Editorial of "International Journal of Critical Indigenous Studies, Volume 8, Number 2, 2015"

The articles in this edition address two critical concerns that can be broadly characterised as Indigeneity as a spectacle and the elision of Indigenous sovereignty by multiculturalism and diversity. The first article, by Maryrose Casey, examines nineteenth and early twentieth century Indigenous performances that drew on cultural practices for entertainment. She highlights how these commercially driven performances were, in fact, demonstrations of sovereignty that white colonisers paid to observe. A measure of the success of these demonstrations can be found in the reactions of audiences, which often involved disrupting the spectacle by physically occupying the performance space.

8-13 Hz fluctuations in rectal pressure are an objective marker of clitorally-induced orgasm in women

Orgasm is a subjective experience accompanied by involuntary muscle contractions. We hypothesized that orgasm in women would be distinguishable by frequency analysis of a perineal muscle-derived signal. Rectal pressure, an index of perineal muscle activity, was measured continuously in 23 healthy women during different sexual tasks: receiving clitoral stimulation, imitation of orgasm, and attempt to reach orgasm, in which case the women were asked to report whether orgasm had been reached ("orgasm") or not ("failed orgasm attempt"). We performed spectral analysis on the rectal pressure data and calculated the spectral power in the frequency bands delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), and beta (13-25 Hz). The most significant and most important difference in spectral power between orgasm and both control motor tasks (imitation of orgasm and failed orgasm attempt) was found in the alpha band. An objective rule based on spectral power in the alpha band recognized 94% (29/31) of orgasms and correctly labeled 69% (44/64) of all orgasm attempts as either successful or failed. Because outbursts of alpha fluctuations in rectal pressure only occurred during orgasm and not during voluntary imitation of orgasm or failed attempts, we propose that they represent involuntary contractions of muscles in the rectal vicinity. This is the first objective and quantitative measure that has a strong correspondence with the subjective experience of orgasm.

A shift in priority in diabetic foot care and research: 75% of foot ulcers are preventable

Diabetic foot ulceration poses a heavy burden on the patient and the healthcare system, but prevention thereof receives little attention. For every euro spent on ulcer prevention, ten are spent on ulcer healing, and for every randomized controlled trial conducted on prevention, ten are conducted on healing. In this article, we argue that a shift in priorities is needed. For the prevention of a first foot ulcer, we need more insight into the effect of interventions and practices already applied globally in many settings. This requires systematic recording of interventions and outcomes, and well-designed randomized controlled trials that include analysis of cost-effectiveness. After healing of a foot ulcer, the risk of recurrence is high. For the prevention of a recurrent foot ulcer, home monitoring of foot temperature, pressure-relieving therapeutic footwear, and certain surgical interventions prove to be effective. The median effect size found in a total of 23 studies on these interventions is large, over 60%, and further increases when patients are adherent to treatment. These interventions should be investigated for efficacy as a state-of-the-art integrated foot care approach, where attempts are made to assure treatment adherence. Effect sizes of 75-80% may be expected. If such state-of-the-art integrated foot care is implemented, the majority of problems with foot ulcer recurrence in diabetes can be resolved. It is therefore time to act and to set a new target in diabetic foot care. This target is to reduce foot ulcer incidence with at least 75%.

Measuring the multidimensions of symptoms in people with advanced stages of chronic kidney disease

Chronic kidney disease (CKD) is increasing globally and in Saudi Arabia it affects approximately 8% annual increment of dialysis population. It is associated with a high symptom burden. Previous studies have largely reported on the prevalence of symptoms only in the haemodialysis population. This study examined symptom burden across disease stages and treatment groups in advanced CKD, and their correlation with demographic and clinical factors. Using a cross-sectional design, a convenience sample of 436 patients with CKD was recruited from three hospitals in Saudi Arabia. The CKD Symptom Burden Index (CKD-SBI) was used to measure 32 CKD symptoms. Demographic and clinical data were also collected. Of the sample 75.5% were receiving dialysis (haemodialysis, n = 287; peritoneal dialysis, n = 42) and 24.5% were non-dialysis (CKD stage 4, n = 69; CKD stage 5, n = 38). Average symptom reported was 13.01 ± 7.67. Fatigue and pain were common and burdensome across all symptom dimensions.Approximately one-third of participants experienced sexual symptoms. Dialysis patients reported greater symptom burden, especially patients on haemodialysis. Haemodialysis treatment, older age and being female were independently associated with greater total symptom burden. In conclusion, symptom burden is high among advanced stages of CKD, particularly among those receiving dialysis. Although fatigue, pain and sexual dysfunction are key contributors to symptom burden in CKD, these symptoms are often under-recognised and warrant routine assessment. The CKD-SBI offers a valuable tool to assess symptom burden, leading to the commencement of timely and appropriate interventions.

Molecular dynamics simulations of CXCL-8 and its interactions with a receptor peptide, heparin fragments, and sulfated linked cyclitols

CXCL-8 (Interleukin 8) is a CXC chemokine with a central role in the human immune response. We have undertaken extensive in silico analyses to elucidate the interactions of CXCL-8 with its various binding partners, which are crucial for its biological function. Sequence and structure analyses showed that residues in the thirdq β-sheet and basic residues in the heparin binding site are highly variable, while residues in the second β-sheet are highly conserved. Molecular dynamics simulations in aqueous solution of dimeric CXCL-8 have been performed with starting geometries from both X-ray and NMR structures showed shearing movements between the two antiparallel C-terminal helices. Dynamic conservation analyses of these simulations agreed with experimental data indicating that structural differences between the two structures at quaternary level arise from changes in the secondary structure of the N-terminal loop, the 310-helix, the 30s, 40s, and 50s loops and the third β-sheet, resulting in a different interhelical separation. Nevertheless, the observation of these different states indicates that CXCL-8 has the potential to undergo conformational changes, and it seems likely that this feature is relevant to the mode of binding of glycosaminoglycan (GAG) mimetics such as cyclitols. Simulations of the receptor peptide fragment−CXCL-8 complex identified several specific interactions of the receptor peptide with CXCL-8 that could be exploited in the structure-based design of competitive peptides and nonpeptidic molecules targeting CXCL-8 for combating inflammatory diseases. Simulations of the CXCL-8 dimer complexed with a 24-mer heparin fragment and of the CXCL-8−receptor peptide complex revealed that Arg60, Lys64, and Arg68 in the dimer bind to cyclitols in a horseshoe pattern, defining a region which is spatially distinct from the receptor binding site. There appears to be an optimum number of sulfates and an optimum length of alkyl spacers required for the interaction of cyclitol inhibitors with the dimeric form of CXCL-8. Calculation of the binding affinities of cyclitol inhibitors reflected satisfactorily the ranking of experimentally determined inhibitory potencies. The findings of these molecular modeling studies will help in the search for inhibitors which can modulate various CXCL-8 biological activities and serve as an excellent model system to study CXC-inhibitor interactions.

Social determinants of health and diabetic foot disease

Background Diabetic foot disease (DFD) is the leading cause of hospitalisation and lower extremity amputation (LEA) in people with diabetes. Many studies have established the relationship between DFD and clinical risk factors, such as peripheral neuropathy and peripheral arterial disease. Other studies have identified the relationship between diabetes and non-clinical risk factors termed social determinants of health (SDoH), such as socioeconomic status. However, it appears very few studies have investigated the relationship between DFD and SDoH. This paper aims to review the existing literature investigating the relationship between DFD and the SDoH factors socioeconomic status (SES), race and geographical remoteness (remoteness). Process Electronic databases (MEDLINE, CINAHL, and PubMed) were searched for studies reporting SES, race (including Aboriginal and Torres Strait Islander in Australia) and remoteness and their relationship to DFD and LEA. Exclusion criteria were studies conducted in developing countries and studies published prior to 2000. Findings Forty-eight studies met the inclusion criteria and were reviewed; 10 in Australia. Overall, 28 (58%) studies investigated LEA, 10 (21%) DFD, and 10 (21%) DFD and LEA as the DFD-related outcome. Thirty-six (75%) studies investigated the SDoH risk factor of race, 22 (46%) SES, and 20 (42%) remoteness. SES, race and remoteness were found to be individually associated with LEA and DFD in the majority of studies. Only four studies investigated interactions between SES, race and remoteness and DFD with contrasting findings. All four studies used only LEA as their investigated outcome. No Australian studies investigate the interaction of all three SDoH risk factors on DFD outcomes. Conclusions The SDoH risk factors of SES, race and GR appear to be individually associated with DFD. However, only few studies investigated the interaction of these three major SDoH risk factors and DFD outcomes with contrasting results. There is a clear gap in this area of DFD research and particularly in Australia. Until urgent future research is performed, current practice and policy does not adequately take into consideration the implication of SDoH on DFD.

Prediction of individual genetic risk to prostate cancer using a polygenic score

BACKGROUND Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate cancer risk at a genome-wide significant level will improve disease prediction. METHODS We built polygenic risk scores in a large training set comprising over 25,000 individuals. Initially 65 established prostate cancer susceptibility variants were selected. After LD pruning additional variants were prioritized based on their association with prostate cancer. Six-fold cross validation was performed to assess genetic risk scores and optimize the number of additional variants to be included. The final model was evaluated in an independent study population including 1,370 cases and 1,239 controls. RESULTS The polygenic risk score with 65 established susceptibility variants provided an area under the curve (AUC) of 0.67. Adding an additional 68 novel variants significantly increased the AUC to 0.68 (P = 0.0012) and the net reclassification index with 0.21 (P = 8.5E-08). All novel variants were located in genomic regions established as associated with prostate cancer risk. CONCLUSIONS Inclusion of additional genetic variants from established prostate cancer susceptibility regions improves disease prediction. Prostate 75:1467–1474, 2015. © 2015 Wiley Periodicals, Inc.

3D hierarchical rutile TiO2 and metal-free organic sensitizer producing dye-sensitized solar cells 8.6% conversion efficiency

Three-dimensional (3D) hierarchical nanoscale architectures comprised of building blocks, with specifically engineered morphologies, are expected to play important roles in the fabrication of 'next generation' microelectronic and optoelectronic devices due to their high surface-to-volume ratio as well as opto-electronic properties. Herein, a series of well-defined 3D hierarchical rutile TiO2 architectures (HRT) were successfully prepared using a facile hydrothermal method without any surfactant or template, simply by changing the concentration of hydrochloric acid used in the synthesis. The production of these materials provides, to the best of our knowledge, the first identified example of a ledgewise growth mechanism in a rutile TiO2 structure. Also for the first time, a Dye-sensitized Solar Cell (DSC) combining a HRT is reported in conjunction with a high-extinction-coefficient metal-free organic sensitizer (D149), achieving a conversion efficiency of 5.5%, which is superior to ones employing P25 (4.5%), comparable to state-of-the-art commercial transparent titania anatase paste (5.8%). Further to this, an overall conversion efficiency 8.6% was achieved when HRT was used as the light scattering layer, a considerable improvement over the commercial transparent/reflector titania anatase paste (7.6%), a significantly smaller gap in performance than has been seen previously.