Calcareous termite mounds in South Africa are ancient carbon reservoirs.

Ecosystems that offer carbon sequestration by leaching bicarbonate to groundwater are valuable natural capital. One region that may offer this service is the west coast of South Africa. Over 20 % is covered by soil mounds ("heuweltjies") up to 40 m diameter, 2 m high, inhabited by the southern harvester termite Microhodotermes viator and enriched in soil organic and inorganic carbon and soluble minerals. We aimed to generate radiogenic and stable isotope data for soils and groundwater in a region where these data are absent, to 1) verify the atmosphere-soil-groundwater link, and 2) resolve the timing and pattern of calcite dissolution and water infiltration in the landscape. Results show that soil and groundwater sulfate have the same marine aerosol source. Episodic calcite dissolution in mound centers, which increased during periods of global cooling, has been set against background input of marine aerosols since before the Last Glacial according to radiocarbon (14C) ages. Our data push back soil organic carbon 14C ages of inhabited termite mounds to 13-19 ka (kiloannum, thousand years before present), nest carbonate 14C ages to 33 ka, and mound soil carbonate 14C ages to 34 ka, making these the oldest active termite features ever dated. These ages are consistent with soil organic carbon and carbonate 14C ages of regional, non-mound, coastal petrocalcic horizons formed by accumulation of carbonate leached from their overlying aeolian dune fields. Harvesting activities of termites inject younger organic material around nests >1 m deep, leading to continuous renewal of important soil carbon reservoirs at depth. Termite bioturbation increases the system's ability to dissolve carbonate. The central, bioturbated part of the mounds have greater infiltration depths and greater calcite dissolution, whereas surrounding soils experienced more surface runoff. Calcareous termite mounds offer a mechanism to sequester CO2 through dissolution and leaching of soil carbonate-bicarbonate to groundwater.

Long-term Effectiveness of Adjuvant Treatment With Catechol-O-Methyltransferase or Monoamine Oxidase B Inhibitors Compared With Dopamine Agonists Among Patients With Parkinson Disease Uncontrolled by Levodopa Therapy: The PD MED Randomized Clinical Trial.

Importance: Many people with Parkinson disease (PD) develop motor complications that are uncontrolled by levodopa dose adjustment. Among these patients, it is uncertain which drug class is more effective as adjuvant therapy. Objective: To compare the long-term effects on patient-rated quality of life of adding a dopamine agonist vs a dopamine reuptake inhibitor (DRI), either a monoamine oxidase type B (MAO-B) inhibitor or a catechol-O-methyltransferase (COMT) inhibitor, to levodopa therapy for the treatment of patients with motor complications of PD. Design, Setting, and Participants: This pragmatic semifactorial (2 × 1) randomized clinical trial recruited from 64 neurology and geriatric clinics (62 in the United Kingdom, 1 in the Czech Republic, and 1 in Russia) between February 23, 2001, and December 15, 2009. A total of 500 patients with idiopathic PD who developed uncontrolled motor complications and did not have dementia were randomly assigned on a 1:1:1 basis using a computerized minimization program. Data were analyzed between 2017 and 2020. Interventions: Open-label dopamine agonist, MAO-B inhibitor, or COMT inhibitor. Main Outcomes and Measures: Primary outcomes were scores on the 39-item Parkinson's Disease Questionnaire (PDQ-39) mobility domain and cost-effectiveness. Outcomes were assessed before study entry, at 6 and 12 months after randomization, and annually thereafter. Repeated-measures and log rank analyses were used in an intention-to-treat approach. Results: Among 500 participants, the mean (SD) age was 73.0 (8.2) years; 314 participants (62.8%) were men. Over a median of 4.5 years (range, 0-13.3 years) of follow-up, the participants in the dopamine agonist group had a mean PDQ-39 mobility score that was 2.4 points (95% CI, -1.3 to 6.0 points) better than that of the combined MAO-B and COMT groups; however, this difference was not significant (P=.20). With regard to DRIs, participants in the MAO-B group had mean PDQ-39 mobility scores that were 4.2 points (95% CI, 0.4-7.9 points; P=.03) better than those of the COMT group and EuroQol 5-dimension 3-level (EQ-5D-3L) utility scores that were 0.05 points (95% CI, 0.003-0.09 points; P=.04) better than the COMT group. Nonsignificant improvements were found in the PDQ-39 summary index (mean difference, 2.2 points; 95% CI, -0.2 to 4.5 points; P=.07) along with nonsignificant reductions in dementia (rate ratio [RR], 0.70; 95% CI, 0.47-1.03; P = .07) and mortality (RR, 0.76; 95% CI, 0.56-1.03; P=.07). When dopamine agonists were compared with MAO-B inhibitors only, the outcomes were similar. Conclusions and Relevance: In this study, patient-rated quality of life was inferior when COMT inhibitors were used as adjuvant treatment compared with MAO-B inhibitors or dopamine agonists among people with PD who experienced motor complications that were uncontrolled by levodopa therapy. The MAO-B inhibitors produced equivalent disease control, suggesting that these agents may be underused as adjuvant therapy. Trial Registration: isrctn.org Identifier: ISRCTN69812316; EU Clinical Trials Register Identifier: 2005-001813-16.

Saline groundwater in the Buffels River catchment, Namaqualand, South Africa: A new look at an old problem.

Namaqualand, South Africa, is a global biodiversity hotspot but local populations are affected by challenging economic conditions largely because of poor access to water. In this study groundwater types are characterised and sources of salts and salinisation processes are identified using hydrochemistry and δ18O, δ2H and 87Sr/86Sr data. Analysis of δ18O and δ2H data suggests that evaporation does not play a major role in salinisation of the groundwater. However, major ion chemistry and 87Sr/86Sr ratios indicate that salts present in the groundwater are linked to dry deposition of marine aerosols and ion-exchange reactions in soils in the alluvial aquifer systems. The hydrochemical variability of the groundwater in the basement aquifer system suggests that there are strong local controls linked to weathering processes in individual basement rock types. The region is also notable for the high density of heuweltjies, biophysical features associated with increased nutrient levels, associated with termite activity. Electromagnetic scanning as well as measurement of water-soluble soil electrical conductivity values on and off heuweltjies, show that heuweltjies are saline with salinity increasing with depth. The level of groundwater salinity correlates with the level of heuweltjie salinity. Precipitation records from the last 150 years provide support for the hypothesis that accumulated salts, and in particular, heuweltjie salts are flushed into the groundwater system during sporadic large volume precipitation events. Thus, heuweltjies and hence termite activity, could potentially represent a previously unrecognized contributor to groundwater salinisation across Namaqualand and in other parts of the world.

A multicentre, randomised controlled trial to compare the clinical and cost-effectiveness of Lee Silverman Voice Treatment versus standard NHS Speech and Language Therapy versus control in Parkinson's disease: a study protocol for a randomised controlled trial.

BACKGROUND: Parkinson's disease (PD) affects approximately 145,519 people in the UK. Speech impairments are common with a reported prevalence of 68%, which increase physical and mental demands during conversation, reliance on family and/or carers, and the likelihood of social withdrawal reducing quality of life. In the UK, two approaches to Speech and Language Therapy (SLT) intervention are commonly available: National Health Service (NHS) SLT or Lee Silverman Voice Treatment (LSVT LOUD®). NHS SLT is tailored to the individuals' needs per local practice typically consisting of six to eight weekly sessions; LSVT LOUD® comprises 16 sessions of individual treatment with home-based practice over 4 weeks. The evidence-base for their effectiveness is inconclusive. METHODS/DESIGN: PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Five hundred and forty-six people with idiopathic PD, reporting speech or voice problems will be enrolled. We will exclude those with a diagnosis of dementia, laryngeal pathology or those who have received SLT for speech problems in the previous 2 years. Following informed consent and completion of baseline assessments, participants will be randomised in a 1:1:1 ratio to no-intervention control, NHS SLT or LSVT LOUD® via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Participants randomised to the intervention groups will start treatment within 4 (NHS SLT) or 7 (LSVT LOUD®) weeks of randomisation. PRIMARY OUTCOME: Voice Handicap Index (VHI) total score at 3 months. Secondary outcomes include: VHI subscales, Parkinson's Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5 L; ICECAP-O; resource utilisation; adverse events and carer quality of life. Mixed-methods process and health economic evaluations will take place alongside the trial. Assessments will be completed before randomisation and at 3, 6 and 12 months after randomisation. The trial started in December 2015 and will run for 77 months. Recruitment will take place in approximately 42 sites around the UK. DISCUSSION: The trial will test the hypothesis that SLT is effective for the treatment of speech or voice problems in people with PD compared to no SLT. It will further test whether NHS SLT or LSVT LOUD® provide greater benefit and determine the cost-effectiveness of both interventions. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 12421382. Registered on 18 April 2016.

Coding accuracy for Parkinson's disease hospital admissions: implications for healthcare planning in the UK.

OBJECTIVES: Hospital Episode Statistics data are used for healthcare planning and hospital reimbursements. Reliability of these data is dependent on the accuracy of individual hospitals reporting Secondary Uses Service (SUS) which includes hospitalisation. The number and coding accuracy for Parkinson's disease hospital admissions at a tertiary centre in Birmingham was assessed. STUDY DESIGN: Retrospective, routine-data-based study. METHODS: A retrospective electronic database search for all Parkinson's disease patients admitted to the tertiary hospital over a 4-year period (2009-2013) was performed on the SUS database using International Classification of Disease codes, and on the local inpatient electronic prescription database, Prescription and Information Communications System, using medication prescriptions. Capture-recapture methods were used to estimate the number of patients and admissions missed by both databases. RESULTS: From the two databases, between July 2009 and June 2013, 1068 patients with Parkinson's disease accounted for 1999 admissions. During these admissions, the Parkinson's disease was coded as a primary or secondary diagnosis. Ninety-one percent of these admissions were recorded on the SUS database. Capture-recapture methods estimated that the number of Parkinson's disease patients admitted during this period was 1127 patients (95% confidence interval: 1107-1146). A supplementary search of both SUS and Prescription and Information Communications System was undertaken using the hospital numbers of these 1068 patients. This identified another 479 admissions. SUS database under-estimated Parkinson's disease admissions by 27% during the study period. CONCLUSION: The accuracy of disease coding is critical for healthcare policy planning and must be improved. If the under-reporting of Parkinson's disease admissions on the SUS database is repeated nationally, expenditure on Parkinson's disease admissions in England is under-estimated by approximately £61 million per year.

A systematic review of interventions to reduce hospitalisation in Parkinson's disease.

UNLABELLED: The neurodegenerative process in Parkinson's disease (PD) results in a relentless progression of motor and non-motor symptoms. Affected individuals are frequently hospitalised for complications of the disease including falls, fractures, infections, and neuropsychiatric symptoms. When admitted to hospital, inpatient care is often suboptimal as it focusses on the primary cause of admission, and is associated with poor patient outcomes and significant healthcare costs. AIM: To review existing literature for evidence-based interventions aimed at reducing hospital admissions in PD. METHODS: Electronic literature search in EMBASE, MEDLINE and CINAHL databases for studies evaluating interventions to reduce hospital admissions in PD. We included publications with full abstracts, published in the English language and addressing interventions to reduce hospital admissions in PD. RESULTS: To date there are no randomised controlled trials addressing the topic. We identified nine relevant retrospective studies. Results from these studies suggest an association between frequent neurologist consultations, open access clinics, and medication compliance with a reduction in PD hospital admissions and emergency room visits. CONCLUSION: This systematic review highlights the lack of robust evidence for measures aimed at reducing hospital admissions in people with PD. Future prospective studies are required to evaluate the effectiveness of proposed interventions.

The inpatient neurology consultation service: value and cost.

Neurological conditions comprise a significant proportion of patient admissions to hospital but, in the majority of cases, are admitted under the care of non-neurological physicians. As a consequence, neurological ward consultations are commonly requested by the admitting medical teams to review diagnoses and management plans. The outcomes of neurological ward consultations were examined and the time required for the referral process recorded by performing a detailed prospective three-month audit of inpatient referrals to the neurology service. The consultations of 120 patients were recorded, categorised and analysed. These consultations were beneficial in the vast majority of cases, with a clear impact on patient diagnoses or management plans. The consultation process was time consuming, however, both in respect of the initial review, but also with follow-up visits. This audit highlights the importance of neurological input in the diagnosis and management of hospital inpatients. The time taken for this process should be resourced appropriately.

Has drug therapy changed the natural history of Parkinson's disease?

This narrative review examines the effects of drug therapy on the natural history of Parkinson's disease. In terms of modifying the underlying disease process, it is possible that immediate therapy, rather than deferred treatment, can have a positive effect on the underlying disease process. However, it is unlikely that drug therapy has changed mortality from the condition and there is no evidence that it can delay the onset of non-motor features such as dementia and falls. The beneficial effects of drug therapy on the motor symptoms of Parkinson's disease are unquestionable, but these are at the expense of short-term dopaminergic side effects, long-term motor complications, and impulse control disorders. Major questions remain regarding which initial therapeutic approach should be taken which may possibly be answered by the ongoing PD MED trial. The beneficial effects of drug therapy on the motor features of Parkinson's disease have had a fundamental impact on the suffering of patients. The mainstay of these therapies continues to be levodopa, although it is now used at lower doses than in the past and in combination with other drug classes.

The use of complementary and alternative medicine by patients attending a UK headache clinic.

OBJECTIVES: This study was undertaken in order to determine the extent of the use of CAM in a UK headache clinic. DESIGN: Ninety-two patients attending a headache clinic were given a questionnaire containing questions regarding their headaches and their use of CAM for headaches. SETTING: Outpatient headache clinic, Birmingham, UK. Main outcome measures. The use of complementary and alternative therapies and predictive factors. RESULTS: 32% of respondents had used a median of 3 different CAM therapies for their headache. The commonest source of recommendation of CAM use was a friend or relative (72%) and the commonest reason given for using CAM was as a last resort after trying all conventional therapies offered (48%). CAM therapies were perceived as beneficial by 60% of CAM users and no users perceived the CAM therapy to worsen their headache. 42% of CAM users had not disclosed it to their doctor or nurse, 80% of these giving the reason that the doctor or nurse never asked, rather than fear of discouragement or lack of understanding. Individuals who were in employment were more likely to have used CAM than those who were not. Binary logistic regression revealed Headache Impact Test (HIT-6) score to be a significant predictor of CAM use (Odds Ratio=1.38 [95% CI 1.05-1.81]). CONCLUSIONS: As a matter of desperation, headache clinic patients try CAM therapies. Health care professionals involved in the management of headache should be aware of this. There is a need for evaluation of the benefits and safety of CAM therapies for headache.

Imaging results in a consecutive series of 530 new patients in the Birmingham Headache Service.

Guidelines recommend imaging only headache patients with sinister features in the history or on examination. We prospectively collected data on imaging newly presenting patients to a UK headache service. CT and MRI results were classified as normal or showing an insignificant or significant abnormality. Over 5 years, 3,655 new patients (69% female; mean age 42.0 years) with headache disorders were seen. Five hundred thirty (14.5%) underwent imaging with large differences in the proportion referred by each consultant. There were more insignificant abnormalities on MRI (46%) than CT (28%). There were 11 significantly abnormal results (2.1% of those imaged). Significant abnormalities were found in patients diagnosed with migraine in 1.2% and in 0.9% of those with tension-type headache. Significant abnormalities in those suspected to have an intracranial abnormality occurred in 5.5%. This supports the practice of selecting patients with suspicious findings for imaging, rather than imaging all patients.

Idiopathic intracranial hypertension associated with iron deficiency anaemia: a lesson for management.

AIM: To document the causal association of iron deficiency anaemia (IDA) and intracranial hypertension (IH). METHODS: A consecutive case note review of patients with a clinical diagnosis of idiopathic intracranial hypertension (IIH) and anaemia presenting to a tertiary referral unit over a 2.5-year period. Demographics, aetiology and clinical details were recorded and analysed. RESULTS: Eight cases were identified from 77 new cases presenting with IIH. All 8 had documented microcytic anaemia with clinical evidence of raised intracranial pressure. There was no evidence of venous sinus thrombosis on MRI and MR venography in 7 subjects and on repeated CT venography in 1. On correction of anaemia alone, 7 cases resolved. One patient with severe progressive visual loss underwent ventriculoperitoneal shunt in addition to treatment of anaemia, with good outcome. The incidence of this association is 10.3%. CONCLUSION: These cases present an association between IDA and IH, in the absence of cerebral sinus thrombosis. As a clinically significant proportion of cases presenting with signs of IIH have IDA, we recommend all patients presenting with IIH have full blood counts and if they are found to be anaemic, they should be treated appropriately.

Elevated cerebrospinal fluid (CSF) leptin in idiopathic intracranial hypertension (IIH): evidence for hypothalamic leptin resistance?

OBJECTIVE: The aetiology of idiopathic intracranial hypertension (IIH) is not known, but its association with obesity is well-recognized. Recent studies have linked obesity with abnormalities in circulating inflammatory and adiposity related cytokines. The aim of this study was to characterize adipokine and inflammatory cytokine profiles in IIH. DESIGN: Paired serum and cerebrospinal fluid (CSF) specimens were collected from 26 patients with IIH and compared to 62 control subjects. Samples were analysed for leptin, resistin, adiponectin, insulin, IL-1beta, IL-6, IL-8 (CXCL8), TNFalpha, MCP-1 (CCL2), hepatocyte growth factor, nerve growth factor and PAI-1 using multiplex bead immunoassays. RESULTS: CSF leptin was significantly higher in patients with IIH (P = 0.001) compared to controls after correction for age, gender and body mass index (BMI). In the control population, BMI correlated with serum leptin (r = 0.34; P = 0.007) and CSF leptin (r = 0.51; P < 0.0001), but this was not the case for the IIH population. Profiles of other inflammatory cytokines and adipokines did not differ between IIH patients and controls once anthropometric factors had been accounted for. CONCLUSIONS: IIH was characterized by significantly elevated CSF leptin levels which did not correlate with BMI. We suggest that CSF leptin may be important in the pathophysiology of IIH and that obesity in IIH may occur as a result of hypothalamic leptin resistance.

Pilot randomised controlled trial of occupational therapy to optimise independence in Parkinson's disease: the PD OT trial.

OBJECTIVE: To perform a pilot trial of occupational therapy (OT) to optimise functional independence in Parkinson disease (PD) to assess accrual/withdrawal rates, acceptability, outcome measures, and inform sample-size calculation. METHOD: Non-demented patients with idiopathic PD and difficulties with activities of daily living (ADL) were recruited provided they had not received OT in the last 2 years and/or physiotherapy in the last year. Patients were randomised to immediate OT or OT after completion of the trial. Patients randomised to OT were assessed at home by an experienced therapist and then received six home treatment sessions over 2 months. Interventions were targeted at functional independence and mobility goals. Outcome measures were: Nottingham Extended Activity of Daily Living Scale, Rivermead Mobility Index, Unified Parkinson's Disease Rating Scale ADL scale, Parkinson's Disease Questionnaire 39, EuroQol-EQ-5D, Hospital Anxiety and Depression Scale, and health economics analysis. RESULTS: 39 patients (25 male; mean age 73 years) were recruited from four centres over 16 months. The mean difference in NEADL at 8 months was 3.5 (95% CI -3.2 to 10.2). The mean difference in PDQ-39 Summary Score was 3.8 (95% CI -4.94 to 12.6). There were strong correlations between the PDQ-39 and other outcomes. The intervention was acceptable to patients, with a low withdrawal rate and good questionnaire completion. CONCLUSION: Randomisation to a trial of OT in PD is feasible. NEADL and PDQ-39 are relevant outcomes and provided data to inform sample size for an adequately powered randomised trial for which there is pressing need.

Identification of a region in the TASK3 two pore domain potassium channel that is critical for its blockade by methanandamide.

BACKGROUND AND PURPOSE: The TASK subfamily of two pore domain potassium channels (K2P) encodes for leak K currents, contributing to the resting membrane potential of many neurons and regulating their excitability. TASK1 and TASK3 channels are regulated by a number of pharmacological and physiological mediators including cannabinoids such as methanandamide. In this study, we investigate how methanandamide blocks these channels. EXPERIMENTAL APPROACH: Currents through wild type and mutated TASK1 and TASK3 channels expressed in modified HEK-293 cells were measured using whole-cell electrophysiological recordings in the presence and absence of methanandamide. KEY RESULTS: Methanandamide (3 microM) produced substantial block of hTASK1, hTASK3 and mTASK3 channels but was most potent at blocking hTASK3 channels. Block of these channels was irreversible unless cells were washed with buffer containing bovine serum albumin. Mutation of the distal six amino acids of TASK1 did not alter methanandamide inhibition, whilst C terminal truncation of TASK3 channels caused a small but significant reduction of inhibition. However, deletion of six amino acids (VLRFLT) at the interface between the final transmembrane domain and cytoplasmic C terminus of TASK3 channels gave functional currents that were no longer inhibited by methanandamide or by activation of GPCRs. CONCLUSIONS AND IMPLICATIONS: Methanandamide potently blocked TASK3 and TASK1 channels and both methanandamide and G protein-mediated inhibition converged on the same intracellular gating pathway. Physiologically, methanandamide block of TASK1 and TASK3 channels may underpin a number of CNS effects of cannabinoids that are not mediated through activation of CB1 or CB2 receptors.