Outcome and feasibility of radiotherapy bridging in large B-cell lymphoma patients receiving CD19 CAR T in the UK.

Radiotherapy (RT) has potential synergistic effects with chimeric antigen receptor (CAR) T but is not widely used as bridging therapy due to logistical challenges and lack of standardised protocols. We analysed RT bridging in a multicentre national cohort of large B-cell lymphoma patients approved for 3L axicabtagene ciloleucel or tisagenlecleucel across 12 UK centres. Of 763 approved patients, 722 were leukapheresed, 717 had data available on bridging therapy. 169/717 (24%) received RT bridging, 129 as single modality and 40 as combined modality treatment (CMT). Of 169 patients, 65.7% had advanced stage, 36.9% bulky disease, 86.5% elevated LDH, 41.7% international prognostic index (IPI) ≥3 and 15.2% double/triple hit at the time of approval. Use of RT bridging varied from 11% to 32% between centres and increased over time. Vein-to-vein time and infusion rate did not differ between bridging modalities. RT-bridged patients had favourable outcomes with 1-year progression-free survival (PFS) of 56% for single modality and 47% for CMT (1-year PFS 43% for systemic bridging). This is the largest cohort of LBCL patients receiving RT bridging prior to CAR T reported to date. Our results show that RT bridging can be safely and effectively used even in advanced stage and high-risk disease, with low dropout rates and excellent outcomes.

C-STIM: Protocol for a randomized, single-blind, crossover study of cerebellar repetitive transcranial magnetic stimulation (rTMS) for postural instability in people with progressive supranuclear palsy (PSP).

Background: Methods for modulating the cerebellum with transcranial magnetic stimulation (TMS) are well established, and preliminary data from our group and others has shown evidence of transient improvements in balance after cerebellar repetitive transcranial magnetic stimulation (rTMS) in progressive suprancuclear palsy (PSP). This study examines extensive posturography measures before and after 10 sessions of cerebellar rTMS and sham TMS in PSP. Methods: Thirty subjects with PSP and postural instability will undergo cerebellar active and sham rTMS in a single-blind, crossover design with a randomized order of a 10-day intervention. Primary outcomes will be changes in sway area and medio-lateral range of sway with eyes open while standing on a stationary force-plate, and safety, tolerability, and blindedness. Secondary outcomes will include posturography and gait analysis with body-worn, triaxial inertial sensors, clinical balance scales and questionnaires, and a bedside test of vestibular function. Exploratory outcomes are changes in functional near infrared spectroscopy (fNIRS) signal over the prefrontal, supplementary motor, and primary motor cortices while standing and walking, and speech samples for future analysis. Discussion: The C-STIM crossover intervention study adds a longer duration of stimulation and extensive posturography measures to more finely measure the improvements in balance and exploratory functional near-infrared spectroscopy (fNIRS) over the prefronal, supplementary motor, and primary motor cortices during balance assessments before and after 10 sessions of cerebellar rTMS and 10 sessions of sham cerebellar TMS. This project will improve our understanding of the importance of the cerebellum for control of postural stability in PSP.

Ecchordosis Physaliphora: Does It Even Exist?

The term ecchordosis physaliphora (EP) has been used historically to describe a benign notochordal remnant with no growth potential, most commonly occuring in the central clivus. Unfortunately, the radiologic appearance of EP overlaps considerably with the appearance of low-grade chordomas, which do have the potential for growth. In this article, we review new pathologic terminology that better describes this family of diseases, and we propose new radiologic terms that better address the uncertainty of the radiologic diagnosis. The surgical importance of accurate terminology and the implications for patient care are discussed.

Detailed Sub-study Analysis of the SECRAB Trial: Quality of Life, Cosmesis and Chemotherapy Dose Intensity.

AIMS: SECRAB was a prospective, open-label, multicentre, randomised phase III trial comparing synchronous to sequential chemoradiotherapy (CRT). Conducted in 48 UK centres, it recruited 2297 patients (1150 synchronous and 1146 sequential) between 2 July 1998 and 25 March 2004. SECRAB reported a positive therapeutic benefit of using adjuvant synchronous CRT in the management of breast cancer; 10-year local recurrence rates reduced from 7.1% to 4.6% (P = 0.012). The greatest benefit was seen in patients treated with anthracycline-cyclophosphamide, methotrexate, 5-fluorouracil (CMF) rather than CMF. The aim of its sub-studies reported here was to assess whether quality of life (QoL), cosmesis or chemotherapy dose intensity differed between the two CRT regimens. MATERIALS AND METHODS: The QoL sub-study used EORTC QLQ-C30, EORTC QLQ-BR23 and the Women's Health Questionnaire. Cosmesis was assessed: (i) by the treating clinician, (ii) by a validated independent consensus scoring method and (iii) from the patients' perspective by analysing four cosmesis-related QoL questions within the QLQ-BR23. Chemotherapy doses were captured from pharmacy records. The sub-studies were not formally powered; rather, the aim was that at least 300 patients (150 in each arm) were recruited and differences in QoL, cosmesis and dose intensity of chemotherapy assessed. The analysis, therefore, is exploratory in nature. RESULTS: No differences were observed in the change from baseline in QoL between the two arms assessed up to 2 years post-surgery (Global Health Status: -0.05; 95% confidence interval -2.16, 2.06; P = 0.963). No differences in cosmesis were observed (via independent and patient assessment) up to 5 years post-surgery. The percentage of patients receiving the optimal course-delivered dose intensity (≥85%) was not significantly different between the arms (synchronous 88% versus sequential 90%; P = 0.503). CONCLUSIONS: Synchronous CRT is tolerable, deliverable and significantly more effective than sequential, with no serious disadvantages identified when assessing 2-year QoL or 5-year cosmetic differences.

Did the UK's public health shielding policy protect the clinically extremely vulnerable during the COVID-19 pandemic in Wales? Results of EVITE Immunity, a linked data retrospective study.

INTRODUCTION: The UK shielding policy intended to protect people at the highest risk of harm from COVID-19 infection. We aimed to describe intervention effects in Wales at 1 year. METHODS: Retrospective comparison of linked demographic and clinical data for cohorts comprising people identified for shielding from 23 March to 21 May 2020; and the rest of the population. Health records were extracted with event dates between 23 March 2020 and 22 March 2021 for the comparator cohort and from the date of inclusion until 1 year later for the shielded cohort. RESULTS: The shielded cohort included 117,415 people, with 3,086,385 in the comparator cohort. The largest clinical categories in the shielded cohort were severe respiratory condition (35.5%), immunosuppressive therapy (25.9%) and cancer (18.6%). People in the shielded cohort were more likely to be female, aged ≥50 years, living in relatively deprived areas, care home residents and frail. The proportion of people tested for COVID-19 was higher in the shielded cohort (odds ratio [OR] 1.616; 95% confidence interval [CI] 1.597-1.637), with lower positivity rate incident rate ratios 0.716 (95% CI 0.697-0.736). The known infection rate was higher in the shielded cohort (5.9% vs 5.7%). People in the shielded cohort were more likely to die (OR 3.683; 95% CI: 3.583-3.786), have a critical care admission (OR 3.339; 95% CI: 3.111-3.583), hospital emergency admission (OR 2.883; 95% CI: 2.837-2.930), emergency department attendance (OR 1.893; 95% CI: 1.867-1.919) and common mental disorder (OR 1.762; 95% CI: 1.735-1.789). CONCLUSION: Deaths and healthcare utilisation were higher amongst shielded people than the general population, as would be expected in the sicker population. Differences in testing rates, deprivation and pre-existing health are potential confounders; however, lack of clear impact on infection rates raises questions about the success of shielding and indicates that further research is required to fully evaluate this national policy intervention.

A systematic review and meta-analysis of global and social functioning among people at risk of bipolar disorder.

BACKGROUND: Functional status could predict development of bipolar disorder (BD) or have clinical significance. The relationship between BD risk and functioning is poorly understood. We undertook a systematic review examining the global and social functioning of those at risk for BD. METHODS: We examined observational studies comparing a risk sample with healthy controls or full-threshold BD participants, using measures of global or social functioning. Risk status included family history of BD, meeting risk criteria, or having prodromal symptomatology, or premorbid functioning of persons with BD. Medline, PsycINFO, and Embase were searched. The Newcastle-Ottawa Scale for Cross-Sectional Studies was used to assess quality. Meta-analyses were performed where possible. RESULTS: 7215 studies were screened and 40 studies were included (8474 participants). Risk samples had poorer functioning than controls, and superior functioning to participants with BD. Meta-analysis indicated poorer global functioning among persons with familial risk compared to healthy controls (mean global functional difference: 5.92; 95 % confidence interval: 7.90, 3.95; mean premorbid functioning difference: 2.31; 95 % confidence interval: 0.70, 3.92). Studies with higher proportions of female participants had slightly poorer global functioning. High heterogeneity was attributable functional measures and potentially functionally differential subgroups within the risk samples. LIMITATIONS: Broader measures of functioning, such as neurocognition and behavioural measures, were excluded. Measures of global functioning are limited by conflating functioning and symptoms. CONCLUSIONS: Functioning in the BD risk populations is intermediate to that of healthy controls and persons with BD, indicating their value in definitions of BD risk, in itself a likely heterogeneous state.

Exploratory Study of the Brain Response in Facial Synkinesis after Bell Palsy with Systematic Review and Meta-analysis of the Literature.

BACKGROUND: Facial synkinesis, characterized by unintentional facial movements paired with intentional movements, is a debilitating sequela of Bell palsy. PURPOSE: Our aim was to determine whether persistent peripheral nerve changes arising from Bell palsy result in persistent altered brain function in motor pathways in synkinesis. DATA SOURCES: A literature search using terms related to facial paralysis, Bell palsy, synkinesis, and fMRI through May 2021 was conducted in MEDLINE and EMBASE. Additionally, an fMRI study examined lip and eyeblink movements in 2 groups: individuals who fully recovered following Bell palsy and individuals who developed synkinesis. STUDY SELECTION: Task-based data of the whole brain that required lip movements in healthy controls were extracted from 7 publications. Three studies contributed similar whole-brain analyses in acute Bell palsy. DATA ANALYSIS: The meta-analysis of fMRI in healthy control and Bell palsy groups determined common clusters of activation within each group using activation likelihood estimates. A separate fMRI study used multivariate general linear modeling to identify changes associated with synkinesis in smiling and blinking tasks. DATA SYNTHESIS: A region of the precentral gyrus contralateral to the paretic side of the face was hypoactive in synkinesis during lip movements compared with controls. This region was centered in a cluster of activation identified in the meta-analysis of the healthy controls but absent from individuals with Bell palsy. LIMITATIONS: The meta-analysis relied on a small set of studies. The small sample of subjects with synkinesis limited the power of the fMRI analysis. CONCLUSIONS: Premotor pathways show persistent functional changes in synkinesis first identifiable in acute Bell palsy.

Realist analysis of whether emergency departments with primary care services generate 'provider-induced demand'.

BACKGROUND: It is not known whether emergency departments (EDs) with primary care services influence demand for non-urgent care ('provider-induced demand'). We proposed that distinct primary care services in EDs encourages primary care demand, whereas primary care integrated within EDs may be less likely to cause additional demand. We aimed to explore this and explain contexts (C), mechanisms (M) and outcomes (O) influencing demand. METHODS: We used realist evaluation methodology and observed ED service delivery. Twenty-four patients and 106 staff members (including Clinical Directors and General Practitioners) were interviewed at 13 EDs in England and Wales (240 hours of observations across 30 days). Field notes from observations and interviews were analysed by creating 'CMO' configurations to develop and refine theories relating to drivers of demand. RESULTS: EDs with distinct primary care services were perceived to attract demand for primary care because services were visible, known or enabled direct access to health care services. Other influencing factors included patients' experiences of accessing primary care, community care capacity, service design and population characteristics. CONCLUSIONS: Patient, local-system and wider-system factors can contribute to additional demand at EDs that include primary care services. Our findings can inform service providers and policymakers in developing strategies to limit the effect of potential influences on additional demand when demand exceeds capacity.

Use of local anesthesia for inguinal hernia repair has decreased over time in the VA system.

PURPOSE: In 2003, randomized trials demonstrated potentially improved outcomes when local instead of general anesthesia is used for inguinal hernia repair. Our study aimed to evaluate how the use of local anesthesia for this procedure changed over time following the publication of the trials' level 1 evidence. METHODS: We used the 1998-2018 Veterans Affairs Surgical Quality Improvement Program database to identify adults who underwent open, unilateral inguinal hernia repair under local or general anesthesia. Our primary outcome was the percentage of cases performed under local anesthesia. We used a time-series design to examine the trend and rate of change of the use of local anesthesia. RESULTS: We included 97,437 veterans, of which 22,333 (22.9%) had hernia surgery under local anesthesia. The median age of veterans receiving local anesthesia remained stable at 64-67 years over time. The use of local anesthesia decreased steadily, from 38.2% at the beginning year to 15.1% in the final year (P < 0.0001). The publication of results from randomized trials (in 2003) did not appear to increase the overall use or change the rate of decline in the use of local anesthesia. Overall, we found that the use of local anesthesia decreased by about 1.5% per year. CONCLUSION: The utilization of local anesthesia for inguinal hernia repair in the VA has steadily declined over the last 20 + years, despite data showing equivalence or superiority to general anesthesia. Future studies should explore barriers to the use of local anesthesia for hernia repair.

Effectiveness of portable air filtration on reducing indoor aerosol transmission: preclinical observational trials.

BACKGROUND: While the range of possible transmission pathways of severe acute respiratory syndrome coronavirus-2 in various settings has been investigated thoroughly, most authorities have recently acknowledged the role of aerosol spread in its transmission, especially in indoor environments where ventilation is poor. Engineering controls are needed to mitigate aerosol transmission in high-risk settings including hospital wards, classrooms and offices. AIM: To assess the effectiveness of aerosol filtration by portable air cleaning devices with high-efficiency particulate air filters used in addition to a standard building heating ventilation and air conditioning (HVAC) system. METHODS: Test rooms, including a single-bed hospital room, were filled with test aerosol to simulate aerosol movement. Aerosol counts were measured over time with various portable air cleaning devices and room ventilation systems to quantify the overall aerosol clearance rate. FINDINGS: Portable air cleaning devices were very effective for removal of aerosols. The aerosols were cleared five times faster in a small control room with portable air cleaning devices than in the room with HVAC alone. The single-bed hospital room had an excellent ventilation rate (∼14 air changes per hour) and cleared the aerosols in 20 min. However, with the addition of two air cleaning devices, the clearance time was three times faster. CONCLUSIONS: Inexpensive portable air cleaning devices should be considered for small and enclosed spaces in healthcare settings, such as inpatient rooms and personal protective equipment donning/doffing stations. Portable air cleaning devices are particularly important where there is limited ability to reduce aerosol transmission with building HVAC ventilation.

How to make online mood-monitoring in bipolar patients a success? A qualitative exploration of requirements.

BACKGROUND: The Life-Chart Method (LCM) is an effective self-management treatment option in bipolar disorder (BD). There is insufficient knowledge about the consumers' needs and desires for an e-monitoring solution. The first step towards a new mood monitoring application is an extended inventory among consumers and professionals. METHODS: The aim of the current study was: to identify opinions about online mood monitoring of patients with BD and professionals and to identify preferences on design, technical features and options facilitating optimal use and implementation of online mood monitoring. This study used a qualitative design with focus-groups. Participants were recruited among patients and care providers. Three focus-groups were held with eight consumers and five professionals. RESULTS: The focus-group meetings reveal a shared consciousness of the importance of using the Life-Chart Method for online mood monitoring. There is a need for personalization, adjustability, a strict privacy concept, an adjustable graphic report, and a link to early intervention strategies in the design. Due to the fact that this is a qualitative study with a relative small number of participants, so it remains unclear whether the results are fully generalizable. We can't rule out a selection bias. CONCLUSIONS: This study demonstrates the importance of involving stakeholders in identifying a smartphone-based mood charting applications' requirements. Personalization, adjustability, privacy, an adjustable graphic report, and a direct link to early intervention strategies are necessary requirements for a successful design. The results of this value specification are included in the follow-up of this project.

Primer consenso cubano sobre el uso de terapia convencional y biológica en pacientes con artritis reumatoide / First Cuban consensus on the use of conventional and biological therapy in patients with rheumatoid arthritis

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Introduction: The development of recommendations for the treatment of rheumatoid arthritis (RA) in the Cuban context may be one of the ways to achieve better control of this disease. Objective: To reach a consensus and update relevant aspects of conventional and biological RA modifier therapy in Cuba. Methods: 18 specialists from 8 Cuban provinces, experts in RA care, were summoned, according to the years of dedication to the specialty, the conferences on this topic and their publications. The first meeting took place in March 2016 in the provincial hospital of Villa Clara, Cuba, with the participation of all the experts. A review of the literature on conventional and biological therapy previously collected by the participants was developed, and two teams were formed: the first would address everything related to conventional therapy in RA (HRCT) and the other, biological therapy in RA (TBAR). Three questionnaires related to the use of corticosteroids, HRCT and TBAR, were prepared, answered by the participants via email. In a second meeting, held in October 2016 in Havana, the analysis of all the responses provided was carried out. Questions with a response of 90% or more votes were considered as recommendations. Results: The questionnaires were answered by 95% of the participants. 9 recommendations and 1 algorithm were established. The recommendations are as follows: methotrexate is the drug of choice in the treatment of RA after diagnosis; The administration of another conventional drug (DMARDc) (azathioprine, salazosulfapyridine, antimalarials and leflunomide) is recommended in patients with a diagnosis of active RA in whom methotrexate is contraindicated or there is a failure in response - consider the administration of low doses of prednisone or equivalent (<7.5 mg/d) associated with DMARDc in patients with active moderate to severe RA, for the shortest possible time; perform serological control including tests for hepatitis B and C viruses and screening for HIV in all patients diagnosed with RA before starting treatment with DMARDc and biologics; in patients in remission or, at least, with a DAS-28 below 3.2, consideration should be given to withdrawing one of the DMARDs or reducing, to the minimum possible expression, the dose of both disease modifiers; if methotrexate fails, tocilizumab in combination with methotrexate or as monotherapy will be indicated. Conclusions: Aspects related to conventional therapy with methotrexate, azathioprine, salazosulfapyridine, antimalarials and leflunomide were agreed. The value of early diagnosis and immediate initiation of DMARDc therapy and the use of glucocorticoids was analyzed. Treatment with tocilizumab, the only biological available in Cuba against RA, will be administered when there is a failure in the response to conventional therapy and combinations between these drugs. It is recommended to hold educational conferences through the mass media aimed at patientshttp(AU)

Aberrantly low STAT3 and STAT5 responses are associated with poor outcome and an inflammatory gene expression signature in pediatric acute myeloid leukemia

The relapse rate for children with acute myeloid leukemia is nearly 40% despite aggressive chemotherapy and often stem cell transplant. We sought to understand how environment-induced signaling responses are associated with clinical response to treatment. We previously reported that patients whose AML cells showed low G-CSF-induced STAT3 activation had inferior event-free survival compared to patients with stronger STAT3 responses. Here, we expanded the paradigm to evaluate multiple signaling parameters induced by a more physiological stimulus. We measured STAT3, STAT5 and ERK1/2 responses to G-CSF and to stromal cell-conditioned medium for 113 patients enrolled on COG trials AAML03P1 and AAML0531. Low inducible STAT3 activity was independently associated with inferior event-free survival in multivariate analyses. For inducible STAT5 activity, those with the lowest and highest responses had inferior event-free survival, compared to patients with intermediate STAT5 responses. Using existing RNA-sequencing data, we compared gene expression profiles for patients with low inducible STAT3/5 activation with those for patients with higher inducible STAT3/5 signaling. Genes encoding hematopoietic factors and mitochondrial respiratory chain subunits were overexpressed in the low STAT3/5 response groups, implicating inflammatory and metabolic pathways as potential mechanisms of chemotherapy resistance. We validated the prognostic relevance of individual genes from the low STAT3/5 response signature in a large independent cohort of pediatric AML patients. These findings provide novel insights into interactions between AML cells and the microenvironment that are associated with treatment failure and could be targeted for therapeutic interventions (AU)

Mixed-methods study protocol: do national reporting and learning system medication incidents in palliative care reflect patient and carer concerns about medication management and safety?

INTRODUCTION: Approximately 20% of serious safety incidents involving palliative patients relate to medication. These are disproportionately reported when patients are in their usual residence when compared with hospital or hospice. While patient safety incident reporting systems can support professional learning, it is unclear whether these reports encompass patient and carer concerns with palliative medications or interpersonal safety. AIM: To explore and compare perceptions of (un)safe palliative medication management from patient, carer and professional perspectives in community, hospital and hospice settings. METHODS AND ANALYSIS: We will use an innovative mixed-methods study design combining systematic review searching techniques with cross-sectional quantitative descriptive analysis and interpretative qualitative metasynthesis to integrate three elements: (1) Scoping review: multiple database searches for empirical studies and first-hand experiences in English (no other restrictions) to establish how patients and informal carers conceptualise safety in palliative medication management. (2)Medication incidents from the England and Wales National Reporting and Learning System: identifying and characterising reports to understand professional perspectives on suboptimal palliative medication management. (3) Comparison of 1 and 2: contextualising with stakeholder perspectives. PATIENT AND PUBLIC INVOLVEMENT: Our team includes a funded patient and public involvement (PPI) collaborator, with experience of promoting patient-centred approaches in patient safety research. Funded discussion and dissemination events with PPI and healthcare (clinical and policy) professionals are planned. ETHICS AND DISSEMINATION: Prospective ethical approval granted: Cardiff University School of Medicine Research Ethics Committee (Ref 19/28). Our study will synthesise multivoiced constructions of patient safety in palliative care to identify implications for professional learning and actions that are relevant across health and social care. It will also identify changing or escalating patterns in palliative medication incidents due to the COVID-19 pandemic. Peer-reviewed publications, academic presentations, plain English summaries, press releases and social media will be used to disseminate to the public, researchers, clinicians and policy-makers.

Aberrantly low STAT3 and STAT5 responses are associated with poor outcome and an inflammatory gene expression signature in pediatric acute myeloid leukemia.

The relapse rate for children with acute myeloid leukemia is nearly 40% despite aggressive chemotherapy and often stem cell transplant. We sought to understand how environment-induced signaling responses are associated with clinical response to treatment. We previously reported that patients whose AML cells showed low G-CSF-induced STAT3 activation had inferior event-free survival compared to patients with stronger STAT3 responses. Here, we expanded the paradigm to evaluate multiple signaling parameters induced by a more physiological stimulus. We measured STAT3, STAT5 and ERK1/2 responses to G-CSF and to stromal cell-conditioned medium for 113 patients enrolled on COG trials AAML03P1 and AAML0531. Low inducible STAT3 activity was independently associated with inferior event-free survival in multivariate analyses. For inducible STAT5 activity, those with the lowest and highest responses had inferior event-free survival, compared to patients with intermediate STAT5 responses. Using existing RNA-sequencing data, we compared gene expression profiles for patients with low inducible STAT3/5 activation with those for patients with higher inducible STAT3/5 signaling. Genes encoding hematopoietic factors and mitochondrial respiratory chain subunits were overexpressed in the low STAT3/5 response groups, implicating inflammatory and metabolic pathways as potential mechanisms of chemotherapy resistance. We validated the prognostic relevance of individual genes from the low STAT3/5 response signature in a large independent cohort of pediatric AML patients. These findings provide novel insights into interactions between AML cells and the microenvironment that are associated with treatment failure and could be targeted for therapeutic interventions.

Production performance and nitrogen metabolism in dairy cows fed supplemental blends of rumen undegradable protein and rumen-protected amino acids in low- compared with high-protein diets containing corn distillers grains.

Feeding corn dried distillers grains with solubles (DDGS) in low crude protein (CP) diets could limit N waste in lactating cows. However, it also could possibly reduce metabolizable AA supply, especially Lys, and compromise milk production. Therefore, the objective of this study was to evaluate the effects of feeding supplemental blends of rumen undegradable protein (RUP) and rumen-protected (RP) AA in a low compared with high CP diet containing corn DDGS on milk production and selected measures of N utilization. Six multiparous Holstein cows (619.3 ± 49.8 kg of body weight; 26.8 ± 6.2 d in milk) were subjected to a split-plot, 3 × 3 Latin square design (21-d periods) with dietary CP content [low (14.6%; LP) or high (16.6%; HP)] as the whole-plot factor, and blend of RUP and RP-AA [control (CON), no supplement; blend A (0.11 kg/cow per d); or blend B (0.45 kg/cow per d)] as the sub-plot factor. All diets contained 10% corn DDGS; blends of RUP and RP-AA were top-dressed during morning feeding. There was no dietary CP content × supplemental blend interaction for all measured variables. Nutrient (dry matter, organic matter, neutral detergent fiber, acid detergent fiber, and CP), milk and milk component yields, and feed and apparent N efficiency did not differ for cows fed the low- compared with the high-protein diet. However, apparent total-tract CP digestibility, blood and milk urea-N concentrations, and urinary excretion (g/d) of N and urea-N were lower for cows fed the low-protein compared with the high-protein diet. There was no supplemental blend effect on nutrient intake and apparent total-tract digestibility, and milk and milk component yields. Except for a tendency for total urinary purine derivative excretion and microbial N flow to be lower for cows fed blend B compared with CON but not blend A, there was no supplemental blend effect on measures of N utilization. Both dietary CP content and supplemental blend of RUP and RP-AA had a marginal effect on the plasma free AA profile. In summary, reducing dietary CP content in diets containing corn DDGS had no effect on lactation performance, possibly accounting for the lack of a positive response following the provision of supplemental blends of RUP and RP-AA. However, reducing dietary CP content resulted in a decrease in blood and milk urea-N concentrations, and urinary excretion of N and urea-N, suggestive of an improvement in the efficiency of N use.

[A protocol for light therapy in bipolar disorder]. / Protocol voor lichttherapie bij bipolaire stoornis.

BACKGROUND: There is no national protocol for the use of light therapy in bipolar depression.
AIM: The chronotherapy collaboration group of the Foundation for Bipolar Disorders intended to write a protocol for light therapy in bipolar depressive episodes.
METHOD: Narrative review of several systematic reviews, two clinician's guides and deliberation with the sub-commission Guidelines of the Dutch Ophthalmologic Society.
RESULTS: The following indication was established: depressive episode, with or without seasonal features, in bipolar I or II disorder, including subsyndromal (depressive) seasonal complaints. The list of relative contra-indications (pre-existent retinal illnesses, systemic illnesses with effect on the retina and use of photosensitive medication) was shortened. In this case the medical professional discusses the possibility of an ophthalmologic consultation with the patient. Use of a mood stabilizer/antimanic medication in order to prevent mania or a mixed episode is only necessary in a depressive episode in bipolar I, but not in bipolar II disorder. Standard treatment is 10.000 lux white light during 30 minutes in the morning.
CONCLUSION: There is sufficient evidence to propose light therapy in a bipolar depressive episode with or without seasonal features.

Polyploidy affects the seed, dormancy and seedling characteristics of a perennial grass, conferring an advantage in stressful climates.

Polyploidy (the state of having more than two genome copies) is widely distributed in flowering plants and can vary within species, with polyploid races often associated with broad ecological tolerances. Polyploidy may influence within-species variation in seed development, germination and establishment. We hypothesized that interactions between polyploidy and the seed developmental environment would affect subsequent dormancy, germination and early growth traits, particularly in stressful environments. Using seeds developed in a common garden under ambient and warmed conditions, we conducted germination trials under drought and temperature stress, and monitored the subsequent growth of seedlings. The study species, Themeda triandra, is a widespread, keystone, Australian native grass and a known polyploid complex. Tetraploid plants produced heavier, more viable seeds than diploids. Tetraploids were significantly more dormant than diploids, regardless of seed developmental environment. Non-dormant tetraploids were more sensitive to germination stress compared to non-dormant diploids. Finally, tetraploid seedlings were larger and grew faster than diploids, usually when maternal plants were exposed to developmental temperatures atypical to the source environment. Seed and seedling traits suggest tetraploids are generally better adapted to stressful environments than diploids. Because tetraploid seeds of T. triandra are more dormant they are less likely to germinate under stress, and when they do germinate, seedling growth is rapid and independent of seed developmental environment. These novel results demonstrate that polyploidy, sometimes in interaction with developmental environment and possibly also asexuality, can have within-species variation in seed and seedling traits that increase fitness in stressful environments.