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Background: Storage of whole blood (WB) for less than 24 hours at ambient temperature is permitted in Europe, but data directly comparing storage with and without active cooling are lacking, which was investigated and compared to current standard methods. Study Design and Methods: WB was stored in one of four different ways for 24 hours after donation before processing on Day 1 to red cell concentrates (RCCs) in saline-adenine-glucose-mannitol and fresh-frozen plasma (FFP; n = 20 each): 1) at 22 degrees C in plastic trays, 2) in cooling devices (Compocool II, NPBI), 3) at 4 degrees C, or 4) processed from WB without storage less than 8 hours from donation (Day 0). Results: 2,3-Diphosphoglycerate (2,3-DPG) in RCCs were lower after ambient storage compared with those processed on Day 0 or after 4 degrees C storage. Rapid cooling slowed the loss of 2,3-DPG but levels were undetectable by Day 21 with any method. On Day 42 of RCC storage, there was no significant difference between storage methods in levels of adenosine triphosphate or hemolysis. Potassium levels were lower in RCCs from WB stored at ambient compared with those produced on Day 0, regardless of the use of cooling plates. FFP produced from WB on Day 0 or after storage at ambient with or without active cooling met UK specifications (>75% of units >0.70 IU/mL Factor VIII). Conclusion: These data suggest that RCCs and FFP produced from WB that has been stored at ambient temperature with or without active cooling are of acceptable quality compared with those produced using current standard methods in the United Kingdom. [ABSTRACT FROM AUTHOR]

Age differences in autonomic nervous system response patterns were investigated to determine if there was an age-related increase in the tendency to respond to multiple stimuli with a consistent response hierarchy (individual consistency). Five stimuli were administered in a Latin Square design-mental arithmetic, cold pressor, isometric exercise, comic slide, and time estimation. A warning tone was presented before each stimulus. Physiological measures included heart rate, systolic and diastolic blood pressures, skin potential, breathing rate, and digital blood flow. To compare responses in different systems, responses were standardized according to the formula, Z = [50 + 10(X - M)]/σ, where Z is the standardized score, X is the difference between stimulation and warning levels, M is the avenge response for that system, and σ is the square root of the mean square for error from the analysis of variance computed for each response system. A matrix was generated lot each subject which Included his Z scores from the six response systems for the five stimuli. Intraclass correlations were then computed. Individual consistency significantly Increased with increasing age (r = .33, p<.005). [ABSTRACT FROM AUTHOR]

Introduction As part of the process to improve the safety and quality of the platelet supply, the NBS is evaluating the use of platelet storage media (PSM). The objective of this study was to produce a platelet concentrate (PC) containing 70% SSP+ and 30% plasma, whilst maintaining platelet yield, and to evaluate their in vitro function. Study Design. Buffy coats were prepared using the standard NBS method and four (ABO matched) were pooled together with 250 mL of SSP+. Centrifugation was performed using optimised conditions for PSM and an Optipress used to express the PC through a Pall Autostop LD filter into a Pall ELX storage bag. Ten PCs were prepared, and platelet quality was assessed using in vitro assays for functionality and activation on days 1, 5, 7 and 9 of storage. Results The assay results were compared to platelets stored in 100% plasma from a previous study. Conclusion Buffy coat derived PC in 70% SSP+ met the required specifications for platelet yield, residual leucocyte count, pH and volume. Platelet activation was lower in PCs stored in SSP+ and units stored in SSP+ maintain acceptable in vitro function during storage. [ABSTRACT FROM AUTHOR]

Background The Atreus 2C+ system automates whole blood (WB) processing into a red cell concentrate, plasma and buffy coat (BC) suitable for platelet concentrate (PC) manufacture. This study compared the quality of PC made from BC using the Atreus, with those made by a manual method. Study design and methods WB was collected into Atreus disposables or standard bottom and top processing packs and held without active cooling for 26 h at 22 ± 2°C before processing, either with the Atreus, or using a centrifuge and press. BC were rested for 3 h and then 4 BC were pooled with one unit of plasma, mixed, centrifuged and pressed to make a pooled PC. The PC were analysed for quality markers to day 9 of storage. Results Platelet quality was good in both Atreus 2C+ derived PC and control units throughout storage. Metabolic markers (pH, ATP and HSR) and activation markers (CD62P, sCD62P, annexin V binding, microparticles, GP IIb/IIIa) did not differ between the Atreus and control units. Atreus-derived PC had significantly lower platelet yields (302 ± 59 × 109 platelets/unit; mean ± standard deviation, n = 8) than control PC (411 ± 76 × 109 platelets/unit; P < 0·01), but met the UK guidelines for platelet yield Conclusion From these in vitro data, PC produced from buffy coats prepared using the Atreus appear suitable for clinical use, and WB may be held at ambient temperature overnight without the use of active cooling devices. Optimizing the secondary processing conditions to handle Atreus 2C+ derived BC may increase the platelet yield. [ABSTRACT FROM AUTHOR]

Background and Objectives The aim of the study was to compare the in vitro quality of buffy coat-derived platelet concentrates (PC) during extended storage in plasma or additive solution in three different storage bags. Materials and Methods A pooled and split design was chosen so that identical PCs were produced in either 100% plasma, 70% PASII : 30% plasma or 70% CompoSol : 30% plasma ( n = 6 each). This was repeated for three different manufacturers’ platelet storage bags (Fresenius, Baxter and Pall). PCs were sampled on days 1, 5, 7 and 9 of storage and tested in vitro using a variety of tests of platelet function. For each bag type, storage in PASII or Composol was compared with plasma (data taken across the entire storage period), and differences occurring with time were analysed for all storage media. Results The pH of all PCs was > 6·8 at day 9 of storage. In vitro platelet function, as assessed by markers of platelet activation and metabolism, of PCs stored in CompoSol appeared to be similar to that of PCs stored in plasma over 9 days of storage. In contrast, PCs stored in PASII tended to have significantly higher levels of platelet activation (almost a twofold increase in % platelets positive for CD62P by day 5) and lower hypotonic shock response (approximately 40%, by day 7) compared to either PCs stored in 100% plasma or 70% CompoSol. The magnitude of the differences observed between platelet storage media appeared to be dependent on the type of platelet storage bag with the highest degree of platelet activation and lowest hypotonic shock response values being observed in Fresenius bags in combination with PASII. Conclusions The maintenance of platelet function in vitro during extended storage of PCs in platelet additive solutions is dependent on the combination of type of additive solution and type of platelet storage bag. For all bag types studied, storage in PASII resulted in poorer platelet function in vitro. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the quality of leucodepleted (LD) fresh-frozen plasma (FFP) produced using one of five whole blood filters (Baxter RS2000 & RZ2000, NPBI T2926, Macopharma LST1 and Terumo WBSP) or two plasma filters (Pall LPS1 and Baxter FGR7014). Whole blood or plasma was filtered within 8 h of collection at an ambient temperature. Samples were taken pre- and post filtration for analysis of coagulation factors and complement activation (n = 7–12 for each type of filter). All filtered units (209–286 ml) contained < 5 × 106 residual leucocytes and < 30 × 109/l platelets. Statistically significant losses of factors V, VIII, IX, XI and XII and increases in markers of coagulation activation were observed (0–21%), which were dependent on filter type. None of the filters had a significant effect on von Willebrand factor (VWF) multimeric distribution or the activity of VWF and factors II, VII or X. The effect on levels of C3a appeared to be related to the filter surface charge: positively charged filters resulted in C3a generation, whereas negatively charged resulted in C3a removal. None of the observed changes are likely to be clinically significant unless subsequent processing of plasma (such as pathogen inactivation) results in further losses of coagulation factors. [ABSTRACT FROM AUTHOR]

Highlights: [•] Evaluation of MRS as an outcome measure for detecting disease modification. [•] Passive immunization in transgenic mouse model of Alzheimer’s disease. [•] Treatment effect detected by MRS with myo-inositol reduction. [•] MRS shown to be a valid in vivo measure of anti-Aβ therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Abstract: Our laboratory and others have reported the ability to detect individual Alzheimer''s disease (AD) amyloid plaques in transgenic mouse brain in vivo by magnetic resonance imaging (MRI). Since amyloid plaques contain iron, most MRI studies attempting to detect plaques in AD transgenic mouse brain have employed techniques that exploit the paramagnetic effect of iron and have had mixed results. In the present study, using five-way anatomic spatial coregistration of MR images with three different histological techniques, properties of amyloid plaques in AD transgenic mouse brain were revealed that may explain their variable visibility in gradient- and spin-echo MR images. The results demonstrate differences in the visibility of plaques in the cortex and hippocampus, compared to plaques in the thalamus, by the different MRI sequences. All plaques were equally detectable by T 2 SE, while only thalamic plaques were reliably detectable by T 2*GE pulse sequences. Histology revealed that cortical/hippocampal plaques have low levels of iron while thalamic plaques have very high levels. However, the paramagnetic effect of iron does not appear to be the sole factor leading to the rapid decay of transverse magnetization (short T 2) in cortical/hippocampal plaques. Accordingly, MRI methods that rely less on iron magnetic susceptibility effect may be more successful for eventual human AD plaque MR imaging, particularly since human AD plaques more closely resemble the cortical and hippocampal plaques of AD transgenic mice than thalamic plaques. [Copyright &y& Elsevier]

This longitudinal study on 94 families examined the extent to which parent sensitivity, infant affect, and affect regulation at 4 months predicted mother-infant and father-infant attachment classifications at 1 year. Parent sensitivity was rated from face-to-face interaction episodes; infant affect and regulatory behaviors were rated from mother-infant and father-infant still-face episodes at 4 months. Infants' attachment to mothers and fathers was rated from the Strange Situation at 12 and 13 months. MANOVAs indicated that 4-month parent and infant factors were associated with infant-mother but not infant-father attachment groups. Discriminant Function Analysis further indicated that two functions, "Affect Regulation" and "Maternal Sensitivity," discriminated infant-mother attachment groups; As and B1-B2s showed more affect regulation toward mothers and fathers than B3-B4s and Cs at 4 months, and mothers of both secure groups were more sensitive than mothers of Cs. Finally, the association between maternal sensitivity and infant-mother attachment was partially mediated by infant affect regulation. [ABSTRACT FROM AUTHOR]

Background: In addition to classic midbrain pathology, Parkinson's disease (PD) is accompanied by changes in pontine and medullary brainstem structures. These additional abnormalities may underlie non-motor features as well as play a role in motor disability.Methods: Using novel magnetic resonance imaging (MRI) methods based on rotating frame adiabatic R(1ρ) (i.e., measurements of longitudinal relaxation during adiabatic full passage pulses) and modified magnetization transfer (MT) MRI mapping, we sought to identify brainstem alterations in nine individuals with mild-moderate PD (off medication) and ten age-matched controls at 4 T.Results: We discovered significant differences in MRI parameters between midbrain and medullary brainstem structures in control subjects as compared to PD patients.Conclusions: These findings support the presence of underlying functional/structural brainstem changes in mild-moderate PD. [ABSTRACT FROM AUTHOR]

PURPOSE: We have previously reported results of a pilot study in patients with locally advanced breast cancer receiving primary systemic chemotherapy (PST) showing that a decrease in tumor choline concentration ([tCho]) measured one day after starting treatment was associated with clinical response based on MRI. In this follow-up study with a larger cohort, we assessed whether early changes in [tCho] were associated with clinical response, based on both MRI and pathology, and survival. METHODS AND MATERIALS: Women with locally advanced breast cancer scheduled for PST were scanned using a high-field MRI/MRS protocol prior to treatment, day 1 after treatment, and at the end of the first course of chemotherapy. MRI/MRS was performed on a 4 T Varian system with unilateral transmit/receive breast coils. MRI consisted of contrast-enhanced T1-weighted 3D gradient echo scans with one-minute temporal resolution. A single-voxel MR spectrum was acquired from the index lesion after MRI, and the concentration of total choline compounds ([tCho]) was quantified using water as an internal reference. Clinical response was assessed using RECIST criteria for measuring the longest diameter (LD) of the index lesion, and by pathologic complete response (pCR) at definitive surgery. Overall survival (OS) and invasive disease free survival (IDFS) were assessed by retrospective review of clinical records and the social security death index. The associations of change in [tCho] with pCR/LD response and with IDFS/OS were assessed using logistic/Cox regression, respectively, adjusted for node positivity and pCR status. RESULTS: Of the 74 women enrolled in the trial, 51 women (ages 28-71, median 47 years) were scanned at all time points and included in the final analysis. Of these, 17 subjects had a partial or complete imaging RECIST response based on a ≥30% decrease of the LD of the index lesion. Pathologic complete response, defined as no detectable invasive disease in the breast, was observed in 13/51 overall subjects and in 6/35 hormone receptor positive (ER+ or PR+) subjects. Median follow-up time for survival analysis was 64 months (range 11-102 months). Linear models showed no significant association between change in [tCho] and either pCR or RECIST response. An increase in [tCho] between the pretreatment scan and day 1 after treatment was found to be associated with reduced likelihood of both OS and IDFS. We found no association between pCR status and either OS or IDFS when considering all subjects and in the HR+ cohort (see Table 1). No results could be reported for the HR- group (14 subjects) due to an insufficient number of events. CONCLUSION: Compared to our previous study, we did not confirm that changes in [tCho] were associated with RECIST responses. However, increased MRS-measured [tCho] after 1 day of treatment was associated with reduced OS and IDFS independent of pCR. We conclude that increases in [tCho] might be a negative predictor of chemotherapy benefit. [ABSTRACT FROM AUTHOR]

Introduction The Gambro OrbiSac device is designed to automate the preparation of platelet concentrates (PC) from buffy coats (BC). The aim of this study was to evaluate the in vitro function of PC produced using the OrbiSac system and stored in plasma. Study design Ten PC were produced by automated pooling of four ABO matched BC and a single unit of plasma. The ring-shaped pooling bag was centrifuged and the platelet rich supernatant automatically expressed, through a leucodepletion filter, into a Gambro ELP storage bag. All PC were stored at 22°C with agitation and sampled on days 1, 5, 7 and 9. Samples were evaluated for platelet count and standard markers of platelet quality. The assay results were compared to platelets produced by manual methods and stored in a Pall ELX bag in a previous study. Results Hypotonic shock response (HSR) values were found to be significantly lower in this study when compared to manually produced PC. This was due to increased red cell contamination in these units. HSR was further investigated during a larger scale trial and all units ( n = 25) showed improved day 1 values (78%, range: 61–93%). Values from these additional PC were comparable with those from manually produced PC. Conclusion PC produced with the OrbiSac system achieved the local specification for platelet count. However, these units were higher in volume than those produced by manual methods, with 70% of units exceeding the locally specified maximum volume of 350 mL. This problem could be addressed during later trials. OrbiSac PC have acceptable pH, blood gases, HSR levels and platelet activation markers and results are broadly comparable to data generated in a previous study of manually produced PC. These results suggest that platelets produced with the Gambro OrbiSac system are comparable to those produced using the current manual methods. [ABSTRACT FROM AUTHOR]