Geometric View of Measurement Errors

The slope of the best fit line from minimizing the sum of the squared oblique errors is the root of a polynomial of degree four. This geometric view of measurement errors is used to give insight into the performance of various slope estimators for the measurement error model including an adjusted fourth moment estimator introduced by Gillard and Iles (2005) to remove the jump discontinuity in the estimator of Copas (1972). The polynomial of degree four is associated with a minimun deviation estimator. A simulation study compares these estimators showing improvement in bias and mean squared error

Compassion in Practice – evaluating the awareness, involvement and perceived impact of a national nursing and midwifery strategy amongst health care professionals in NHS Trusts in England

Aim: To report the findings from an evaluation of the impact of the Compassion in Practice Vision & Strategy (CiPVS) (National Health Service England (NHSE), 2012) on nursing, midwifery and care staff. Background: The CiPVS was a programme of work to highlight the importance of compassionate care following the Francis Report in 2013 into the deficits in care in an NHS hospital trust. It was launched by NHS England in 2012 at a time when fiscal cuts were introduced by the Department of Health in England. Design and setting: Mixed methods. Results: Inferential statistics were used to test whether there were significant differences between staff at different levels of seniority with regard to awareness and involvement in CiPVS and their attitudes to it. Awareness and involvement of staff in CiPVS was high amongst middle and senior management but limited at ward level. Staff were not involved in CiPVS due to a lack of awareness. Ward level staff who were aware and involved perceived a lack of support and communication from senior leadership to deliver CiPVS. Discussion: Results reveal professional anger, distress and resistance to CiPVS and a view of the programme as a top down initiative which did not sufficiently recognise structural constraints on nurses’ ability to deliver compassionate care. We discuss the implications of our findings for global nursing. Conclusion: Participants emphasised that compassion for patients is only sustainable where there is compassion for staff and many participants felt that they were not being treated with compassion. Relevance for practice: NHSE should strongly affirm that nurses and midwives in general provide compassionate care. Trust leadership should provide support for ward level staff who deliver compassionate care in difficult circumstances

Continuous cardiac autonomic and haemodynamic responses to isometric exercise in females

Purpose: Hypertension is associated with impaired haemodynamic control mechanisms and autonomic dysfunction. Isometric exercise (IE) interventions have been shown to improve autonomic modulation and reduce blood pressure (BP) in predominantly male participants. The physiological responses to IE are under explored in female populations; therefore, this study investigated the continuous cardiac autonomic and haemodynamic response to a single bout of IE in a large female population. Methods: Forty physically inactive females performed a single, individually prescribed isometric wall squat training session. Total power spectral density of heart rate variability (HRV) and associated low frequency (LF) and high-frequency (HF) power spectral components, were recorded in absolute (ms2) and normalised units (nu) pre, during and post an IE session. Heart rate (HR) was recorded via electrocardiography and baroreceptor reflex sensitivity (BRS) via the sequence method. Continuous blood pressure was recorded via the vascular unloading technique and stroke volume via impedance cardiography. Total peripheral resistance (TPR) was calculated according to Ohm’s Law. Results: During IE, there were significant reductions in HRV (p<0.001) and BRS (p<0.001), and significant increases in heart rate (p<0.001), systolic, mean and diastolic BP (p<0.001 for all). In recovery following the IE session, cardiac autonomic parameters returned to baseline (p=0.974); however, total peripheral vascular resistance significantly reduced below baseline (p<0.001). This peripheral vascular response was associated with significant reductions in systolic (-17.3±16.5 mmHg, p<0.001), mean (-18.8±17.4 mmHg, p<0.001) and diastolic BP (-17.3±16.2 mmHg, p<0.001), below baseline. Conclusion: A single IE session is associated with improved haemodynamic cardiovascular responses in females. Cardiac autonomic responses return to baseline values, which suggests alternative mechanisms are responsible for the post exercise haemodynamic improvements in females. Future mechanistic research is required to investigate the acute and chronic effects of IE in female populations with different resting BP profiles

Prion aggregate structure in yeast cells is determined by the Hsp104-Hsp110 disaggregase machinery

Prions consist of misfolded proteins that have adopted an infectious amyloid conformation. In vivo, prion biogenesis is intimately associated with the protein quality control machinery. Using electron tomography, we probed the effects of the heat shock protein Hsp70 chaperone system on the structure of a model yeast [PSI+] prion in situ. Individual Hsp70 deletions shift the balance between fibril assembly and disassembly, resulting in a variable shell of nonfibrillar, but still immobile, aggregates at the surface of the [PSI+] prion deposits. Both Hsp104 (an Hsp100 disaggregase) and Sse1 (the major yeast form of Hsp110) were localized to this surface shell of [PSI+] deposits in the deletion mutants. Elevation of Hsp104 expression promoted the appearance of this novel, nonfibrillar form of the prion aggregate. Moreover, Sse1 was found to regulate prion fibril length. Our studies reveal a key role for Sse1 (Hsp110), in cooperation with Hsp104, in regulating the length and assembly state of [PSI+] prion fibrils in vivo

The safety of isometric exercise: rethinking the exercise prescription paradigm for those with stage 1 hypertension.

Few studies have investigated the relative safety of prescribing isometric exercise (IE) to reduce resting blood pressure (BP). This study aimed to ascertain the safety of the hemodynamic response during an IE wall squat protocol.Twenty-six hypertensive (BP of 120-139 mm Hg systolic and/or 80-90 mm Hg diastolic) males (45 ± 8 years; 1.78 ± 0.07 m; 89.7 ± 12.3 kg; mean ± SD), visited the laboratory on 2 separate occasions. Heart rate (HR) and BP were measured at rest and continuously throughout exercise. In visit 1, participants completed a continuous incremental isometric wall squat exercise test, starting at 135° of knee flexion, decreasing by 10° every 2 minutes until 95° (final stage). Exercise was terminated upon completion of the test or volitional fatigue. The relationship between knee joint angle and mean HR was used to calculate the participant-specific knee joint angle required to elicit a target HR of 95% HRpeak. This angle was used to determine exercise intensity for a wall squat training session consisting of 4 × 2 minute bouts (visit 2).Systolic BPs during the exercise test and training were 173 ± 21 mm Hg and 171 ± 19 mm Hg, respectively, (P > .05) and were positively related (r = 0.73, P  .05) and were positively related (r = 0.42, P  250 mm Hg. Diastolic BP values > 115 mm Hg were recorded in 12 participants during the incremental test and 6 participants during the training session. Peak rate pressure product was 20681 ± 3911 mm Hg bpm during the IE test and was lower (18074 ± 3209 mm Hg bpm) during the IE session (P = .002). No adverse effects were reported.Based on the current ACSM guidelines for aerobic exercise termination, systolic BP does not reach the upper limit during IE in this population. Diastolic BP exceeds 115 mm Hg in some during the IE protocol, which may suggest the need to individualise IE training prescription in some with suboptimal BP control. Future research is required to ascertain if IE requires modified BP termination guidelines

Neurohumoral and ambulatory haemodynamic adaptations following isometric exercise training in unmedicated hypertensive patients

Objective: Hypertension remains the leading modifiable risk factor for cardiovascular disease (CVD). Isometric exercise training (IET) has been shown to be a useful non-pharmacological intervention for reducing resting blood pressure (BP). This study aimed to measure alterations in office BP, ambulatory BP, cardiac autonomic modulation and inflammatory and vascular biomarkers following a programme of IET in unmedicated hypertensive patients. Methods: Twenty-four unmedicated stage 1 hypertensive patients (age 43.8±7.3 years; height, 178.1±7 cm; weight 89.7±12.8 kg) were randomly assigned in a cross-over study design, to 4-weeks of home based IET and control period, separated by a 3-week washout period. Office and Ambulatory BP, cardiac autonomic modulation, and inflammatory and vascular biomarkers were recorded pre and post IET and control periods. Results: Clinic and 24-hour ambulatory BP significantly reduced following IET by 12.4/6.2 mmHg and 11.8/5.6 mmHg in systolic/diastolic BP, respectively (p<0.001 for both), compared to the control. The BP adaptations were associated with a significant (p=0.018) reduction in the average real variability of 24-hour ambulatory BP following IET, compared to control. Cardiac autonomic modulation improved by 11% (p<0.001), baroreceptor reflex sensitivity improved by 47% (p<0.001), and interleukin-6 and asymmetric dimethylarginine reduced by 10% (p=0.022) and 19% (p=0.023), respectively, which differed significantly to the control period. Conclusion: This is the first evidence of durable BP reduction and wider CVD risk benefits of IET in a relevant patient population. Our findings support the role of IET as a safe and viable therapeutic and preventative intervention in the treatment of HTN