Is Pregnancy-Associated Melanoma Associated with Adverse Outcomes?

BACKGROUND: Melanoma is the most common malignancy encountered during pregnancy. Conflicting data have led to ongoing confusion regarding pregnancy-associated melanoma (PAM) in the media and among the public. The objective of this study was to better characterize both the clinical presentation of PAM and its prognostic implications. STUDY DESIGN: Female patients of reproductive age, with stage 0 to IV cutaneous melanoma, were identified from our prospectively maintained database. Clinical and histopathologic factors were analyzed with appropriate statistical methods. Univariable and then multivariable analysis were used on matched data to compare disease-free survival (DFS), overall survival (OS), and melanoma-specific survival (MSS) for stage 0-III PAMs vs non-PAMs. Kaplan-Meier survival curves were then plotted for OS and MSS and compared using the log-rank test. RESULTS: The clinical presentation of melanoma was similar for PAM and non-PAM patients. There was no significant difference in recurrence between the 2 groups; for PAM patients, 38.5% of patients had recurrence, as compared with 36.6% of non-PAM patients (p = 0.641). For PAM patients, median follow-up was 14.6 years (range 0 to 42.6 years) and 11.1 years (0 to 48.5 years) for the non-PAM patients. No significant differences in DFS, MSS, or OS were identified on univariable or multivariable analysis for PAM vs non-PAM patients in stage 0/I/II and stage III cutaneous melanoma, respectively (p = 0.880 DFS, p = 0.219 OS, and p = 0.670 MSS). CONCLUSIONS: We observed no difference in DFS, OS, or MSS between the 2 groups. Pregnant patients should be screened for melanoma in a similar manner to nonpregnant patients and should be counseled that their survival is not adversely affected by their pregnancy

Community Participation Among Individuals with Serious Mental Illnesses Leaving Jail

Studies have found that higher levels of community participation are associated with a number of positive outcomes such as increased recovery and quality of life. People with serious mental illnesses (SMI) leaving jail face a number of barriers that limit their ability to participate in community activities. In this paper we examine whether the combined experience of mental illness and recent discharge from jail furthers the community isolation that is already experienced by individuals with serious mental illnesses. This analysis found that people with SMI recently released from jail had significantly lower levels of community participation in terms of overall number of community participation days and activities, number of time spent in activities individuals identified as important, and on measures of sufficiency related to the time spent engaged in these activities. Community participation is a key component of community re-integration for people with SMI leaving jail. The results of this study show that services for people with SMI leaving jail need to include interventions that foster engagement in community based activities

SPIFI: a Direct-Detection Imaging Spectrometer for Submillimeter Wavelengths

The South Pole Imaging Fabry-Perot Interferometer (SPIFI) is the first instrument of its kind -a direct-detection imaging spectrometer for astronomy in the submillimeter band. SPIFI ’s focal plane is a square array of 25 silicon bolometers cooled to 60 mK; the spectrometer consists of two cryogenic scanning Fabry-Perot interferometers in series with a 60-mK bandpass filter. The instrument operates in the short submillimeter windows (350 and 450 μm) available from the ground, with spectral resolving power selectable between 500 and 10,000. At present, SPIFI’s sensitivity is within a factor of 1.5-3 of the photon background limit, comparable with the best heterodyne spectrometers. The instrument ’s large bandwidth and mapping capability provide substantial advantages for specific astrophysical projects, including deep extragalactic observations. We present the motivation for and design of SPIFI and its operational characteristics on the telescope

The effects of self-efficacy, perceptions of ethical misconduct, and guilt-proneness on CWBs

This study examined the relationship between generalized self-efficacy, perceptions of ethical misconduct, guilt-proneness, and counterproductive work behaviors. We first hypothesized that self-efficacy would be negatively related to counterproductive work behaviors. Secondly, we hypothesized that perceptions of ethical misconduct and levels of guilt-proneness would mediate the negative relationship between generalized self-efficacy and counterproductive work behaviors. We surveyed 190 undergraduate students. To test our hypotheses, we used serial mediation (self-efficacy perceptions of ethical misconduct Guilt CWBs). Results supported our first hypothesis. However, we did not find support for the mediated relationship proposed in our second hypothesis

Hijerarhije sinergija u ljudskim pokretima

This brief review addresses the problem of motor redundancy, which exists at many levels of the neuro-motor hierarchies involved in the production of voluntary movements. An approach to this problem is described based on the principle of abundance. This approach offers an operational definition for motor synergies using the framework of the uncontrolled manifold hypothesis. It is shown that hierarchical systems have inherent trade-offs between synergies at different control levels. These trade-offs have been demonstrated in experimental studies of human multi-finger pressing and prehension. They are likely to be present in other hierarchical systems, for example, those involved in the control of large groups of muscles. The framework of the equilibrium-point hypothesis offers a physiologically based mechanism, which may form the basis for hierarchies of synergies.Ovaj se pregledni rad bavi problemom motoričke redundancije (zalihosti) koja postoji na više razina neuromotoričkih hijerarhija uključenih u realizaciju voljnih pokreta. Opisan je pristup utemeljen na principu obilja (brojnosti). Pristup nudi operativnu definiciju za motoričke sinergije korištenjem okvira što ga pruža hipoteza neupravljanih slojeva (ljusaka). Pokazuje se da hijerarhijski sustavi posjeduju inherentne kompromise između sinergija na različitim razinama upravljanja. Ti se kompromisi mogu pokazati pomoću eksperimentalnih studija pritiska prstima ljudske šake. Vjerojatno je da su isti prisutni i u drugim hijerarhijskim sustavima, npr. onima uključenima u upravljanje velikim skupinama mišića. Okvir hipoteze ravnotežne točke nudi fiziološki utemeljen mehanizam koji može predstavljati osnovu za hijerarhije sinergija. Problem motoričke redundancije Svi neuromotorički procesi unutar ljudskoga ti-jela povezani s izvođenjem prirodnih voljnih pokreta uključuju nekoliko preslikavanja (mapiranja) tipa “od nekoliko na više”, kakva se uobičajeno smatraju problemom redundancije. Drugim riječima, ograničenja definirana ulazom (npr. zadatkom) ne definiraju jednoznačno uzorak izlaza (npr. uzorci rotacije zglobova, mišićne sile, aktivacije motoričkih neurona itd.) na način da postoji više (beskonačan broj, uobičajeno) rješenja. Problem je uočio Bernstein (1935, 1967), smatrajući ga središnjim problemom motoričkog upravljanja: “Na koji način središnji živčani sustav (SŽS) odabire jednoznačna rješenja iz brojnih, naizgled jednakih mogućnosti?” Tradicionalni način shvaćanja problema motoričke redundancije pretpostavljao je da SŽS rabi skup kriterija da bi pronašao jednoznačna rješenja takvih problema. Konkretno, mnoštvo optimizacijskih tehnika uporabljeno je za pristup tim problemima uključujući optimizaciju funkcija troškovi-korist, temeljenu na mehaničkim, psihologijskim i neuropsihologijskim varijablama (vidjeti pregled u Prilutsky, 2000; Osenbaum i sur., 1993; Latash, 1993). Princip obilja Gelfand i Tselin (1966) su usporedili mnoge ele-mente uključene na bilo kojem koraku generiranja pokreta s razredom studenata koji žele sa što manje rada izvršiti zadatak. Uveli su princip minimalnog međudjelovanja da bi opisali takve oblike velikih skupina elemenata. Prema tom načelu svaki element nastoji minimizirati svoje međudjelovanje s ostalima, s upravljačkim dijelom te s okolinom. Drugim riječima, svaki element nastoji minimizirati ulaz koji prima iz svih spomenutih izvora. Taj je princip u novije vrijeme razvijen u princip obilja (Gelfand i Latash, 1998). Prema njemu su problemi motoričke redundancije pogrešno formulirani. Preslikavanja tipa “od nekoliko na više”, tipična za takve probleme, ne bi trebalo gledati kao problem računalne naravi za upravljački sustav, nego pak više kao svojevrsni luksuz koji dozvoljava kombiniranje stabilnog funkcioniranja zadatka uz obavljanje ostalih zadataka i reagiranje na moguće ometajuće utjecaje okoline. Rješavanje problema motoričke redundancije ne uključuje izbor jednoznačnog, optimalnog rješenja, nego prije olakša-vanje čitave obitelji rješenja koje mogu biti jedna-ko uspješne u rješavanju problema. Broj tih obitelji rješenja puno je manji od ukupnog broja mogućih rješenja, što znači da se ipak događa neka vrsta selekcije. Taj pomak od traženja jedinstvenog rješenja prema definiranju pravila kojima se organiziraju obitelji rješenja rezultirao je novim pogledom na motoričke sinergije, paradigmatskim pomakom koji je doveo do izvedbene definicije sinergija i do stvaranja novog računalnog pristupa identifikaciji i kvantifikaciji sinergija. Sinergija - radna definicija Riječ “sinergija” rabila se u studijima ljudskog kretanja, kao i za opis motoričkih poremećaja više od stotinu godina. Općenito, definicija je bila sukladna s grčkim prijevodom “raditi zajedno”. U posljednje vrijeme, međutim, ta je riječ poprimila određenije značenje ukorijenjeno u principu obilja (detalj-no vidjeti u Latash, 2008). Postoje, naime, tri vrste sinergija. Prvo, kada je u zadatak uključen privi-dno redundantni skup elemenata, odabire se srednji uzorak raspodjele koji će karakterizirati prosječni doprinos svakog elementa. Drugo, kada se analizira nekoliko pokušaja izvedbe zadatka, izlazi elemenata mogu kovarirati, što je za zadatak korisno, tj. smanjuje se varijabilnost važne varijable u usporedbi sa situacijom koja bi se mogla očekivati kada kovarijacije ne bi bilo. To se svojstvo ponekad naziva kompenzacijom pogreške ili stabilnošću. Treće, isti skup elemenata može se rabiti za formiranje različitih sinergija, tj. različitih uzoraka kovarijacije koji su povoljni za različite varijable cjelokupnog sustava. To se svojstvo može nazvati stabilnošću. Samo sustavi koji mogu pokazati sva tri svojstva nazivat će se sinergijama. Nema apstraktnih sinergija – one uvijek nešto čine. Sinergija se, prema tomu, definira kao neuralna organizacija skupa elementarnih varijabla s ciljem osiguranja svojevrsnih svojstava stabilnosti (stabilizirati ili destabilizirati) varijable koja je izlaz sustava kao cjeline. Hipoteza neupravljanih ljusaka (UCM – uncontrolled manifold hypothesis) i hijerarhijsko upravljanje Uvedena definicija sinergije zahtijeva kvantitativnu metodu koja bi mogla razlikovati sinergiju od nesinergije, kao i kvantificirati sinergije. Takva je metoda razvijena u sklopu nekontroliranih višeslojnih hipoteza. Ona pretpostavlja da neuralni kontroler djeluje u prostoru elementarnih varijabla i u tom prostoru izabire potprostore koji odgovaraju željenoj vrijednosti uspješno izvedene varijable. Nadalje, kontroler organizira interakcije među elementima tako da je varijanca među elementarnim varijablama uglavnom ograničena UCM-om. Bilo je nekoliko pokušaja da se ponude mehanizmi koji mogu organizirati takvu vrstu kontrole – feedback perifernih senzora, feedback koji koristi uparivanje centralnih i povratnih neuralnih petlji, kontrolni anticipacijski program. Pojam referentne konfiguracije pruža privlačan okvir za analizu motoričkih sinergija. Taj okvir pretpostavlja hijerarhijski kontrolni sustav u kojemu je , na svakom stupnju hijerarhije, taj sustav redundantan, tj. proizvodi puno više izlaznih varijabli od broja ograničenja specificiranih ulaznim varijablama (kao na slici 3). Ostale karakteristike akcije mogu varirati na temelju sekundarnih zakonitosti, koje vjerojatno odražavaju optimizaciju nekih osobina izvedbe. Zato što je sustav redundantan, referentna konfiguracija na višem hijerarhijskom stupnju ne specificira sasvim nedvojbeno sve referentne konfiguracije na nižim stupnjevima. Izranjanje određenih nižerazinskih referentnih trajektorija može se temeljiti na mehanizmu povratne sprege ili na mehanizmu anticipacije (feed-forward). Stoga se hijerarhija kontrolnih razina, gdje svaka razina funkcionira na na-čelu kontrole ravnotežne točke, čini vrlo vjerojatnom strukturom koja podržava motoričke sinergije

Elucidating the genetic basis of antioxidant status in lettuce (Lactuca sativa).

A diet rich in phytonutrients from fruit and vegetables has been acknowledged to afford protection against a range of human diseases, but many of the most popular vegetables are low in phytonutrients. Wild relatives of crops may contain allelic variation for genes determining the concentrations of these beneficial phytonutrients, and therefore understanding the genetic basis of this variation is important for breeding efforts to enhance nutritional quality. In this study, lettuce recombinant inbred lines, generated from a cross between wild and cultivated lettuce (Lactuca serriola and Lactuca sativa, respectively), were analysed for antioxidant (AO) potential and important phytonutrients including carotenoids, chlorophyll and phenolic compounds. When grown in two environments, 96 quantitative trait loci (QTL) were identified for these nutritional traits: 4 for AO potential, 2 for carotenoid content, 3 for total chlorophyll content and 87 for individual phenolic compounds (two per compound on average). Most often, the L. serriola alleles conferred an increase in total AOs and metabolites. Candidate genes underlying these QTL were identified by BLASTn searches; in several cases, these had functions suggesting involvement in phytonutrient biosynthetic pathways. Analysis of a QTL on linkage group 3, which accounted for >30% of the variation in AO potential, revealed several candidate genes encoding multiple MYB transcription factors which regulate flavonoid biosynthesis and flavanone 3-hydroxylase, an enzyme involved in the biosynthesis of the flavonoids quercetin and kaempferol, which are known to have powerful AO activity. Follow-up quantitative RT-PCR of these candidates revealed that 5 out of 10 genes investigated were significantly differentially expressed between the wild and cultivated parents, providing further evidence of their potential involvement in determining the contrasting phenotypes. These results offer exciting opportunities to improve the nutritional content and health benefits of lettuce through marker-assisted breeding

Marine nutrient subsidies promote biogeochemical hotspots in undisturbed, highly humic estuaries

The land-ocean dissolved organic carbon (DOC) flux represents a significant term within the global carbon budget, with peatland-dominated regions representing the most intense sources of terrestrial DOC export. As the interface between freshwater and marine systems, estuaries have the potential to act as a filter of the land-ocean carbon flux, removing terrestrially derived DOC, which is present at low concentrations in the oceans, via a combination of physicochemical and biological processes. However, the fate of peat-derived DOC within estuaries remains poorly quantified, partly due to the complicating influences of heterogeneous soils, land-use, point sources, and upstream modification of organic matter. To minimize these modifying factors, we studied DOC and inorganic nutrients in four small, peat-dominated, minimally disturbed, and oligotrophic Falkland Island estuaries. Contrary to expectations, we found limited evidence of physicochemical estuarine DOC removal, and instead observed apparent "hot zones" of biogeochemical activity, where terrestrially-derived silicate mixed with inorganic nitrogen and phosphorus entering the estuaries from the nutrient-rich marine ecosystem. In two estuaries, this coincided with apparent in situ DOC production. We suggest that the observed phenomena of marine nutrient subsidy of estuarine productivity, and flexible utilization of multiple nutrients within the oligotrophic system, may once have been widespread in temperate estuaries. However, this function has been lost in many ecosystems due to catchment eutrophication by agricultural and urban development. We conclude that the estuaries of the Falkland Islands provide a valuable pre-disturbance analogue for natural biogeochemical functioning in temperate estuaries receiving high organic matter inputs

Application of quality by design tools to upstream processing of platelet precursor cells to enable in vitro manufacture of blood products

Annually 4.5 million platelet units are transfused in Europe and the United States. These are obtained solely from allogeneic donations and have a shelf life of 5-7 days. To address the corresponding supply challenge, Moreau et al.1 devised a novel process for producing megakaryocytes (MKs, the platelet precursor cell) in vitro. A transcription-factor driven, forward-programming (FOP) approach converts human pluripotent stem cells into MKs. This strategy has the unique advantage of generating high yields of pure MKs in chemically defined medium which could lead to the production of a consistent, reliable supply of platelets which overcomes the logistical, financial and biosafety challenges for health organisations worldwide. Here we follow a Quality by Design (QbD) approach to enable improvements to the upstream processing of FOPMKs. Firstly, we created a process flow diagram for production of in vitro platelets for transfusion, which segregated processes into individual unit operations for control and optimisation. Next, we developed a Quality Target Product Profile (QTPP) and identified Critical Quality Attributes (CQAs) for each stage. We conducted a range of experiments utilising Design of Experiments (DOE) and mechanistic modelling2 tools to link Critical Process Parameters (CPPs) to CQAs. For adherent culture, we identified a productivity limit related to surface area available for growth and a cell loss phase which was dependent on cell seeding density, RhoK inhibitor usage and seed density. Using suspension cultures of FOPMK. We noted that TPO and Doxycycline concentration were CPPs as these impacted cell net growth rate and phenotype trajectory. Furthermore, we noted that medium exhaustion led to a 30% loss of viable cells over 8 hours. Proof of concept studies also showed that FOPMKs can be cultured in scaled-down suspension systems (ambr-15 and spinner flask culture) whilst retaining CQAs. 1. Moreau, T. et al. Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming. Nat. Commun. 7, 1–15 (2016). 2. Stacey, A. J., Cheeseman, E. A., Glen, K. E., Moore, R. L. L. & Thomas, R. J. Experimentally integrated dynamic modelling for intuitive optimisation of cell-based processes and manufacture. Biochem. Eng. J. 132, 130–138 (2018)