals, its large-scale application is limited by the high costs. Therefore, different nonconventional low-cost materials have been investigated and adsorbents based on clays, biochars, chitosan, agricultural and industrial wastes, and metal–organic frameworks have been addressed in many studies for pharmaceuticals uptake from water and wastewater. This article reviews key publications on this subject, discussing adsorption performance in ter...

Advances in cellulose nanomaterials

Abstract: Research on nanocellulose has significantly increased over the past few decades, owing to the various attractive characteristics of this material, such as renewability, widespread availability, low density, excellent mechanical properties, economic value, biocompatibility, and biodegradability. Nanocellulose categorized into two main types, namely cellulose nanofibrils (CNFs) and cellulose nanocrystals (CNCs). In this review, we present the recent advances made in the production of CNFs and CNCs. In addition to the conventional mechanical and chemical treatments used to prepare CNFs and CNCs, respectively, other promising techniques as well as pretreatment processes have been also proposed in recent times, in an effort to design an economically efficient and eco-friendly production route for nanocellulose. Further, while the hydrophilic nature of nanocellulose limits its use in polymeric matrices and in some industrial applications, the large number of hydroxyl groups on the surface of nanocellulose provides a suitable platform for various kinds of modification treatments. The various chemical and physical surface treatment procedures reported for nanocellulose have been reviewed in this paper. Finally, in this review, we summarize the life cycle assessment studies conducted so far on nanocellulose, which quantify the environmental impact of nanocellulose products. The current paper is a comprehensive review of the recent literature on nanostructured cellulose.

Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study.

Abstract: Progressive functional decline in the epilepsies is largely unexplained. We formed the ENIGMA-Epilepsy consortium to understand factors that influence brain measures in epilepsy, pooling data from 24 research centres in 14 countries across Europe, North and South America, Asia, and Australia. Structural brain measures were extracted from MRI brain scans across 2149 individuals with epilepsy, divided into four epilepsy subgroups including idiopathic generalized epilepsies (n =367), mesial temporal lobe epilepsies with hippocampal sclerosis (MTLE; left, n = 415; right, n = 339), and all other epilepsies in aggregate (n = 1026), and compared to 1727 matched healthy controls. We ranked brain structures in order of greatest differences between patients and controls, by meta-analysing effect sizes across 16 subcortical and 68 cortical brain regions. We also tested effects of duration of disease, age at onset, and age-by-diagnosis interactions on structural measures. We observed widespread patterns of altered subcortical volume and reduced cortical grey matter thickness. Compared to controls, all epilepsy groups showed lower volume in the right thalamus (Cohen's d = -0.24 to -0.73; P < 1.49 × 10-4), and lower thickness in the precentral gyri bilaterally (d = -0.34 to -0.52; P < 4.31 × 10-6). Both MTLE subgroups showed profound volume reduction in the ipsilateral hippocampus (d = -1.73 to -1.91, P < 1.4 × 10-19), and lower thickness in extrahippocampal cortical regions, including the precentral and paracentral gyri, compared to controls (d = -0.36 to -0.52; P < 1.49 × 10-4). Thickness differences of the ipsilateral temporopolar, parahippocampal, entorhinal, and fusiform gyri, contralateral pars triangularis, and bilateral precuneus, superior frontal and caudal middle frontal gyri were observed in left, but not right, MTLE (d = -0.29 to -0.54; P < 1.49 × 10-4). Contrastingly, thickness differences of the ipsilateral pars opercularis, and contralateral transverse temporal gyrus, were observed in right, but not left, MTLE (d = -0.27 to -0.51; P < 1.49 × 10-4). Lower subcortical volume and cortical thickness associated with a longer duration of epilepsy in the all-epilepsies, all-other-epilepsies, and right MTLE groups (beta, b < -0.0018; P < 1.49 × 10-4). In the largest neuroimaging study of epilepsy to date, we provide information on the common epilepsies that could not be realistically acquired in any other way. Our study provides a robust ranking of brain measures that can be further targeted for study in genetic and neuropathological studies. This worldwide initiative identifies patterns of shared grey matter reduction across epilepsy syndromes, and distinctive abnormalities between epilepsy syndromes, which inform our understanding of epilepsy as a network disorder, and indicate that certain epilepsy syndromes involve more widespread structural compromise than previously assumed.

Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases

Abstract: The recently discovered histone post-translational modification crotonylation connects cellular metabolism to gene regulation. Its regulation and tissue-specific functions are poorly understood. We characterize histone crotonylation in intestinal epithelia and find that histone H3 crotonylation at lysine 18 is a surprisingly abundant modification in the small intestine crypt and colon, and is linked to gene regulation. We show that this modification is highly dynamic and regulated during the cell cycle. We identify class I histone deacetylases, HDAC1, HDAC2, and HDAC3, as major executors of histone decrotonylation. We show that known HDAC inhibitors, including the gut microbiota-derived butyrate, affect histone decrotonylation. Consistent with this, we find that depletion of the gut microbiota leads to a global change in histone crotonylation in the colon. Our results suggest that histone crotonylation connects chromatin to the gut microbiota, at least in part, via short-chain fatty acids and HDACs.

Exfoliation of a non-van der Waals material from iron ore hematite

Abstract: With the advent of graphene, the most studied of all two-dimensional materials, many inorganic analogues have been synthesized and are being exploited for novel applications. Several approaches have been used to obtain large-grain, high-quality materials. Naturally occurring ores, for example, are the best precursors for obtaining highly ordered and large-grain atomic layers by exfoliation. Here, we demonstrate a new two-dimensional material ‘hematene’ obtained from natural iron ore hematite (α-Fe2O3), which is isolated by means of liquid exfoliation. The two-dimensional morphology of hematene is confirmed by transmission electron microscopy. Magnetic measurements together with density functional theory calculations confirm the ferromagnetic order in hematene while its parent form exhibits antiferromagnetic order. When loaded on titania nanotube arrays, hematene exhibits enhanced visible light photocatalytic activity. Our study indicates that photogenerated electrons can be transferred from hematene to titania despite a band alignment unfavourable for charge transfer.

Dark Energy Survey year 1 results: a precise H0 estimate from DES Y1, BAO, and D/H data

Abstract: We combine Dark Energy Survey Year 1 clustering and weak lensing data with baryon acoustic oscillations and Big Bang nucleosynthesis experiments to constrain the Hubble constant. Assuming a flat ΛCDM model with minimal neutrino mass (∑m_ν = 0.06 eV), we find |$H_0=67.4^{+1.1}_{-1.2}\ \rm {km\,\rm s^{-1}\,\rm Mpc^{-1}}$| (68 per cent CL). This result is completely independent of Hubble constant measurements based on the distance ladder, cosmic microwave background anisotropies (both temperature and polarization), and strong lensing constraints. There are now five data sets that: (a) have no shared observational systematics; and (b) each constrains the Hubble constant with fractional uncertainty at the few-per cent level. We compare these five independent estimates, and find that, as a set, the differences between them are significant at the 2.5σ level (χ^2/dof = 24/11, probability to exceed = 1.1 per cent). Having set the threshold for consistency at 3σ, we combine all five data sets to arrive at |$H_0=69.3^{+0.4}_{-0.6}\ \rm {km\,\mathrm{ s}^{-1}\,\mathrm{ Mpc}^{-1}}$|⁠.

The 2018 ISDE achalasia guidelines

Abstract: Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL) The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI) Only statements with an approval rate >80% were accepted in the guidelines Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease

The urban south and the predicament of global sustainability

Abstract: Urbanization is a global phenomenon with strong sustainability implications across multiple scales. We argue that much of the associated challenges, and opportunities, are found in the global south. We show that urban issues in the global south are distinctly and statistically different from those in the global north, but our current urban knowledge is predominantly shaped by research on and from the global north. Cities in the global south have strong imperatives, and unique but often overlooked capacity, to innovate and experiment for sustainability. We call for a renewed research focus on urbanization in the south, and suggest targeted efforts to correct structural biases in the knowledge production system. Most of the sustainability challenges and opportunities associated with urbanization are found in the global south. This Perspective shows the extent to which urban issues differ between the developed and developing worlds and identifies steps to re-focus the urban research system globally in view of allowing a more prominent role of urban scholarship from the global south.

Constraints on sub-GeV dark matter-electron scattering from the DarkSide-50 experiment

Abstract: We present new constraints on sub-GeV dark-matter particles scattering off electrons based on 6780.0 kg d of data collected with the DarkSide-50 dual-phase argon time projection chamber. This analysis uses electroluminescence signals due to ionized electrons extracted from the liquid argon target. The detector has a very high trigger probability for these signals, allowing for an analysis threshold of three extracted electrons, or approximately 0.05 keVee. We calculate the expected recoil spectra for dark matter-electron scattering in argon and, under the assumption of momentum-independent scattering, improve upon existing limits from XENON10 for dark-matter particles with masses between 30 and 100 MeV/c^{2}.

Bologna guidelines for diagnosis and management of adhesive small bowel obstruction (ASBO): 2017 update of the evidence-based guidelines from the world society of emergency surgery ASBO working group

Abstract: Adhesive small bowel obstruction (ASBO) is a common surgical emergency, causing high morbidity and even some mortality. The adhesions causing such bowel obstructions are typically the footprints of previous abdominal surgical procedures. The present paper presents a revised version of the Bologna guidelines to evidence-based diagnosis and treatment of ASBO. The working group has added paragraphs on prevention of ASBO and special patient groups. The guideline was written under the auspices of the World Society of Emergency Surgery by the ASBO working group. A systematic literature search was performed prior to the update of the guidelines to identify relevant new papers on epidemiology, diagnosis, and treatment of ASBO. Literature was critically appraised according to an evidence-based guideline development method. Final recommendations were approved by the workgroup, taking into account the level of evidence of the conclusion. Adhesion formation might be reduced by minimally invasive surgical techniques and the use of adhesion barriers. Non-operative treatment is effective in most patients with ASBO. Contraindications for non-operative treatment include peritonitis, strangulation, and ischemia. When the adhesive etiology of obstruction is unsure, or when contraindications for non-operative management might be present, CT is the diagnostic technique of choice. The principles of non-operative treatment are nil per os, naso-gastric, or long-tube decompression, and intravenous supplementation with fluids and electrolytes. When operative treatment is required, a laparoscopic approach may be beneficial for selected cases of simple ASBO. Younger patients have a higher lifetime risk for recurrent ASBO and might therefore benefit from application of adhesion barriers as both primary and secondary prevention. This guideline presents recommendations that can be used by surgeons who treat patients with ASBO. Scientific evidence for some aspects of ASBO management is scarce, in particular aspects relating to special patient groups. Results of a randomized trial of laparoscopic versus open surgery for ASBO are awaited.

Geant4-DNA example applications for track structure simulations in liquid water: A report from the Geant4-DNA Project.

Abstract: This Special Report presents a description of Geant4-DNA user applications dedicated to the simulation of track structures (TS) in liquid water and associated physical quantities (e.g., range, stopping power, mean free path…). These example applications are included in the Geant4 Monte Carlo toolkit and are available in open access. Each application is described and comparisons to recent international recommendations are shown (e.g., ICRU, MIRD), when available. The influence of physics models available in Geant4-DNA for the simulation of electron interactions in liquid water is discussed. Thanks to these applications, the authors show that the most recent sets of physics models available in Geant4-DNA (the so-called "option4" and "option 6" sets) enable more accurate simulation of stopping powers, dose point kernels, and W-values in liquid water, than the default set of models ("option 2") initially provided in Geant4-DNA. They also serve as reference applications for Geant4-DNA users interested in TS simulations.

An Indication of Anisotropy in Arrival Directions of Ultra-high-energy Cosmic Rays through Comparison to the Flux Pattern of Extragalactic Gamma-Ray Sources

Abstract: A new analysis of the data set from the Pierre Auger Observatory provides evidence for anisotropy in the arrival directions of ultra-high-energy cosmic rays on an intermediate angular scale, which is indicative of excess arrivals from strong, nearby sources. The data consist of 5514 events above 20 EeV with zenith angles up to 80 recorded before 2017 April 30. Sky models have been created for two distinct populations of extragalactic gamma-ray emitters: active galactic nuclei from the second catalog of hard Fermi-LAT sources (2FHL) and starburst galaxies from a sample that was examined with Fermi-LAT. Flux-limited samples, which include all types of galaxies from the Swift-BAT and 2MASS surveys, have been investigated for comparison. The sky model of cosmic-ray density constructed using each catalog has two free parameters, the fraction of events correlating with astrophysical objects, and an angular scale characterizing the clustering of cosmic rays around extragalactic sources. A maximum-likelihood ratio test is used to evaluate the best values of these parameters and to quantify the strength of each model by contrast with isotropy. It is found that the starburst model fits the data better than the hypothesis of isotropy with a statistical significance of 4.0σ, the highest value of the test statistic being for energies above 39 EeV. The three alternative models are favored against isotropy with 2.7σ-3.2σ significance. The origin of the indicated deviation from isotropy is examined and prospects for more sensitive future studies are discussed.