bluuebunny/crossref_metadata_2025 huggingface dataset:
Instructions to Mimic Improve Facial Emotion Recognition in People with Sub-Clinical Autism Traits
Authors: Lewis Michael B. , Dunn Emily
Published: September 2016

People tend to mimic the facial expression of others. It has been suggested that this helps provide social glue between affiliated people but it could also aid recognition of emotions through embodied cognition. The degree of facial mimicry, however, varies between individuals and is limited in people with autism spectrum conditions (ASC). The present study sought to investigate the effect of promoting facial mimicry during a facial-emotion-recognition test. In two experiments, participants without an ASC diagnosis had their autism quotient (AQ) measured. Following a baseline test, they did an emotion-recognition test again but half of the participants were asked to mimic the target face they saw prior to making their responses. Mimicry improved emotion recognition, and further analysis revealed that the largest improvement was for participants who had higher scores on the autism traits. In fact, recognition performance was best overall for people who had high AQ scores but also received the instruction to mimic. Implications for people with ASC are explored.
David Spector: Coordinating gene expression in space and time
Authors: Jordan Shawn
Published: September 2016

Spector’s work focuses on the spatial organization and regulation of gene expression.
Calorie restriction protects against experimental abdominal aortic aneurysms in mice
Authors: Liu Yue , Wang Ting-Ting , Zhang Ran , Fu Wen-Yan , Wang Xu , Wang Fang , Gao Peng , Ding Yang-Nan , Xie Yan , Hao De-Long , Chen Hou-Zao , Liu De-Pei
Published: September 2016

Abdominal aortic aneurysm (AAA), characterized by a localized dilation of the abdominal aorta, is a life-threatening vascular pathology. Because of the current lack of effective treatment for AAA rupture, prevention is of prime importance for AAA management. Calorie restriction (CR) is a nonpharmacological intervention that delays the aging process and provides various health benefits. However, whether CR prevents AAA formation remains untested. In this study, we subjected Apoe−/− mice to 12 wk of CR and then examined the incidence of angiotensin II (AngII)–induced AAA formation. We found that CR markedly reduced the incidence of AAA formation and attenuated aortic elastin degradation in Apoe−/− mice. The expression and activity of Sirtuin 1 (SIRT1), a key metabolism/energy sensor, were up-regulated in vascular smooth muscle cells (VSMCs) upon CR. Importantly, the specific ablation of SIRT1 in smooth muscle cells abolished the preventive effect of CR on AAA formation in Apoe−/− mice. Mechanistically, VSMC-SIRT1–dependent deacetylation of histone H3 lysine 9 on the matrix metallopeptidase 2 (Mmp2) promoter was required for CR-mediated suppression of AngII-induced MMP2 expression. Together, our findings suggest that CR may be an effective intervention that protects against AAA formation.
Simultaneous imaging of local calcium and single sarcomere length in rat neonatal cardiomyocytes using yellow Cameleon-Nano140
Authors: Tsukamoto Seiichi , Fujii Teruyuki , Oyama Kotaro , Shintani Seine A. , Shimozawa Togo , Kobirumaki-Shimozawa Fuyu , Ishiwata Shin’ichi , Fukuda Norio
Published: September 2016

In cardiac muscle, contraction is triggered by sarcolemmal depolarization, resulting in an intracellular Ca2+ transient, binding of Ca2+ to troponin, and subsequent cross-bridge formation (excitation–contraction [EC] coupling). Here, we develop a novel experimental system for simultaneous nano-imaging of intracellular Ca2+ dynamics and single sarcomere length (SL) in rat neonatal cardiomyocytes. We achieve this by expressing a fluorescence resonance energy transfer (FRET)–based Ca2+ sensor yellow Cameleon–Nano (YC-Nano) fused to α-actinin in order to localize to the Z disks. We find that, among four different YC-Nanos, α-actinin–YC-Nano140 is best suited for high-precision analysis of EC coupling and α-actinin–YC-Nano140 enables quantitative analyses of intracellular calcium transients and sarcomere dynamics at low and high temperatures, during spontaneous beating and with electrical stimulation. We use this tool to show that calcium transients are synchronized along the length of a myofibril. However, the averaging of SL along myofibrils causes a marked underestimate (∼50%) of the magnitude of displacement because of the different timing of individual SL changes, regardless of the absence or presence of positive inotropy (via β-adrenergic stimulation or enhanced actomyosin interaction). Finally, we find that β-adrenergic stimulation with 50 nM isoproterenol accelerated Ca2+ dynamics, in association with an approximately twofold increase in sarcomere lengthening velocity. We conclude that our experimental system has a broad range of potential applications for the unveiling molecular mechanisms of EC coupling in cardiomyocytes at the single sarcomere level.
Micro turbine engines for drones propulsion
Authors: Dutczak J
Published: September 2016

Development of micro turbine engines began from attempts of application of that propulsion source by group of enthusiasts of aviation model making. Nowadays, the domain of micro turbojet engines is treated on a par with “full size” aviation constructions. The dynamic development of these engines is caused not only by aviation modellers, but also by use of micro turbojet engines by army to propulsion of contemporary drones, i.e. Unmanned Aerial Vehicles (UAV) or Unmanned Aerial Systems (UAS). On the base of selected examples the state of art in the mentioned group of engines has been presented in the article.
The Financialization of Food?
Authors: Bruno Valentina G. , Büyükşahin Bahattin , Robe Michel A.
Published: September 2016

Commodity‐equity return co‐movements rose dramatically during the Great Recession. This development took place following what has been dubbed the “financialization” of commodity markets. We first document changes since 1995 in the relative importance of financial institutions’ activity in agricultural futures markets. We then use a structural vector autoregression (VAR) model to ascertain the role of that activity in explaining correlations between weekly grain, livestock, and equity returns from 1995–2015. We provide robust evidence that, accounting for shocks that are idiosyncratic to agricultural markets, world business cycle shocks have a substantial and long‐lasting impact on the latter's co‐movements with financial markets. In contrast, changes in the intensity of financial speculation have an impact on cross‐market return linkages that is shorter‐lived and not statistically significant in all model specifications.
The Competition Law and Institutions of the European Union
Authors: Jones Alison , Sufrin Brenda
Published: September 2016

This chapter sketches the history and functions of the EU and its institutions in order to set the EU competition rules in context. It then discusses the competition provisions themselves and explains the way in which those rules are applied and enforced, including the ‘modernisation’ of enforcement by Regulation 1/2003 and how mergers are controlled. It discusses the position and powers of the European Commission, particularly the role of the Competition Directorate General (DG Comp); the powers of the EU Courts; the significance of fundamental rights and the general principles of EU law in competiton cases; the application of competition rules to special sectors; and the application of the EU rules to the EEA.
Introduction to Article 102 TFEU
Authors: Jones Alison , Sufrin Brenda
Published: September 2016

Article 102 TFEU deals with the unilateral conduct of undertakings with substantial market power and prohibits one or more undertakings which hold a dominant position in the internal market or a substantial part of it abusing that position insofar as it may affect inter-Member State trade. This chapter discusses the role of Article 102, the controversy attending its application, and the elements which must be established before the prohibition applies. The chapter examines the meaning of ‘one of more undertakings’, including the concept of collective dominance; the meaning of ‘within the internal market or a substantial part of it’; and the meaning of ‘affect trade between Member States’ including its application to situations where the structure of competition within the EU is threatened. The chapter also discusses the Commission’s review of Article 102 and the publication of its Guidance Paper on enforcement priorities, and the relationship between Article 102 and Article 101. The detailed examination of ‘dominant position’ and ‘abuse’ is left to Chapters 6 and 7 respectively.
Cartels and Oligopoly
Authors: Jones Alison , Sufrin Brenda
Published: September 2016

This chapter examines how EU competition law applies both to undertakings operating cartels and to undertakings that tacitly coordinate their behaviour on an oligopolistic market. It starts by looking at the difference between ‘explicit’ and ‘tacit’ collusion in the light of the theory of games and the ‘prisoners’ dilemma’. The chapter then deals with cartels and other agreements that may be used to bolster cartels, or which may facilitate explicit or tacit collusion on a market. Next, it considers the problem of tacit collusion and whether, in particular, Articles 101 and 102 operate as effective mechanisms for dealing with the oligopoly problem. The chapter also considers other options that EU competition law might offer to deal with tacit collusion, either ex ante or ex post, such as the use of the concept of collective dominance and sector enquiries under Regulation 1/2003, art 17.
Vertical Agreements
Authors: Jones Alison , Sufrin Brenda
Published: September 2016

This chapter, which discusses EU competition policy towards vertical agreements, begins by outlining the choices available to a supplier when deciding how best to market and sell its products or services to customers, and the impact that the competition rules may have on a supplier's choice, including the treatment of agency agreements. It then discusses the EU approach to vertical agreements, in the light of the Commission’s Verticals Guidelines of 2010, including exclusive dealing, single branding, franchising andselective distribution agreements. It considers the importance in EU law of parallel trade between Member States and how this has influenced policy towards vertical restraints. It analyses the application of Article 101(1) and Article 101(3) to vertical agreements, including the Verticals block exemption of 2010; sub-contracting agreements; and the possible application of Article 102 to distribution agreements.
International Aspects
Authors: Jones Alison , Sufrin Brenda
Published: September 2016

This chapter examines the issue of jurisdictional problems in competition law, at the ‘internationalization’ of competition law and the efforts to deal with competition issues at a global level to match the global operations of undertakings on world markets. It looks first at the question of extraterritoriality in public interntional law, particularly the concept of objective territoriality. It considers the distinction between prescriptive jurisdiction and enforcement jurisdiction and how these might apply to competition law. It then looks at the development of the effects doctrine in US law and the concept of comity, and at the position of foreign plaintiffs in US courts. It considers how the EU takes jurisdiction by the application of the single economic entity doctrine and by the development of the implementation doctrine and the qualified effects doctrine. The chapter concludes by examining how international cooperation seeks to help solve jurisdictional problems. It looks at the bilateral agreements into which the EU has entered, and the multilateral cooperation to which the EU is party, including cooperation within UNCTAD, the OECD, the WTO and the International Competition Network (ICN).
Rational design and synthesis of noble-metal nanoframes for catalytic and photonic applications
Authors: Wang Xue , Ruditskiy Aleksey , Xia Younan
Published: September 2016

Nanoframes are unique for their 3D, highly open architecture. When made of noble metals, they are attractive for use as heterogeneous catalysts because of their large specific surface areas, high densities of catalytically active sites and low vulnerability toward sintering. They promise to enhance the catalytic activity and durability while reducing the material loading and cost. For nanoframes composed of Au and/or Ag, they also exhibit highly tunable plasmonic properties similar to those of nanorods. This article presents a brief account of recent progress in the design, synthesis and utilization of noble-metal nanoframes. We start with a discussion of the synthetic strategies, including those involving site-selected deposition and etching, as well as dealloying of both hollow and solid nanocrystals. We then highlight some of the applications enabled by noble-metal nanoframes. Finally, we discuss the challenges and trends with regard to future development.
Repeated Applications of a NonpathogenicStreptomycesStrain Enhance Development of Suppressiveness to Potato Common Scab
Authors: Hiltunen Lea H. , Kelloniemi Jani , Valkonen Jari P. T.
Published: September 2016

Potato common scab caused by several Streptomyces spp. is an important disease with no effective methods of control. Suppressiveness against common scab can develop in soil as a result of long-term potato monoculture and has been associated with nonpathogenic Streptomyces spp. To determine whether the development of scab suppressiveness could be enhanced, the effect of repeated applications of an antagonistic Streptomyces strain on common scab was investigated in a long-term field trial over 5 years. Streptomyces strain 272 applied annually at planting consistently suppressed development of common scab symptoms. On scab-susceptible potato cultivar Bintje, strain 272 reduced disease severity, on average, by 43%; whereas, on the scab-tolerant Nicola, the strain reduced both disease incidence and severity by 43 and 59%, respectively. Regardless of disease pressure, the combined use of strain 272 and the tolerant cultivar reduced the scab coverage to a negligible level. After a single application of strain 272, efficient disease suppression did not persist in the soil to the following growing season. However, when strain 272 was applied in three or more consecutive years, the soil remained suppressive to scab for at least 2 years beyond the last application, suggesting that, with repeated applications, it may be possible to enhance development of scab suppression in soil.
Description of a Novel Monopartite Geminivirus and Its Defective Subviral Genome in Grapevine
Authors: Al Rwahnih Maher , Alabi Olufemi J. , Westrick Nathaniel M. , Golino Deborah , Rowhani Adib
Published: September 2016

A novel virus was detected in grapevines by Illumina sequencing during the screening of two table grape (Vitis vinifera) accessions, cultivars Black Beet and Nagano Purple, from South Korea. The monopartite circular ssDNA genome sequence was subsequently confirmed by rolling cycle amplification, cloning and Sanger sequencing. The complete viral genomic sequence from both accessions ranged from 2,903 to 2,907 nucleotides in length and contained the conserved nonanucleotide sequence TAATATT↓AC and other sequence features typical of the family Geminiviridae, including two predicted sense and four complementary-sense open reading frames. Phylogenetic analysis placed the novel virus in a unique taxon within the family Geminiviridae. A naturally occurring defective subviral DNA was also discovered. This defective DNA molecule carried a deletion of approximately 46% of the full-length genome. Both the genomic and defective DNA molecules were graft-transmissible although no disease is yet correlated with their occurrence in Vitis spp. The tentative names Grapevine geminivirus A (GGVA) and GGVA defective DNA (GGVA D-DNA) are proposed. PCR assays developed using primers designed in the coat protein gene led to the detection of GGVA in 1.74% of 1,262 vines derived from 15 grapevine cultivars from six countries across three continents.
Infant Skin Care Products
Authors: Kuller Joanne McManus
Published: September 2016

Background:

Infant skin is susceptible to dryness and irritation from external factors, including topical skin care products not formulated for the infant's skin. This may increase the risk of contact dermatitis. Parents frequently express concern regarding potential harm from ingredients in skin care products and seek information. This is complicated by several skin care myths.

Purpose:

The purpose of this literature review was to provide evidence-based information to educate parents on the use of products for preterm and term infants.

Search Strategy:

Multiple searches using PubMed were conducted including the search terms “infant skin care,” “infant products,” “infant bath,” “emollients,” “diaper skin care,” and “diaper wipes.” Reference lists of comprehensive reviews were also scanned. Google searches were used to assess consumer information, product information, and regulatory guidelines.

Findings:

There is little scientific evidence to support safety of natural/organic products on infant skin. Raw materials originate from different sources, complicating testing and comparisons of ingredients. Research shows that cleansers formulated for infant skin do not weaken the skin barrier the way harsher soaps and detergents can. Oils with the lowest oleic acid content provide a lower risk of irritant contact dermatitis.

Implications for Practice:

Nurses must be informed about natural and organic products, preservatives, and fragrances and know the definition of commonly used marketing terms.

Implications for Research:

Decisions regarding the use of infant products in preterm and term infants should be evidence based. More research is needed to support claims regarding the safety of products used on infant skin.
Use of Inlet–Obturator Oblique View (Leeds View) for Placement of Posterior Wall Screws in Acetabular Fracture Surgery
Authors: Tosounidis Theodoros H. , Giannoudis Peter V.
Published: September 2016

Posterior wall (PW) fractures are the most common fractures requiring surgical fixation in acetabular surgery. Extra-articular screw placement must be confirmed intraoperatively. Herein we describe the use of the inlet and obturator oblique view (the Leeds view) for screw placement in elementary PW and in associated both-column with PW fractures. We highlight our steps to ensure accurate placement in a small series of patients.
Eccrine Duct Dilation as a Marker of Cicatricial Alopecia
Authors: Tan Timothy , Guitart Joan , Gerami Pedram , Yazdan Pedram
Published: September 2016

Background:

Eccrine duct dilation (EDD) and syringoma-like sweat duct proliferation have been described as reactive changes occurring in a variety of skin conditions. However, extensive evaluation of EDD in scalp biopsies performed for alopecia has not been performed.

Methods:

We retrospectively examined 129 cases of cicatricial alopecia (lichen planopilaris, central centrifugal cicatricial alopecia, and discoid lupus erythematosus) and 130 cases of noncicatricial alopecias (androgenetic alopecia, telogen effluvium, and alopecia areata) for the presence of EDD.

Results:

Overall, EDD occurred in 4% (5/130) of noncicatricial alopecia (2/43 of androgenetic alopecia, 0/15 of telogen effluvium, 3/72 of alopecia areata) and 35% (45/129) of cicatricial alopecia (10/31 of lichen planopilaris, 17/36 central centrifugal cicatricial alopecia, and 18/62 of discoid lupus erythematosus; P < 0.0001) cases.

Conclusions:

EDD can infrequently occur in noncicatricial alopecias; however, the frequency of dilation is significantly increased in cicatricial alopecias. This alteration may be due to compressive or inflammatory effects inherent to the scarring process. The presence of EDD may be a useful adjunctive histopathologic feature in the diagnosis of cicatricial alopecias.
Aggression in Autism Spectrum Disorder: Supporting the Entire Family
Authors: Sabapathy Thusa , Vanderbilt Douglas L. , Zamora Irina , Augustyn Marilyn
Published: September 2016

CASE: Juanita is a 13-year-old non-verbal Latina girl with autism spectrum disorder, moderate intellectual disability, and a seizure disorder whose aggressive behaviors toward her parents have significantly worsened over the past few months.

Juanita's monolingual Spanish-speaking parents are here today for medication management at her primary care clinic. The parents report that Juanita pinches them, pulls their hair, and hits her head with her fists. Her aggression toward them is usually triggered by feelings of frustrations, leaving her parents feeling like they have to walk on eggshells around her and have led to differing parenting styles. Her father reports that he tries to avoid getting her upset and prefers to watch TV with her, whereas her mother takes on the day-to-day caretaking. Although he wants to take a more active role in parenting Juanita, when he tries, Juanita becomes more aggressive and reacts violently toward him.

During the visit, Juanita keeps her eyes downcast, is withdrawn, and some strain is noted between her parents. While speaking to them, Juanita's mother chimes in and reports that she considers herself the primary caregiver and the one who knows her daughter the best. She often dismisses Juanita's father's reporting, saying that “he doesn't know what really is going on.” When Juanita is taken to the restroom by her mother, her father tearfully reports that he feels that it may be best for everyone that he leaves the family because of Juanita's worsening aggression toward him and the toll it is taking on his marriage. How would you approach her management?
Phenotyping, Etiological Factors, and Biomarkers: Toward Precision Medicine in Autism Spectrum Disorders
Authors: Beversdorf David Q. ,   MISSOURI AUTISM SUMMIT CONSORTIUM*
Published: September 2016

Despite the progress made in understanding the biology of autism spectrum disorder (ASD), effective biological interventions for the core symptoms remain elusive. Because of the etiological heterogeneity of ASD, identification of a “one-size-fits-all” treatment approach will likely continue to be challenging. A meeting was convened at the University of Missouri and the Thompson Center to discuss strategies for stratifying patients with ASD for the purpose of moving toward precision medicine. The “white paper” presented here articulates the challenges involved and provides suggestions for future solutions.
An 18-Month Follow-up, Randomized Comparison of Effectiveness and Safety of Two Hyaluronic Acid Fillers for Treatment of Moderate Nasolabial Folds
Authors: Rzany Berthold , Bayerl Christiane , Bodokh Isaac , Boineau Dominique , Dirschka Thomas , Queille-Roussel Catherine , Sebastian Michael , Sommer Boris , Edwartz Carolina , Podda Maurizio
Published: September 2016

BACKGROUND

Hyaluronic acid (HA) filler injection is a popular nonsurgical aesthetic procedure.

OBJECTIVE

To compare the effectiveness and safety of 2 hyaluronic acid fillers (HAEC and HARES) for treatment of moderate nasolabial folds (NLFs).

MATERIALS AND METHODS

This was an evaluator- and subject-blinded split-face study. HAEC or HARES was randomly assigned to the left or right NLF at baseline. Retreatment was performed after 9 months; follow-up extended to 18 months after baseline (9 months after retreatment). Effectiveness assessments included the Wrinkle Severity Rating Scale (WSRS) and subject preference. Safety assessments included adverse events (AEs) and local tolerability symptoms recorded by subjects during 3 weeks after treatment.

RESULTS

HAEC was noninferior to HARES measured as mean change from baseline in WSRS score at 6 months. Mean WSRS score change from baseline was similar between products up to 18 months. A majority of subjects (>70%) were still responders at 18 months (after retreatment at 9 months). The volume required at retreatment was approximately two-thirds of that at baseline. There was no difference in subject preference between products. Both fillers were well tolerated and associated with few treatment-related AEs.

CONCLUSION

HAEC and HARES were effective and well tolerated for treatment of moderate NLFs.
Update on emergency contraception
Authors: Fok Wing Kay , Blumenthal Paul D.
Published: September 2016

Purpose of review

Emergency contraception provides a critical and time-sensitive opportunity for women to prevent undesired pregnancy after intercourse. Both access and available options for emergency contraception have changed over the last several years.

Recent findings

Emergency contraceptive pills can be less effective in obese women. The maximum achieved serum concentration of levonorgestrel (LNG) is lower in obese women than women of normal BMI, and doubling the dose of LNG (3 mg) increases its concentration maximum, approximating the level in normal BMI women receiving one dose of LNG. Repeated use of both LNG and ulipristal acetate (UPA) is well tolerated. Hormonal contraception can be immediately started following LNG use, but should be delayed for 5 days after UPA use to avoid dampening the efficacy of UPA. The copper intrauterine device (IUD) is the only IUD approved for emergency contraception (and the most effective method of emergency contraception), but use of LNG IUD as emergency contraception is currently being investigated. Accurate knowledge about emergency contraception remains low both for patients and healthcare providers.

Emergency contraception is an important yet underutilized tool available to women to prevent pregnancy. Current options including copper IUD and emergency contraceptive pills are safe and well tolerated. Significant gaps in knowledge of emergency contraception on both the provider and user level exist, as do barriers to expedient access of emergency contraception.
Menopausal symptoms and cardiovascular disease mortality in the Women's Ischemia Syndrome Evaluation (WISE)
Authors: Thurston Rebecca C. , Johnson B. Delia , Shufelt Chrisandra L. , Braunstein Glenn D. , Berga Sarah L. , Stanczyk Frank Z. , Pepine Carl J. , Bittner Vera , Reis Steven E. , Thompson Diane V. , Kelsey Sheryl F. , Sopko George , Bairey Merz C. Noel
Published: September 2016

Objective:

Studies have linked vasomotor symptoms (VMS) to markers of cardiovascular disease (CVD) risk, yet few have considered clinical cardiovascular events. Data suggest that associations may depend upon the age that symptoms occur. We examined associations between VMS and cardiovascular events and endothelial function, considering age of symptom onset.

Methods:

The Women's Ischemia Syndrome Evaluation enrolled women referred for coronary angiography for suspected myocardial ischemia. A total of 254 women aged more than 50 years, postmenopausal, with both ovaries, not taking hormone therapy underwent a baseline evaluation, were followed annually (median = 6.0 y), and the National Death Index was searched to ascertain CVD mortality (median = 9.3 y). A subset of participants underwent brachial artery ultrasound for flow-mediated dilation (FMD). Receiver-operating curve analysis was used to determine vasomotor symptom groups (symptoms beginning < age 42 [early onset], beginning ≥42 [later onset], never) which were examined in relation to cardiovascular events and FMD in Cox proportional hazard and linear regression models.

Results:

Women reporting early onset VMS (HR = 3.35, 95% CI = 1.23-7.86, P = 0.005) and women who never had VMS (HR = 2.17, 95% CI = 1.02-4.62, P = 0.05) had higher CVD mortality than women with later onset symptoms (multivariable models). Women with early onset VMS had lower FMD than women with later onset symptoms (b = −4.31, SE = 2.10, P = 0.04, multivariable).

Conclusions:

Women with signs and symptoms of ischemia who had VMS beginning early in midlife had higher CVD mortality and reduced endothelial function relative to women with later onset symptoms. Future research should evaluate the vascular phenotype of women with early midlife VMS.
Trajectories of response to acupuncture for menopausal vasomotor symptoms: the Acupuncture in Menopause study
Authors: Avis Nancy E. , Coeytaux Remy R. , Levine Beverly , Isom Scott , Morgan Timothy
Published: September 2016

Objective:

To examine the trajectories of responses to acupuncture treatment for menopausal vasomotor symptoms (VMS) and the characteristics of women in each trajectory.

Methods:

Two hundred nine perimenopausal and postmenopausal women aged 45 to 60 years experiencing at least four VMS per day were recruited and randomized to receive up to 20 acupuncture treatments within 6 months or to a waitlist control group. The primary outcome was percent change from baseline in the mean daily VMS frequency. Finite mixture modeling was used to identify patterns of percent change in weekly VMS frequencies over the first 8 weeks. The Freeman-Holton test and analysis of variance were used to compare characteristics of women in different trajectories.

Results:

Analyses revealed four distinct trajectories of change in VMS frequency by week 8 in the acupuncture group. A small group of women (11.6%, n = 19) had an 85% reduction in VMS. The largest group (47%, n = 79) reported a 47% reduction in VMS frequency, 37.3% (n = 65) of the sample showed only a 9.6% reduction in VMS frequency, and a very small group (4.1%, n = 7) had a 100% increase in VMS. Among women in the waitlist control group, 79.5% reported a 10% decrease in VMS frequency at week 8. Baseline number of VMS, number of acupuncture treatments in the first 8 weeks, and traditional Chinese medicine diagnosis were significantly related to trajectory group membership in the acupuncture group.

Conclusions:

Approximately half of the treated sample reported a decline in VMS frequency, but identifying clear predictors of clinical response to acupuncture treatment of menopausal VMS remains challenging.
Duration of the menopausal transition is longer in women with young age at onset: the multiethnic Study of Women's Health Across the Nation
Authors: Paramsothy Pangaja , Harlow Siobán D. , Nan Bin , Greendale Gail A. , Santoro Nanette , Crawford Sybil L. , Gold Ellen B. , Tepper Ping G. , Randolph John F.
Published: September 2016

Objective:

The menopausal transition (MT) is a critical period associated with physiologic changes that influence women's long-term health and longevity. Information is, however, limited regarding factors that influence age at the onset of the MT and its duration (ie, time from MT onset to the final menstrual period).

Methods:

We analyzed data for 1,145 women from four sites of the Study of Women's Health Across the Nation who participated in the menstrual calendar substudy, had the start of the MT identified, and had no missing covariate information. Participants included from four racial/ethnic groups: African American, white, Chinese, and Japanese. Women completed daily menstrual calendars from 1996 to 2006 and questions on hormone therapy use monthly. Baseline measures included education, economic strain, and menstrual cycle characteristics. Annual measures included height, weight, and smoking status. Cox proportional hazards models were used to analyze the data.

Results:

The adjusted median duration of the MT ranged from 4.37 years among the oldest age-at-onset quartile to 8.57 years among the youngest age-at-onset quartile (P < 0.001). Cigarette smoking was associated with an earlier onset (P < 0.001) and a shorter duration (P < 0.001). African American women had a longer duration (P = 0.012) than white women. Body mass index was associated with a later onset of the MT (P = 0.001) but not its duration.

Conclusions:

The duration of the MT was largely influenced by the age at which it began: earlier onset was associated with a longer transition. This finding provides a strong rationale for developing improved markers of the onset of the early MT.
Differential expression of systemic inflammatory mediators in amputees with chronic residual limb pain
Authors: Chamessian Alexander , Van de Ven Thomas , Buchheit Thomas , Hsia Hung-Lun , McDuffie Mary , Gamazon Eric R. , Walsh Colin , Bruehl Stephen , Buckenmaier Chester ‘Trip’ , Shaw Andrew
Published: September 2016

Chronic postsurgical pain impacts most amputees, with more than half experiencing neuralgic residual limb pain. The transition from normal acute postamputation pain to chronic residual limb pain likely involves both peripheral and central inflammatory mechanisms. As part of the Veterans Integrated Pain Evaluation Research study, we investigated links between systemic inflammatory mediator levels and chronic residual limb pain. Subjects included 36 recent active duty military traumatic amputees with chronic residual limb pain and 40 without clinically significant pain. Blood samples were obtained and plasma concentrations of an array of inflammatory mediators were analyzed. Residual limb pain intensity and pain catastrophizing were assessed to examine associations with inflammatory mediators. Pro-inflammatory mediators including tumor necrosis factor (TNF)-α, TNF-β, interleukin (IL)-8, ICAM-1, Tie2, CRP, and SAA were elevated in patients with chronic residual limb pain. Across all patients, residual limb pain intensity was associated positively with levels of several proinflammatory mediators (IL-8, TNF-α, IL-12, TNF-β, PIGF, Tie2, SAA, and ICAM-1), and inversely with concentrations of the anti-inflammatory mediator IL-13, as well as IL-2 and Eotaxin-3. Pain catastrophizing correlated positively with IL-8, IL-12, TNF-β, PIGF, and ICAM-1, and inversely with IL-13. Significant associations between catastrophizing and residual limb pain intensity were partially mediated by TNF-α, TNF- β, SAA, and ICAM-1 levels. Results suggest that chronic postamputation residual limb pain is associated with excessive inflammatory response to injury or to inadequate resolution of the postinjury inflammatory state. Impact of pain catastrophizing on residual limb pain may be because of part to common underlying inflammatory mechanisms.
Screening for colorectal cancer: the role of the primary care physician
Authors: Triantafillidis John K. , Vagianos Constantine , Gikas Aristofanis , Korontzi Maria , Papalois Apostolos
Published: September 2016

In recent years, the role of primary care physicians (PCPs) in the diagnosis and management of gastrointestinal disorders, including screening for colorectal cancer (CRC), has been recognized as very important. The available data indicate that PCPs are not adequately following CRC screening guidelines because a number of factors have been identified as significant barriers to the proper application of CRC screening guidelines. These factors include lack of time, patient reluctance, and challenges related to scheduling colonoscopy. Further positive engagement of PCPs with CRC screening is required to overcome these barriers and reach acceptable levels in screening rates. To meet the expectations of modern medicine, PCPs should not only be able to recommend occult blood testing or colonoscopy but also, under certain conditions, able to perform colonoscopy. In this review, the authors aim to provide the current knowledge of the role of PCPs in increasing the rate and successfully implementing a screening program for CRC by applying the relevant international guidelines.
Family Impact and Infant Emotional Outcomes Following Diagnosis of Serious Liver Disease or Transplantation in Infancy
Authors: Bowden Michael R. , Ee Looi C. , Krishnan Usha , O'Loughlin Edward V. , Hardikar Winita , Carmody Diana , Hainsworth Cassandra , Jermyn Vicki , Lee Mee‐Mee , Sawyer Janine , Stormon Michael , Holmes Kathe , Lemberg Daniel A. , Day Andrew S. , Paul Campbell , Hazell Philip
Published: September 2016

Objectives:

Research is lacking into the emotional effects on families of serious chronic illness in infants. We examined the effect of the diagnosis of serious liver disease in infants upon parent psychological symptoms and family functioning. We hypothesized that parent psychological symptoms, family functioning, and father engagement will predict infant emotional outcomes.

Methods:

Parents of infants recently diagnosed with serious liver disease completed validated questionnaires about parent stress, family function, impact of the illness on the family, and father engagement. The measures were repeated after 1 year, with the addition of the Child Behavior Checklist (CBCL).

Results:

Parents of 37 infants participated. Parent stress and family functioning scores were not elevated. Parent psychological symptoms, family function, and father engagement did not predict infant outcome. For mothers, infant diagnosis other than biliary atresia, number of outpatient visits, and impact of the illness on the family explained 32% of the variation in CBCL (P = 0.001). For fathers, socioeconomic status, infant diagnosis other than biliary atresia, whether the infant had had a transplant, and impact of the illness on the family explained 44% of the variation in CBCL (P < 0.001).

Conclusions:

Parents and families appear to be resilient in coping with serious infant illness. Infant diagnosis other than biliary atresia and parental perceptions of high impact of the illness on the family are indicators of negative emotional outcomes for infants with serious liver disease. Psychosocial interventions for infants with chronic illness should target reducing the impact of illness on the family.
Nonmucinous Biliary Epithelium Is a Frequent Finding and Is Often the Predominant Epithelial Type in Mucinous Cystic Neoplasms of the Pancreas and Liver
Authors: Zhelnin Kristen , Xue Yue , Quigley Brian , Reid Michelle D. , Choi Hyejeong , Memis Bahar , Adsay Volkan , Krasinskas Alyssa M.
Published: September 2016

Mucinous cystic neoplasms (MCNs) can occur in the pancreas and liver. Classically, these cystic lesions are lined by columnar mucinous epithelium with underlying ovarian-type stroma. It has been proposed that cysts with ovarian-type stroma and nonmucinous epithelium be considered separate entities in both the pancreas and liver. Using a series of 104 pancreatic and 32 hepatic cases, we aimed to further characterize the epithelium present in MCNs. Mucinous epithelium was defined as pancreatic intraepithelial neoplasia–like columnar cells with pale pink/clear apical mucin. Epithelial cells ranging from flat to cuboidal to short columnar without obvious mucin or goblet cells were classified as nonmucinous/biliary epithelium. A mixture (at least 5%) of mucinous and nonmucinous/biliary epithelium was noted in 81%. Almost half (47%) of the cases had abundant (>50%) nonmucinous/biliary epithelium. Of the 71 cases with ≤50% nonmucinous/biliary epithelium, 8 cases demonstrated high-grade dysplasia (7 pancreas, 1 liver) and 14 demonstrated invasive adenocarcinoma (11 pancreas, 3 liver). Conversely, of the 58 cases with >50% nonmucinous/biliary epithelium, not a single case of high-grade dysplasia (P=0.007) or invasive carcinoma (P<0.001) was identified. In summary, nonmucinous/biliary epithelium frequently occurs in MCNs of the pancreas and liver. As mucinous and nonmucinous/biliary epithelia often occur together, there does not appear to be enough evidence to regard cases with predominantly nonmucinous/biliary epithelium as separate entities. Our findings suggest that mucinous change is a “progression” phenomenon in MCNs of the pancreas and liver, and only when abundant mucinous epithelium is present is there a risk of progression to malignancy.
Double-Blind Randomized Clinical Trial Comparing Dopamine and Epinephrine in Pediatric Fluid-Refractory Hypotensive Septic Shock*
Authors: Ramaswamy Karthik Narayanan , Singhi Sunit , Jayashree Muralidharan , Bansal Arun , Nallasamy Karthi
Published: September 2016

Objective:

We compared efficacy of dopamine and epinephrine as first-line vasoactive therapy in achieving resolution of shock in fluid-refractory hypotensive cold septic shock.

Design:

Double-blind, pilot, randomized controlled study.

Setting:

Pediatric emergency and ICU of a tertiary care teaching hospital.

Patients:

Consecutive children 3 months to 12 years old, with fluid-refractory hypotensive septic shock, were enrolled between July 2013 and December 2014.

Intervention:

Enrolled children were randomized to receive either dopamine (in incremental doses, 10 to 15 to 20 μg/kg/min) or epinephrine (0.1 to 0.2 to 0.3 μg/kg/min) till end points of resolution of shock were achieved. After reaching maximum doses of test drugs, open-label vasoactive was started as per discretion of treating team. Primary outcome was resolution of shock within first hour of resuscitation. The study was registered (CTRI/2014/02/004393) and was approved by institute ethics committee.

Measurements and Main Results:

We enrolled 29 children in epinephrine group and 31 in dopamine group. Resolution of shock within first hour was achieved in greater proportion of children receiving epinephrine (n = 12; 41%) than dopamine (n = 4; 13%) (odds ratio, 4.8; 95% CI, 1.3–17.2; p = 0.019); the trend persisted even at 6 hours (48.3% vs 29%; p = 0.184). Children in epinephrine group had lower Sequential Organ Function Assessment score on day 3 (8 vs 12; p = 0.05) and more organ failure–free days (24 vs 20 d; p = 0.022). No significant difference in adverse events (16.1% vs 13.8%; p = 0.80) and mortality (58.1% vs 48.3%; p = 0.605) was observed between the two groups.

Conclusion:

Epinephrine is more effective than dopamine in achieving resolution of fluid-refractory hypotensive cold shock within the first hour of resuscitation and improving organ functions.
New anti-hepatitis B virus drugs under development and evaluation
Authors: Pan Jiaqian , Tong Shuangmei , Kang Lei , Tang Jing
Published: September 2016

Purpose of review

Although available therapies can effectively inhibit hepatitis B virus (HBV) replication in patients with active chronic hepatitis B (CHB) infection, therapeutic efficacy is limited because of potential drug resistance, and an inability to mediate viral clearance and to rectify immune impairment in CHB patients. This review will summarize the state-of-the-art for anti-HBV drugs and focus on potential drugs and targets under development and evaluation.

Recent findings

New developing drugs are evaluated for their antiviral effects in the areas of interference with the viral replication cycle, elimination of covalently closed circular DNA, modulation of host immunity and identification of the La protein and its regulator casein kinase as possible targets for the development of anti-HBV therapies.

These novel compounds and targets have showed great inhibitory effects on HBV replication in vitro and in animal models. Several novel therapies are promising in early clinical trials. Potentially, combination of newly developing and current antiviral drugs may cure CHB in the clinic.
How much of a problem is resistance in treating hepatitis C?
Authors: Forton Daniel M.
Published: September 2016

Purpose of review

Directly acting antiviral drug (DAA) treatments represent a major advance in hepatitis C management, achieving virological cures in excess of 90%. When treatment failure occurs, it is mostly due to relapse with the emergence of resistance-associated variants.

Recent findings

Data from in-vitro studies and clinical trials have enabled characterization of the amino acid substitutions in antiviral drug targets that confer reduced susceptibility to DAAs. These resistance-associated substitutions (RASs) may exist prior to treatment, and are associated with, but do not inevitably result in, treatment failure. The most important RASs with current regimens occur in the NS5A protein of viral variants, which may persist for years after treatment. The optimal strategy is to prevent resistance through administering the best treatment, appropriately matched to patient and virological characteristics, for example the presence of cirrhosis, prior exposure to interferon and so on.

International treatment guidelines have been developed to select treatments, which may vary in duration and coadministration with ribavirin. Routine resistance testing prior to treatment of naive patients is not generally recommended. Next-generation DAAs will further reduce the emergence of RASs and, because of activity against RASs to currently used DAAs, will be used as rescue therapies for patients who have failed treatment.
Single-molecule imaging of electroporated dye-labelled CheY in liveEscherichia coli
Authors: Di Paolo Diana , Afanzar Oshri , Armitage Judith P. , Berry Richard M.
Published: September 2016

For the past two decades, the use of genetically fused fluorescent proteins (FPs) has greatly contributed to the study of chemotactic signalling inEscherichia coliincluding the activation of the response regulator protein CheY and its interaction with the flagellar motor. However, this approach suffers from a number of limitations, both biological and biophysical: for example, not all fusions are fully functional when fused to a bulky FP, which can have a similar molecular weight to its fused counterpart; they may interfere with the native interactions of the protein and the chromophores of FPs have low brightness and photostability and fast photobleaching rates. A recently developed technique for the electroporation of fluorescently labelled proteins in live bacteria has enabled us to bypass these limitations and study thein vivobehaviour of CheY at the single-molecule level. Here we show that purified CheY proteins labelled with organic dyes can be internalized intoE. colicells in controllable concentrations and imaged with video fluorescence microscopy. The use of this approach is illustrated by showing single CheY molecules diffusing within cells and interacting with the sensory clusters and the flagellar motors in real time.

This article is part of the themed issue ‘The new bacteriology’.
Life: the first two billion years
Authors: Knoll Andrew H. , Bergmann Kristin D. , Strauss Justin V.
Published: September 2016

Microfossils, stromatolites, preserved lipids and biologically informative isotopic ratios provide a substantial record of bacterial diversity and biogeochemical cycles in Proterozoic (2500–541 Ma) oceans that can be interpreted, at least broadly, in terms of present-day organisms and metabolic processes. Archean (more than 2500 Ma) sedimentary rocks add at least a billion years to the recorded history of life, with sedimentological and biogeochemical evidence for life at 3500 Ma, and possibly earlier; phylogenetic and functional details, however, are limited. Geochemistry provides a major constraint on early evolution, indicating that the first bacteria were shaped by anoxic environments, with distinct patterns of major and micronutrient availability. Archean rocks appear to record the Earth's first iron age, with reduced Fe as the principal electron donor for photosynthesis, oxidized Fe the most abundant terminal electron acceptor for respiration, and Fe a key cofactor in proteins. With the permanent oxygenation of the atmosphere and surface oceanca2400 Ma, photic zone O2limited the access of photosynthetic bacteria to electron donors other than water, while expanding the inventory of oxidants available for respiration and chemoautotrophy. Thus, halfway through Earth history, the microbial underpinnings of modern marine ecosystems began to take shape.

This article is part of the themed issue ‘The new bacteriology’.