Investigating the effects of artificial baroreflex stimulation on pain perception: A comparative study in no-pain and chronic low back pain individuals.

The autonomic nervous system (ANS) and pain exhibit a reciprocal relationship, where acute pain triggers ANS responses, whereas resting ANS activity can influence pain perception. Nociceptive signalling can also be altered by 'top-down' processes occurring in the brain, brainstem and spinal cord, known as 'descending modulation'. By employing the conditioned pain modulation (CPM) paradigm, we previously revealed a connection between reduced low-frequency heart rate variability and CPM. Individuals with chronic pain often experience both ANS dysregulation and impaired CPM. Baroreceptors, which contribute to blood pressure and heart rate variability regulation, may play a significant role in this relationship, although their involvement in pain perception and their functioning in chronic pain have not been sufficiently explored. In the present study, we combined artificial 'baroreceptor stimulation' in both pressure pain and CPM paradigms, seeking to explore the role of baroreceptors in pain perception and descending modulation. In total, 22 individuals with chronic low back pain (CLBP) and 29 individuals with no-pain (NP) took part in the present study. We identified a differential modulation of baroreceptor stimulation on pressure pain between the groups of NP and CLBP participants. Specifically, NP participants perceived less pain in response to baroreflex activation, whereas CLBP participants exhibited increased pain sensitivity. CPM scores were associated with baseline measures of baroreflex sensitivity in both CLBP and NP participants. Our data support the importance of the baroreflex in chronic pain and a possible mechanism of dysregulation involving the interaction between the ANS and descending pain modulation. KEY POINTS: Baroreflex stimulation has different effects on pressure pain in participants with chronic pain compared to matched individuals with no-pain. Baroreceptor activation decreases pain in participants with no-pain but increases pain perception in participants with chronic pain. Baroreflex sensitivity is associated with conditioned pain modulation in both groups of chronic pain and no-pain participants. The reactivity of the baroreflex during autonomic stress demonstrated a positive correlation with Pain Trait scores in participants with chronic back pain.

A shedding analysis after AAV8 CNS injection revealed fragmented viral DNA without evidence of functional AAV particles in mice.

Adeno-associated viruses (AAV) are commonly used in the scientific field due to their diverse application range. However, AAV shedding, the release of virions from the host organism, can impact the safety of AAV-based approaches. An increasing number of authorities require the characterization of vector shedding in clinical trials. Recently, shedding of transduced laboratory animals has also gained attention regarding the necessary disposal measures of their waste products. However, no explicit international regulations for AAV-shedding waste exist. Generating insights into shedding dynamics becomes increasingly relevant to help authorities develop adequate regulations. To date, knowledge of AAV vector shedding in mice is very limited. Moreover, confirmation of functional shed AAV particles in mice is missing. Therefore, we examined feces, urine, and saliva of mice after CNS injection with AAV2/8. It revealed the presence of viral DNA fragments via qPCR for up to 4 days after injection. To examine AAV functionality we performed nested PCR and could not detect full-length viral genomes in any but two collected feces samples. Furthermore, a functional infection assay did not reveal evidence of intact AAV particles. Our findings are supposed to contribute murine shedding data as a foundation to help establish still lacking adequate biosafety regulations in the context of AAV shedding.

Correction: Creatively Adapting Touch-Based Practices to the Web Format During the COVID-19 Pandemic: Systematic Review.

[This corrects the article DOI: 10.2196/46355.].

Loss of parkin causes endoplasmic reticulum calcium dyshomeostasis by upregulation of reticulocalbin 1.

Increasing evidence suggests that astrocytes play an important role in the progression of Parkinson's disease (PD). Previous studies on our parkin knockout mouse demonstrated a higher accumulation of damaged mitochondria in astrocytes than in surrounding dopaminergic (DA) neurons, suggesting that Parkin plays a crucial role regarding their interaction during PD pathogenesis. In the current study, we examined primary mesencephalic astrocytes and neurons in a direct co-culture system and discovered that the parkin deletion causes an impaired differentiation of mesencephalic neurons. This effect required the parkin mutation in astrocytes as well as in neurons. In Valinomycin-treated parkin-deficient astrocytes, ubiquitination of Mitofusin 2 was abolished, whereas there was no significant degradation of the outer mitochondrial membrane protein Tom70. This result may explain the accumulation of damaged mitochondria in parkin-deficient astrocytes. We examined differential gene expression in the substantia nigra region of our parkin-KO mouse by RNA sequencing and identified an upregulation of the endoplasmic reticulum (ER) Ca2+ -binding protein reticulocalbin 1 (RCN1) expression, which was validated using qPCR. Immunostaining of the SN brain region revealed RCN1 expression mainly in astrocytes. Our subcellular fractionation of brain extract has shown that RCN1 is located in the ER and in mitochondria-associated membranes (MAM). Moreover, a loss of Parkin function reduced ATP-stimulated calcium-release in ER mesencephalic astrocytes that could be attenuated by siRNA-mediated RCN1 knockdown. Our results indicate that RCN1 plays an important role in ER-associated calcium dyshomeostasis caused by the loss of Parkin function in mesencephalic astrocytes, thereby highlighting the relevance of astrocyte function in PD pathomechanisms.

Single-pulse, reference-free, spatiotemporal characterization of ultrafast laser pulse beams via broadband ptychography.

Ultrafast laser pulse beams are four-dimensional, space-time phenomena that can exhibit complicated, coupled spatial and temporal profiles. Tailoring the spatiotemporal profile of an ultrafast pulse beam is necessary to optimize the focused intensity and to engineer exotic spatiotemporally shaped pulse beams. Here we demonstrate a single-pulse, reference-free spatiotemporal characterization technique based on two colocated synchronized measurements: (1) broadband single-shot ptychography and (2) single-shot frequency resolved optical gating. We apply the technique to measure the nonlinear propagation of an ultrafast pulse beam through a fused silica window. Our spatiotemporal characterization method represents a major contribution to the growing field of spatiotemporally engineered ultrafast laser pulse beams.

Using an interactive nutrition technology platform to predict malnutrition risk.

BACKGROUND: The Nutrition Dashboard is an interactive nutrition technology platform that displays food provision and intake data used to categorise the nutrition risk of hospitalised individuals. The present study aimed to investigate the Nutrition Dashboard's ability to identify malnutrition compared with a validated malnutrition screening tool (MST). METHODS: A retrospective observational study at a 99-bed hospital was conducted using medical record and food intake data presented via the Nutrition Dashboard. Inter-Rater Reliability of food intake estimation between hospital catering staff and a dietitian reported good agreement across 912 food items (κ = 0.69, 95% confidence interval = 0.65-0.72, p < 0.001). Default nutritional adequacy thresholds of 4500 kJ and 50 g protein were applied for Nutrition Dashboard categorisation of supply and intake. Generalised estimating equation regression models explored the association between the Nutrition Dashboard risk categories and the MST, with and without controlling for patient demographic characteristics. RESULTS: Analyses from 216 individuals (1783 hospital-stay days) found that those in the highest risk Nutrition Dashboard category were 1.93 times more likely to have a MST score indicating risk compared to the lowest Nutrition Dashboard category (unadjusted odds ratio = 1.93, 95% confidence interval = 1.17-3.19, p < 0.01). When patient weight was added to the model, lower weight became the only significant predictor of MST ≥ 2 (p < 0.01) CONCLUSIONS: The present study indicates a role for nutrition intake technology in malnutrition screening. Further adaptions that address the complexities of applying this technology could improve the use of the Nutrition Dashboard to support identification of malnutrition.

Creatively Adapting Touch-Based Practices to the Web Format During the COVID-19 Pandemic: Systematic Review.

BACKGROUND: The COVID-19 pandemic forced numerous touch-based fields, including manual therapy, body psychotherapy, arts therapy, creative arts practices, and the fitness industry, to swiftly transition to web-based service delivery. These disciplines faced substantial challenges in adapting their traditionally in-person practices, which rely heavily on physical touch and close proximity, to a web format. OBJECTIVE: This review intends to provide a systematically sourced overview of the literature concerning innovative approaches for adapting touch-based practices to the web format in response to the COVID-19 pandemic. METHODS: A systematic search across 7 databases and gray literature sources identified studies presenting innovative web delivery methods, particularly those addressing the challenges arising from the absence of physical proximity and touch. The inclusion criteria were designed to encompass studies exploring the creative adaptation of touch-based practices to web formats in response to the COVID-19 pandemic irrespective of study methodology. The exclusion criteria applied to studies focusing solely on technical aspects of web delivery or nontouch or noninteractive practices. There were no geographical restrictions, but the selection was limited to publications from 2020 onward. As only qualitative studies were found, data synthesis was conducted thematically. RESULTS: The review encompassed 17 studies revealing that touch-based fields successfully devised innovative and creative methods for web service delivery. These methods were categorized into five main themes: (1) adapted working methods (cross-field methods), (2) adapted working methods for sensorial experiences and nonphysical connections, (3) creative methods using materials or additional tools, (4) creative use of web-based platform tools or additional technologies, and (5) creative methods requiring previous preparation of practitioners or participants. These creative approaches allowed practitioners to address the challenges of web touch-based practices, fostering connections and offering unique sensory experiences, albeit with some concerns related to technology and preparation. CONCLUSIONS: These innovative methods demonstrate promise in circumventing the limitations imposed by the lack of physical touch and proximity in web settings during the COVID-19 pandemic. Furthermore, these insights hold potential for application in other fields in the future. This systematic search and thematic synthesis provide valuable guidance for practitioners and educators seeking to navigate the evolving landscape of web service delivery in touch-based disciplines, ensuring continuity of care even in challenging circumstances. TRIAL REGISTRATION: PROSPERO CRD42022379731; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=379731.

Propionate attenuates atherosclerosis by immune-dependent regulation of intestinal cholesterol metabolism.

AIMS: Atherosclerotic cardiovascular disease (ACVD) is a major cause of mortality and morbidity worldwide, and increased low-density lipoproteins (LDLs) play a critical role in development and progression of atherosclerosis. Here, we examined for the first time gut immunomodulatory effects of the microbiota-derived metabolite propionic acid (PA) on intestinal cholesterol metabolism. METHODS AND RESULTS: Using both human and animal model studies, we demonstrate that treatment with PA reduces blood total and LDL cholesterol levels. In apolipoprotein E-/- (Apoe-/-) mice fed a high-fat diet (HFD), PA reduced intestinal cholesterol absorption and aortic atherosclerotic lesion area. Further, PA increased regulatory T-cell numbers and interleukin (IL)-10 levels in the intestinal microenvironment, which in turn suppressed the expression of Niemann-Pick C1-like 1 (Npc1l1), a major intestinal cholesterol transporter. Blockade of IL-10 receptor signalling attenuated the PA-related reduction in total and LDL cholesterol and augmented atherosclerotic lesion severity in the HFD-fed Apoe-/- mice. To translate these preclinical findings to humans, we conducted a randomized, double-blinded, placebo-controlled human study (clinical trial no. NCT03590496). Oral supplementation with 500 mg of PA twice daily over the course of 8 weeks significantly reduced LDL [-15.9 mg/dL (-8.1%) vs. -1.6 mg/dL (-0.5%), P = 0.016], total [-19.6 mg/dL (-7.3%) vs. -5.3 mg/dL (-1.7%), P = 0.014] and non-high-density lipoprotein cholesterol levels [PA vs. placebo: -18.9 mg/dL (-9.1%) vs. -0.6 mg/dL (-0.5%), P = 0.002] in subjects with elevated baseline LDL cholesterol levels. CONCLUSION: Our findings reveal a novel immune-mediated pathway linking the gut microbiota-derived metabolite PA with intestinal Npc1l1 expression and cholesterol homeostasis. The results highlight the gut immune system as a potential therapeutic target to control dyslipidaemia that may introduce a new avenue for prevention of ACVDs.

[Remote management of musculoskeletal pain : A pragmatic approach to the implementation of video and phone consultations in musculoskeletal practice. German version]. / Telemedizinisches Schmerzmanagement von muskuloskeletalem Schmerz : Ein pragmatischer Ansatz zur Implementierung von Video- und Telefonsprechstunden in der muskuloskeletalen Schmerztherapie. Deutsche Fassung.

INTRODUCTION: Remote consultations through phone or video are gaining in importance for the treatment of musculoskeletal pain across a range of health care providers. However, there is a plethora of technical options for practitioners to choose from, and there are various challenges in the adaptation of clinical processes as well as several special considerations regarding regulatory context and patient management. Practitioners are faced with a lack of high-quality peer-reviewed resources to guide the planning and practical implementation of remote consultations. OBJECTIVES: This Clinical Update seeks to provide practical guidance for the planning and implementation of remote consultations for the management and treatment of people with musculoskeletal pain. METHODS: Recommendations are based on a brief overview of the relevant research regarding phone and video consultations for musculoskeletal practice and derived from the literature, relevant guidelines, and practical experience. RESULTS: The technical feasibility of remote consultations for musculoskeletal complaints is good, patient satisfaction is high, and a growing body of evidence supports its comparative effectiveness to in-person consultations in some circumstances for improving pain and functioning. We consider in detail practical aspects such as the choosing of hardware and software, we touch on the legal and regulatory context, and we focus on the adaptation of clinical processes and communication. CONCLUSION: This Clinical Update draws together best-practice evidence in a practically applicable format, enabling therapists who are working with people with pain to directly apply this knowledge to their individual clinical settings and the requirements of their patients.

Long-term joint outcomes in adolescents with moderate or severe haemophilia A.

INTRODUCTION: Favourable joint outcomes are expected with modern haemophilia A (HA) management. Evaluation of long-term treatment outcomes is hampered by the delay between bleeding episodes during childhood and resulting joint outcomes in adulthood. AIM: To measure the long-term joint health of adolescents with moderate and severe HA, according to severity and inhibitor status. METHODS: Pilot cross-sectional study of five European PedNet centres in moderate and severe HA patients aged 10-19 years. Structured assessment of joint status by physical examination (HJHS) and ultrasound (HEAD-US). RESULTS: In total, 141 HA patients were evaluable, 100 without inhibitors (81 severe, 19 moderate HA), and 41 severe HA with current/past inhibitors. On physical examination, 12/81 (15%) of severe HA without inhibitors, 3/19 (16%) of moderate HA, and 13/41 (32%) of severe HA patients with inhibitors exhibited joint abnormalities. Inhibitor persistence, longer inhibitor duration, and a high peak inhibitor level were associated with impaired joint health. Ultrasound showed joint damage (bone or cartilage) in 13/49 (27%) of severe HA without inhibitors, 1/12 (8%) of moderate HA, and 10/28 (36%) of severe HA patients with inhibitors. A discordant ankle evaluation by ultrasound versus physical examination was present in 53/169 joints (31%). CONCLUSIONS: Most adolescents with severe or moderate HA show favourable joint health. Future research with combined ultrasound and/or MRI is needed to better understand joint outcomes in the remaining patients. Patents with inhibitors showed a two-fold increased proportion with joint deterioration. Ultrasound paired with physical examination increases sensitivity for detection of joint damage.

The association between pain-induced autonomic reactivity and descending pain control is mediated by the periaqueductal grey.

There is a strict interaction between the autonomic nervous system (ANS) and pain, which might involve descending pain modulatory mechanisms. The periaqueductal grey (PAG) is involved both in descending pain modulation and ANS, but its role in mediating this relationship has not yet been explored. Here, we sought to determine brain regions mediating ANS and descending pain control associations. Thirty participants underwent conditioned pain modulation (CPM) assessments, in which they rated painful pressure stimuli applied to their thumbnail, either alone or with a painful cold contralateral stimulation. Differences in pain ratings between 'pressure-only' and 'pressure + cold' stimuli provided a measure of descending pain control. In 18 of the 30 participants, structural scans and two functional MRI assessments, one pain-free and one during cold-pain were acquired. Heart rate variability (HRV) was simultaneously recorded. Normalised low-frequency HRV (LF-HRVnu) and the CPM score were negatively correlated; individuals with higher LF-HRVnu during pain reported reductions in pain during CPM. PAG-ventro-medial prefrontal cortex (vmPFC) and PAG-rostral ventromedial medulla (RVM) functional connectivity correlated negatively with the CPM. Importantly, PAG-vmPFC functional connectivity mediated the strength of the LF-HRVnu-CPM association. CPM response magnitude was also negatively correlated with vmPFC GM volume. Our multi-modal approach, using behavioural, physiological and MRI measures, provides important new evidence of interactions between ANS and descending pain mechanisms. ANS dysregulation and dysfunctional descending pain modulation are characteristics of chronic pain. We suggest that further investigation of body-brain interactions in chronic pain patients may catalyse the development of new treatments. KEY POINTS: Heart rate variability (HRV) is associated with descending pain modulation as measured by the conditioned pain modulation protocol (CPM). There is an association between CPM scores and the functional connectivity between the periaqueductal grey (PAG) and ventro-medial prefrontal cortex (vmPFC). CPM scores are also associated with vmPFC grey matter volume. The strength of functional connectivity between the PAG and vmPFC mediates the association between HRV and CPM. Our data provide new evidence of interactions between the autonomic nervous system and descending pain mechanisms.

Multi-mode root preserving ptychographic phase retrieval algorithm for dispersion scan.

We present a phase retrieval algorithm for dispersion scan (d-scan), inspired by ptychography, which is capable of characterizing multiple mutually-incoherent ultrafast pulses (or modes) in a pulse train simultaneously from a single d-scan trace. In addition, a form of Newton's method is employed as a solution to the square root problem commonly encountered in second harmonic pulse measurement techniques. Simulated and experimental phase retrievals of both single-mode and multi-mode d-scan traces are shown to demonstrate the accuracy and robustness of the root preserving ptychographic algorithm (RPPA).

Spatiospectral characterization of ultrafast pulse-beams by multiplexed broadband ptychography.

Ultrafast pulse-beam characterization is critical for diverse scientific and industrial applications from micromachining to generating the highest intensity laser pulses. The four-dimensional structure of a pulse-beam, E~(x,y,z,ω), can be fully characterized by coupling spatiospectral metrology with spectral phase measurement. When temporal pulse dynamics are not of primary interest, spatiospectral characterization of a pulse-beam provides crucial information even without spectral phase. Here we demonstrate spatiospectral characterization of pulse-beams via multiplexed broadband ptychography. The complex spatial profiles of multiple spectral components, E~(x,y,ω), from modelocked Ti:sapphire and from extreme ultra-violet pulse-beams are reconstructed with minimum intervening optics and no refocusing. Critically, our technique does not require spectral filters, interferometers, or reference pulses.

[Ni(NHC)2 ] as a Scaffold for Structurally Characterized trans [H-Ni-PR2 ] and trans [R2 P-Ni-PR2 ] Complexes.

The addition of PPh2 H, PPhMeH, PPhH2 , P(para-Tol)H2 , PMesH2 and PH3 to the two-coordinate Ni0 N-heterocyclic carbene species [Ni(NHC)2 ] (NHC=IiPr2 , IMe4 , IEt2 Me2 ) affords a series of mononuclear, terminal phosphido nickel complexes. Structural characterisation of nine of these compounds shows that they have unusual trans [H-Ni-PR2 ] or novel trans [R2 P-Ni-PR2 ] geometries. The bis-phosphido complexes are more accessible when smaller NHCs (IMe4 >IEt2 Me2 >IiPr2 ) and phosphines are employed. P-P activation of the diphosphines R2 P-PR2 (R2 =Ph2 , PhMe) provides an alternative route to some of the [Ni(NHC)2 (PR2 )2 ] complexes. DFT calculations capture these trends with P-H bond activation proceeding from unconventional phosphine adducts in which the H substituent bridges the Ni-P bond. P-P bond activation from [Ni(NHC)2 (Ph2 P-PPh2 )] adducts proceeds with computed barriers below 10 kcal mol-1 . The ability of the [Ni(NHC)2 ] moiety to afford isolable terminal phosphido products reflects the stability of the Ni-NHC bond that prevents ligand dissociation and onward reaction.

The Integrator complex regulates differential snRNA processing and fate of adult stem cells in the highly regenerative planarian Schmidtea mediterranea.

In multicellular organisms, cell type diversity and fate depend on specific sets of transcript isoforms generated by post-transcriptional RNA processing. Here, we used Schmidtea mediterranea, a flatworm with extraordinary regenerative abilities and a large pool of adult stem cells, as an in vivo model to study the role of Uridyl-rich small nuclear RNAs (UsnRNAs), which participate in multiple RNA processing reactions including splicing, in stem cell regulation. We characterized the planarian UsnRNA repertoire, identified stem cell-enriched variants and obtained strong evidence for an increased rate of UsnRNA 3'-processing in stem cells compared to their differentiated counterparts. Consistently, components of the Integrator complex showed stem cell-enriched expression and their depletion by RNAi disrupted UsnRNA processing resulting in global changes of splicing patterns and reduced processing of histone mRNAs. Interestingly, loss of Integrator complex function disrupted both stem cell maintenance and regeneration of tissues. Our data show that the function of the Integrator complex in UsnRNA 3'-processing is conserved in planarians and essential for maintaining their stem cell pool. We propose that cell type-specific modulation of UsnRNA composition and maturation contributes to in vivo cell fate choices, such as stem cell self-renewal in planarians.

Anti-platelet antibody immunoassays in childhood immune thrombocytopenia: a systematic review.

BACKGROUND: In adult immune thrombocytopenia (ITP), an acquired autoimmune bleeding disorder, anti-platelet autoantibody testing may be useful as a rule-in test. Childhood ITP has different disease characteristics, and the diagnostic and prognostic value of anti-platelet antibody testing remains uncertain. OBJECTIVE: To systematically review the diagnostic accuracy of anti-platelet autoantibody testing in childhood ITP. METHODS: PubMed and EMBASE were searched for studies evaluating immunoassays in childhood ITP. Study quality was assessed (QUADAS2), and evidence was synthesized descriptively. RESULTS: In total, 40 studies (1606 patients) were identified. Nine studies reported sufficient data to determine diagnostic accuracy measures. Anti-platelet IgG antibody testing showed a moderate sensitivity (0·36-0·80 platelet-associated IgG [direct test]; 0·19-0·39 circulating IgG [indirect test]). In studies that reported control data, including patients with non-immune thrombocytopenia, specificity was very good (0·80-1·00). Glycoprotein-specific immunoassays showed comparable sensitivity (three studies) and predominantly identified IgG anti-GP IIb/IIIa antibodies, with few IgG anti-GP Ib/IX antibodies. Anti-platelet IgM antibodies were identified in a substantial proportion of children (sensitivity 0·62-0·64 for direct and indirect tests). CONCLUSION: The diagnostic evaluation of IgG and IgM anti-platelet antibodies may be useful as a rule-in test for ITP. In children with insufficient platelets for a direct test, indirect tests may be performed instead. A negative test does not rule out the diagnosis of ITP. Future studies should evaluate the value of anti-platelet antibody tests in thrombocytopenic children with suspected ITP.

Chiroptical Properties of Indolenine Squaraines with a Stereogenic Center at Close Proximity.

A series of four indolenine squaraines bearing a chiral center at the 3-position of the indolenine moiety, with either an n-propyl or a phenyl group alongside a methyl group, were synthesized and obtained in a high purity of ≥98% for the desired stereoisomer. The indolenine precursors with a phenyl group attached at the chiral center were asymmetrically synthesized using a pericyclic-reaction cascade and obtained in a high ee of 98%, whereas the ones with an n-propyl group were prepared by kinetic resolution through asymmetric hydrogenation, resulting in an ee of up to 98%. X-ray crystallography revealed a slightly twisted geometry for the phenyl-substituted cisoid squaraine derivative, whereas the n-propyl-substituted derivative possessed the expected planar geometry. Variation of the substitution also influenced the optical properties, where the introduction of phenyl groups caused a progressive red-shift and reduction in squared transition moments, as well as reduced fluorescence quantum yields, Stokes shifts, and fluorescence lifetimes. All of the investigated compounds exhibited strong ECD signals, with Δε values of up to 24 M-1 cm-1 for the HOMO-LUMO transition. DFT calculations indicated that this was due to both large electric and magnetic transition moments, although the two vectors were mutually almost orthogonal.

On the photophysical properties of IrIII, PtII, and PdII (phenylpyrazole) (phenyldipyrrin) complexes.

The absorption and emission characteristics of (ppz)2(dipy)IrIII, (ppz)(dipy)PtII and (ppz)(dipy)PdII, where ppz stands for phenylpyrazole and dipy for a phenyl meso-substituted dipyrrin ligand, have been investigated by means of combined density functional theory and multireference configuration interaction including scalar relativistic and spin-orbit coupling effects. These results were compared with experimental spectra. The complexes exhibit a high density of low-lying electronically excited states originating from ligand-centered (LC) and metal-to-ligand charge transfer (MLCT) states involving the dipyrrin ligand. In addition, metal-centered (MC) states are found to be low-lying in the Pd complex. In all three cases, the first strong absorption band and the phosphorescence emission band stem from LC excitations on the dipyrrin ligand with small MLCT contributions. The MLCT states show more pronounced relaxation effects than the LC states, with the consequence that the first excited state with predominant singlet multiplicity is of SMLCT/LC type in the heavier Ir and Pt complexes. Substantial spin-orbit coupling between SMLCT/LC and TLC enables fast and efficient intersystem crossing (ISC) and a high triplet quantum yield. Phosphorescence rate constants are rather small in accord with the dominant LC character of the transitions. Out-of-plane distortion promotes nonradiative decay of the excited state population via the MC states thus explaining the lower phosphorescence quantum yield of the Pt complex. The spectral properties of the Pd complex are different in many aspects. Optimization of the S1 state yields a dipyrrin intraligand charge transfer (ILCT) state with highly distorted nuclear arrangement in the butterfly conformers leading to nonradiative deactivation. In contrast, the primarily excited SLC state and the SMLCT/LC state of the twist conformer have nearly equal adiabatic excitation energies. The lack of a driving force toward the SMLCT/LC minimum, the high fluorescence rate constant of the bright SLC state and its moderately efficient ISC to the triplet manifold explain the experimentally observed dual emission of the Pd complex at room temperature.

Workplace-based health research training: a qualitative study of perceived needs in a rural setting.

BACKGROUND: The calls for increased numbers of researchers in rural health are growing. To meet this demand, training is needed. If training is to be effective, the value placed on research, the organisational need for research training and key targets for research skill development within a rural health organisation must be understood. METHODS: This qualitative study was underpinned by a critical realist perspective that allowed exploration of the organisational, cultural and structural contexts of research training and of the ability of individuals to act within these contexts. Individual interviews with purposively selected key informants from the organisation's board, executive and facility management (n = 7) and two focus groups with a convenience sample of frontline health workers with interests in research (total n = 11) were held. Data were analysed using NVivo software and thematic analysis. RESULTS: The themes emerging from this study were the fragmentation of research activity, a need for systems that support research and collaboration for expertise. CONCLUSIONS: This study has identified an overreliance on individual activity leading to a fragmented approach to research. There is a need for supportive structures, coordination and workplace leadership to overcome a longstanding culture that views research as out of the rural scope of practice. Identifying research training targets, partnering for educational expertise and planning for long-term sustainability are necessary steps toward increasing research activity in the longer term.

Decision-making capacity assessment for confused patients in a regional hospital: A before and after study.

OBJECTIVE: Clinicians are challenged to decide when and how to conduct decision-making capacity assessment and guardianship applications for confused hospitalised older patients. This study aimed to understand the characteristics of confused hospitalised older patients who require decision-making capacity assessment and guardianship applications and to determine the impact of a locally introduced capacity testing procedure on the conduct of decision-making capacity assessment and guardianship application in a regional hospital setting. DESIGN: Before and after study. SETTING: Regional New South Wales hospital. PARTICIPANTS: Twenty-four confused hospitalised older patients who had decision-making capacity assessment during November 2014-April 2015 and November 2015-April 2016. MAIN OUTCOME MEASURE: The impact of a standardised capacity testing procedure on the conduct of decision-making capacity assessment. RESULTS: After capacity testing procedure implementation, there were significant improvements in the number of multidisciplinary team meetings, documentation of decision-making capacity assessment process and length of stay. The majority of patients who required guardianship application was aged over 70 years, had a medical history of dementia, >20 days of acute hospital admission and had no evidence of future care-planning. CONCLUSION: Implementation of capacity testing procedure is likely to have contributed to the positive changes in the conduct of decision-making capacity assessment and guardianship application process for confused hospitalised older patients. This study provides some evidence of decision-making capacity assessment process gaps; and indicates clinical and demographic characteristics of confused hospitalised older patients who might require decision-making capacity assessment and guardianship applications. The evidence of lack of appropriate future care-planning for ageing patients and increasing hospital admissions of confused hospitalised older patients presents future challenges in rural health.