Advances in cyclin-dependent kinase inhibitors for the treatment of melanoma

Despite the recent advances in the treatment of malignant melanoma with immunotherapy and BRAF/MEK targeted agents, advanced disease still beholds a poor prognosis for a significant proportion of patients. Cyclin dependent kinase (CDK) inhibitors have been investigated as novel melanoma therapeutics throughout a range of phase 1 and 2 trials, as single agents and in combination with established treatments. Areas covered: This article summarises the rationale for, and development of CDK inhibitors in melanoma, with their evolution from pan-CDK inhibitors to highly specific agents, throughout clinical trials and finally their potential future use. Expert opinion: Whilst CDK inhibitors have been practice changing in breast cancer management, their efficacy is yet to be proven in melanoma. Combination with BRAF/MEK inhibitors has been hindered by dose limiting toxicities, but their role may yet to be found within the spectrum of biomarker derived personalised melanoma management. The effect that CDK inhibitors can have as an adjunct to immunotherapy also remains to be seen

Мовні реалії іншого часу і простору (про особливості слововживання у творах Івана Багряного)

The structure of Earthʼs deep inner core has important implications for core evolution, since it is thought to be related to the early stages of core formation. Previous studies have suggested that there exists an innermost inner core with distinct anisotropy relative to the rest of the inner core. Using an extensive new data set of handpicked absolute travel time observations of the inner core phase PKIKP, we find that the data are best explained by variations in anisotropy between two hemispheres and do not require an innermost inner core. We demonstrate that observations of an innermost inner core are an artifact from averaging over lateral anisotropy variations. More significantly we show that hemispherical variations in anisotropy, previously only imaged in the upper inner core, continue to its centre. The eastern region has 0.5–1.5% anisotropy, whereas the western region has 3.5–8.8% anisotropy increasing with depth, with a slow direction at 57–61° to the Earthʼs rotation axis at all depths. Such anisotropy is consistent with models of aligned hcp or bcc iron aggregates

Experiences of pregnant women recieving acupuncture treatment from Midwives

Acupuncture is potentially an effective treatment for common conditions of pregnancy and labour pain with midwives being well placed to offer it. The aims of this study were to explore the experiences of pregnant women receiving acupuncture treatment from midwives, to provide insight into their perceptions of effect including the influence and value of the midwife on this experience. The lack of qualitative evidence has provided the rationale for this study. Within a phenomenological methodology an 'Interpretative Phenomenological Analysis' (IPA) approach was adopted, with 10 women attending the Salford Midwifery Acupuncture Service (SMAS) being recruited to this study. Data was collected via semi-structured interviews and the IPA analysis identified five main themes; justification of choice, relief & relaxation, trust & understanding, regaining self, discovering and sharing a secret. The women were happy to access acupuncture if recommended by a health professional; they gained pain relief and improved function, with more ability to care for their children and to continue working. They were grateful for the opportunity to access acupuncture, finding it enjoyable and reporting intense emotional and physical sensations. It offered prolonged effect, improving sleep and wellbeing, and it correlated well with purported neurophysiological mechanisms. Responses seemed more intense than in previous reports, possibly due to their pregnant state or heightened affective component. A midwife-acupuncturist was advantageous having knowledge and understanding of pregnancy, with ‘understanding’ being more important than professional background. The women felt optimistic and empowered to make plans for birth and parenthood and were wishing to share their experiences with others. The ‘lay network’ was an important factor within the women’s choice to access acupuncture. These findings indicate acupuncture is an acceptable treatment which can provide relief, improved wellbeing and support normality. Midwives could offer acupuncture as an adjunct to their role to facilitate individualised reflexive practice

Partisan Bias Among U.S. Military Service Members and Veterans

Scholars argue that growing partisanship among U.S. military service members and veterans erodes the military’s apolitical social norms and threatens healthy civil-military relations. I investigate this question by examining how service members’ and veterans’ partisan attitudes and apolitical social norms affect their opinions about partisan political activities. In an original survey experiment, military service members and veterans were asked to judge the appropriateness of three political activities which benefitted either their preferred party, the opposing party, or an unspecified party. I find that service members and veterans judge political activities that benefit their preferred party to be more appropriate than activities that benefit the opposing party. Additionally, I find inconclusive evidence that apolitical social norms moderate this effect. These findings suggest that concerns about rising partisanship and political activism in the military may be warranted

The BaSICS (Baby Skin Integrity Comparison Survey) study : a prospective experimental study using maternal observations to report the effect of baby wipes on the incidence of irritant diaper dermatitis in infants, from birth to eight weeks of age

Background Baby wipes have been shown to be safe and effective in maintaining skin integrity when compared to the use of water alone. However, no previous study has compared different formulations of wipe. The aim of the BaSICS study was to identify any differences in incidence of irritant diaper dermatitis (IDD) in infants assigned to three different brands of wipe, all marketed as suitable for neonates, but which contained varying numbers of ingredients. Methods Women were recruited during the prenatal period. Participants were randomly assigned to receive one of three brands of wipe for use during the first eight weeks following childbirth. All participants received the same nappies. Participants reported their infant’s skin integrity on a scale of 1 to 5 daily using a bespoke smartphone application. Analysis of effect of brand on clinically significant IDD (score 3 or more) incidence was conducted using a negative binomial generalised linear model, controlling for possible confounders at baseline. Analysts were blind to brand of wipe. Results Of 737 women enrolled, 15 were excluded (admitted to neonatal intensive care, premature or other infant health issues). Of the 722 eligible babies, 698 (97%) remained in the study for the full 8-week duration, 24.6% of whom had IDD at some point during the study. Mothers using the brand with the fewest ingredients reported fewer days of clinically significant nappy rash (score≥3) than participants using the two other brands (p=0.002 and p<0.001). Severe IDD (grades 4 and 5) was rare (2.4%). Conclusions Rarity of severe IDD suggested that sensitive formula baby wipes are safe when used in cleansing babies from birth to eight weeks during nappy changes. The brand with fewest ingredients had significantly fewer days of clinically significant IDD. Daily observations recorded on a smartphone application proved to be a highly acceptable method of obtaining real-time data on IDD