Pore fluid constraints on deep ocean temperature and salinity during the Last Glacial Maximum

Pore water records of δ^(18)O and [Cl] from ODP Site 1063A on the Bermuda Rise constrain the change in seawater δ^(18)O and salinity from the Last Glacial Maximum (LGM) to the Holocene to be 0.75±0.05‰ and 2.5±0.1% respectively. Coupled with a measured benthic foraminiferal δ^(18)O change, this result means that bottom waters were 4.6±0.8°C cooler than the Holocene at the LGM and therefore at or near the seawater freezing point. Coupled δ^(18)O and chlorinity results give an extrapolated mean ocean LGM to Holocene change in δ^(18)O of 0.95±0.09‰. These data also constrain the past southern source deep‐water salinity to be 35.76±0.04 psu, which is within error of the mean deep ocean value for this time

Electro-impulse de-icing testing analysis and design

Electro-Impulse De-Icing (EIDI) is a method of ice removal by sharp blows delivered by a transient electromagnetic field. Detailed results are given for studies of the electrodynamic phenomena. Structural dynamic tests and computations are described. Also reported are ten sets of tests at NASA's Icing Research Tunnel and flight tests by NASA and Cessna Aircraft Company. Fabrication of system components are described and illustrated. Fatigue and electromagnetic interference tests are reported. Here, the necessary information for the design of an EIDI system for aircraft is provided

Why do patients with Parkinson's disease fall? A cross-sectional analysis of possible causes of falls.

Background: Falls in Parkinson’s disease (PD) are associated with significant injury, disability, hospitalization, and reduced quality of life. Aims: To identify modifiable medical causes of falls in a cohort of PD patients. Methods: Eighty seven PD patients were interviewed and examined using validated scales assessing motor and nonmotor aspects of PD, comorbidities and medication use. The frequency of falls in the last month was the primary outcome measure. Falls were hypothesized to be associated with increasing age, advanced motor severity, particularly axial features (e.g., freezing and postural instability), and dyskinesia. Nonmotor features hypothesized to be associated with falls included; cognitive impairment, psychosis, sleep disorders, cardiovascular dysfunction, and ophthalmological and medical comorbidities. Results: Fallers had longer disease duration, higher Levodopa-equivalent doses, greater ‘On’ time with dyskinesia (all P<0.005), and higher scores on some Movement Disorder Society-Unified Parkinson’s Disease Rating Scale items, particularly axial scores. However, patients with falls did not differ from non-fallers in age or overall motor UPDRS scores. Severity of psychosis, executive cognitive impairment, autonomic (particularly cardiovascular) dysfunction and sleep disturbances (particularly REM sleep behavioral disorder) were significantly associated with falls (all P<0.005). Fallers more frequently reported use of antidepressants (both tricyclics and SSRIs) and neuroleptics (P<0.001), but not hypnotics. There was no difference in medical comorbidities, ophthalmological assessments, fatigue, and apathy scores between the groups. In logistic regression analysis, cardiovascular dysfunction, antidepressant use, and REM sleep behavioral disorder were significantly associated with falls. Conclusions: The causes of falls in PD are multifactorial and extend beyond motor impairment and dyskinesia; addressing these in patients already treated with dopaminergic medications has the potential to improve this important complication of PD

Pancreatic lipases: evolutionary intermediates in a positional change of catalytic carboxylates?

Comparison of the fold of lipases from Geotrichum candidum and from human pancreas identified a high degree of similarity which was not expected on the basis of their amino acid sequences. Although both enzymes utilize a serine protease-like catalytic triad, they differ in the topological position of the acid. We speculate that these proteins are evolutionarily related and that the pancreatic lipase is an evolutionary intermediate in the pathway of migration of the catalytic acid to a new position within the fold

Orthostatic Hypotension and Antiparkinsonian Drugs: A Systematic Review and Meta-analysis

BACKGROUND: Orthostatic hypotension (OH) is multifactorial in Parkinson's disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls, weakness and fatigue. METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of antiparkinsonian drugs associated with OH as an adverse effect, compared to placebo. We searched EMBASE, MEDLINE and Web of Science databases until November 2020. Analysis used fixed-effects models and the GRADE tool to rate quality of evidence. Meta-analysis was performed if 3 or more studies of a drug group were available. RESULTS: Twenty-one RCTs including 3783 patients were included comparing 6 PD drug groups to placebo (MAO-B inhibitors, dopamine agonists, levodopa, COMT inhibitors, levodopa and adenosine receptor antagonists). OH was recorded as an adverse event or measurement of vital signs, without further specification on how this was defined or operationalised. Meta-analysis was performed for MAO-B inhibitors and dopamine agonists, as there were 3 or more studies for these drug groups. In this analysis, compared with placebo, neither MAO-B inhibitors or dopamine agonists were associated with increased risk of OH, (OR 2.28 [95% CI:0.81-6.46]), (OR 1.39 [95% CI:0.97-1.98]). CONCLUSIONS: Most studies did not specifically report OH, or reporting of OH was limited, including how and when it was measured. Furthermore, studies specifically reporting OH included participants that were younger than typical PD populations without multimorbidity. Future trials should address this, for example,, by including individuals over the age of 75, to improve estimations of how antiparkinsonian medications affect risk of OH

Oncology in Transition

Contemporary challenges and changes in the field of oncology reflect and often magnify medicine more broadly. Morbidity and mortality are often substantial, treatment is expensive, and management is complex necessitating interdisciplinary coordination across every field of medicine. The recent emergence of immunotherapy and adoptive cellular therapy has generated tremendous excitement because these approaches can sometimes achieve cure or durable responses, even in the setting of advanced cancer

The Evolving Uses of "Real-World" Data

The terms real-world data (RWD) and real-world evidence (RWE) have entered the medical lexicon to refer to data sources and analyses characterizing routine health care delivery. RWD and RWE are most often defined by what they are not: information from experiments such as randomized clinical trials

Experiences of advance care planning in Parkinson’s disease and atypical Parkinsonian disorders: a mixed methods systematic review

Background and purpose: Advance care planning allows people to plan for their future care needs and can include medical, psychological and social aspects. However, little is known on the use, experience of and attitudes towards advance care planning in patients with parkinsonian disorders, their family carers and healthcare professionals. Methods: A systematic search of online databases was conducted in April 2019 using a narrative synthesis approach with thematic analysis and tabulation to synthesize the findings. Results: In all, 507 articles were identified and 27 were included. There were five overarching themes: (i) what is involved in advance care planning discussions, (ii) when and how advance care planning discussions are initiated, (iii) barriers to advance care planning, (iv) the role of healthcare professionals and (v) the role of the family carer. This evidence was used to highlight eight effective components to support optimal advance care planning in parkinsonian disorders: advance care planning discussions should be individualized in content, timing and approach; patients should be invited to discuss advance care planning early and regularly; palliative care services should be introduced early; a skilled professional should deliver advance care planning; support to family carers should be offered in the advance care planning process; healthcare professionals should be educated on parkinsonian disorders and palliative care; advance care planning should be clearly documented and shared with relevant services; and healthcare professionals should be enabled to conduct effective advance care planning. Conclusions: These components can inform best practice in advance care planning in patients with parkinsonian disorders

The neuropsychiatry of Parkinson's disease: advances and challenges

In people with Parkinson's disease, neuropsychiatric signs and symptoms are common throughout the disease course. These symptoms can be disabling and as clinically relevant as motor symptoms, and their presentation can be similar to, or distinct from, their counterparts in the general population. Correlates and risk factors for developing neuropsychiatric signs and symptoms include demographic, clinical, and psychosocial characteristics. The underlying neurobiology of these presentations is complex and not well understood, with the strongest evidence for neuropathological changes associated with Parkinson's disease, mechanisms linked to dopaminergic therapy, and effects not specific to Parkinson's disease. Assessment instruments and formal diagnostic criteria exist, but there is little routine screening of these signs and symptoms in clinical practice. Mounting evidence supports a range of pharmacological and non-pharmacological interventions, but relatively few efficacious treatment options exist. Optimising the management of neuropsychiatric presentations in people with Parkinson's disease will require additional research, raised awareness, specialised training, and development of innovative models of care