Motor abilities in adults born with very low birthweight: A study of two birth cohorts from Finland and Norway.

AIM: To compare overall, fine, and gross motor abilities in adults born preterm with very low birthweight (VLBW) and a control group of term-born individuals. METHOD: In a joint assessment of the Helsinki Study of Very Low Birth Weight Adults and NTNU Low Birth Weight in a Lifetime Perspective study, data were collected with harmonized methods for 118 adults born preterm (gestational age < 37 weeks) with VLBW (≤1500 g) and 147 control individuals. The primary outcome was overall motor abilities; secondary outcomes were fine and gross motor abilities. RESULTS: The Bruininks Motor Ability Test Short Form total score was 4.1 (95% confidence interval 2.7-6.0) points lower in adults born with VLBW than in the control group, adjusted for cohort, age, and sex. This was partly mediated by their shorter height. They also had lower scores for other fine and gross motor tests. Results were similar when participants with neurosensory impairment were excluded, and when we adjusted for additional covariates. INTERPRETATION: Adults born preterm with VLBW had poorer overall, fine, and gross motor abilities than adults born at term. This indicates that substantial difficulties in motor function among individuals born preterm with VLBW persist into mid-adulthood.

Carbon Footprint of Open Carpal Tunnel Release Surgery Performed in the Procedure Room Versus Operating Room Setting.

PURPOSE: Environmental sustainability is an important issue in health care because of large amounts of greenhouse gases attributable to hospitals. The operating room has been highlighted as one of the highest contributors, prompting several initiatives by organizations focused on the care of hand and upper extremity conditions. This study aimed to quantify and compare the carbon footprint of a common hand surgery in two different surgical settings, the procedure room (PR) and operating room. We hypothesized that open carpal tunnel release (oCTR) will generate a greater environmental impact in the operating room than in the PR. METHODS: This was a retrospective review of oCTRs performed at a tertiary care medical center. Current procedural technology codes isolated a single cohort of patients who underwent bilateral oCTR, one side performed in the PR and the contralateral side in the operating room. Current published emission conversions were used to calculate carbon footprint at our institution based on energy expenditure necessary for the creation and disposal of waste and sterilization of surgical equipment. Surgery time was combined with heating, ventilation and air conditioning/lighting energy consumption to estimate facility emissions. RESULTS: Fourteen patients had bilateral oCTR surgery performed in both settings. Open CTR performed in the operating room generated 3.7 kg more solid waste than when performed in the PR. In total, emissions from oCTR performed in the operating room generated 32.4 kg CO2, whereas oCTR in the PR emitted 13.0 kg CO2 per surgery. CONCLUSIONS: Performing a common hand procedure (oCTR) is more environmentally sustainable in the PR than in the operating room, with a 60% reduction in carbon footprint. CLINICAL RELEVANCE: Greater effort should be made to perform surgery in the PR instead of the operating room in appropriately indicated patients. Surgical sets should be evaluated for the necessity of included equipment and unnecessary waste.

Body composition in adults born preterm with very low birth weight.

BACKGROUND: Studies on body composition in preterm very low birth weight (VLBW < 1500 g) survivors are inconsistent and trajectories later in life unknown. We assessed body composition and its change from young to mid-adulthood in VLBW adults. METHODS: We studied 137 VLBW adults and 158 term-born controls from two birth cohorts in Finland and Norway at mean age 36 years. Body composition was assessed by 8-polar bioelectrical impedance. We compared results with dual-energy x-ray absorptiometry measurements at 24 years. RESULTS: In mid-adulthood, VLBW women and men were shorter than controls. Fat percentage (mean difference in women 1.1%; 95% CI, -1.5% to 3.5%, men 0.8%; -2.0% to 3.6%) and BMI were similar. VLBW women had 2.9 (0.9 to 4.8) kg and VLBW men 5.3 (2.7 to 8.1) kg lower lean body mass than controls, mostly attributable to shorter height. Between young and mid-adulthood, both groups gained fat and lean body mass (p for interaction VLBW x age>0.3). CONCLUSION: Compared with term-born controls, VLBW adults had similar body fat percentage but lower lean body mass, largely explained by their shorter height. This could contribute to lower insulin sensitivity and muscular fitness previously found in VLBW survivors and predispose to functional limitations with increasing age. IMPACT: In mid-adulthood, individuals born preterm with very low birth weight had similar body fat percentage but lower lean body mass than those born at term. This was largely explained by their shorter height. First study to report longitudinal assessments of body size and composition from young to mid-adulthood in very low birth weight adults. Lower lean body mass in very low birth weight adults could contribute to lower insulin sensitivity and muscular fitness and lead to earlier functional limitations with increasing age.

Assessment of complications associated with casting of acute distal radius fractures in adults.

PURPOSE: Controversy exists regarding the closed treatment of distal radius fractures. Circumferential casting of acute distal radius fractures has been shown to be safe in children, however, little research has demonstrated its safety in adults. The purpose of this study was to assess the risk of complications associated with casting acute distal radius fractures in adult patients. METHODS: Patients with a distal radius fracture treated by a single hand surgeon at a level 1 trauma center were retrospectively reviewed over a 3-year period. Patients were evaluated in the emergency room and were provisionally immobilized either with short-arm fiberglass casts or with splints. Patients were followed for a minimum of 4 weeks. Complication rates associated with casting were recorded, including rates of compartment syndrome and acute carpal tunnel syndrome. RESULTS: Eighty-one patients were included in this study. A total of 30 patients met inclusion criteria for placement of a short arm cast in the Emergency Department. Mean patient age was 63.2 years. The majority of patients sustained their injuries from a ground level fall. A minority of patients had radiographic evidence of intra-articular extension or underwent a reduction prior to casting. There were no patients who developed compartment syndrome or acute carpal tunnel syndrome as a result from the casting. The majority of patients did not require a cast change for at least 4 weeks. None of our patients went on to surgery. CONCLUSION: There were no major complications associated with casting of acute, low energy distal radius fractures in this series of 30 adult patients. While further studies with larger numbers of patients are necessary to establish safety of casting, this study suggests that casting may be a safe and effective treatment for low-energy distal radius fractures in adult patients presenting with a normal neurovascular exam. TYPE OF STUDY/LEVEL OF EVIDENCE: Retrospective comparative study, Level III.

Delayed cortical processing of auditory stimuli in children with autism spectrum disorder: A meta-analysis of electrophysiological studies.

Several researchers have hypothesised that individuals with Autism Spectrum Disorder (ASD) show encoding delays in their obligatory event-related potentials (ERPs)/ event-related fields (ERFs) for low-level auditory information compared to neurotypical (NT) samples. However, empirical research has yielded varied findings, such as low-level auditory processing in ASD samples being unimpaired, superior, or impaired compared to NT samples. Diverse outcomes have also been reported for studies investigating ASD-NT differences in functional lateralisation of delays. The lack of consistency across studies has prevented a comprehensive understanding of the overall effects in the autistic population. Therefore, this meta-analysis compared long-latency ERPs and ERFs produced by autistic and NT individuals to non-linguistic auditory stimuli to test, firstly, the robustness of auditory processing differences and, secondly, whether these differences are observed in one or both hemispheres. Nine articles meeting the inclusion criteria were included in the meta-analysis. Meta-analytic results indicated that autistic individuals demonstrate bilaterally delayed P1/ M50 peaks and lateralised delays in the right but not left hemisphere N1/ M100 peak. These results further inform our understanding of auditory processing and lateralisation across the autism spectrum.

CTG repeat-targeting oligonucleotides for down-regulating Huntingtin expression.

Huntington's disease (HD) is a fatal, neurodegenerative disorder in which patients suffer from mobility, psychological and cognitive impairments. Existing therapeutics are only symptomatic and do not significantly alter the disease progression or increase life expectancy. HD is caused by expansion of the CAG trinucleotide repeat region in exon 1 of the Huntingtin gene (HTT), leading to the formation of mutant HTT transcripts (muHTT). The toxic gain-of-function of muHTT protein is a major cause of the disease. In addition, it has been suggested that the muHTT transcript contributes to the toxicity. Thus, reduction of both muHTT mRNA and protein levels would ideally be the most useful therapeutic option. We herein present a novel strategy for HD treatment using oligonucleotides (ONs) directly targeting the HTT trinucleotide repeat DNA. A partial, but significant and potentially long-term, HTT knock-down of both mRNA and protein was successfully achieved. Diminished phosphorylation of HTT gene-associated RNA-polymerase II is demonstrated, suggestive of reduced transcription downstream the ON-targeted repeat. Different backbone chemistries were found to have a strong impact on the ON efficiency. We also successfully use different delivery vehicles as well as naked uptake of the ONs, demonstrating versatility and possibly providing insights for in vivo applications.

Domestic gardens and self-reported health: a national population study.

BACKGROUND: There is a growing recognition of the health benefits of the natural environment. Whilst domestic gardens account for a significant proportion of greenspace in urban areas, few studies, and no population level studies, have investigated their potential health benefits. With gardens offering immediate interaction with nature on our doorsteps, we hypothesise that garden size will affect general health-with smaller domestic gardens associated with poorer health. METHODS: A small area ecological design was undertaken using two separate analyses based on data from the 2001 and 2011 UK census. The urban population of England was classified into 'quintiles' based on deprivation (Index of Multiple Deprivation) and average garden size (Generalised Land Use Database). Self-reported general health was obtained from the UK population census. We controlled for greenspace exposure, population density, air pollution, house prices, smoking, and geographic location. Models were stratified to explore the associations. RESULTS: Smaller domestic gardens were associated with a higher prevalence of self-reported poor health. The adjusted prevalence ratio of poor self-reported general health for the quintile with smallest average garden size was 1.13 (95% CI 1.12-1.14) relative to the quintile with the largest gardens. Additionally, the analysis suggested that income-related inequalities in health were greater in areas with smaller gardens. The adjusted prevalence ratio for poor self-reported general health for the most income deprived quintile compared against the least deprived was 1.72 (95% CI 1.64-1.79) in the areas with the smallest gardens, compared to 1.31 (95% CI 1.21-1.42) in areas with the largest gardens. CONCLUSIONS: Residents of areas with small domestic gardens have the highest levels of poor health/health inequality related to income deprivation. Although causality needs to be confirmed, the implications for new housing are that adequate garden sizes may be an important means of reducing socioeconomic health inequalities. These findings suggest that the trend for continued urban densification and new housing with minimal gardens could have adverse impacts on health.

High Early Major Complication Rate After Revision for Mechanically Assisted Crevice Corrosion in Metal-on-Polyethylene Total Hip Arthroplasty.

BACKGROUND: Failed total hip arthroplasty caused by mechanically assisted crevice corrosion (MACC) has serious consequences such as adverse local tissue reaction. Revision is currently indicated for significant hip pain, stiffness, and dysfunction; hip instability; progressive bone loss; and soft tissue destruction. Outcomes of this revision surgery are not yet completely understood. METHODS: We examined the surgical outcomes at a minimum of 6 months (average, 25; range, 7-68 months) in a cohort of 27 consecutive patients who underwent revision total hip arthroplasty for MACC associated with a single implant vendor and taper type. RESULTS: Major orthopedic complications occurred in 7 of 27 patients (25.9%), each after the original revision surgery. Five additional major complications occurred in subsequent surgeries. Postoperative hip dislocation occurred in 6 of 27 (22.2%), deep infection occurred in 3 of 27 (11.1%), and aseptic acetabular loosening, seroma requiring irrigation and debridement, pulmonary embolism, periprosthetic fracture, and reintubation each occurred in 1 of 27 (3.7%). Harris hip scores improved significantly with surgery (P = .0002), but overall, scores were lower for those who had major complications (70.9 vs 89.2), and only 20 of 27 patients (74.1%) had good or excellent outcomes. CONCLUSION: Symptomatic MACC is a potentially devastating diagnosis, because of decreased soft tissue and bone viability associated with adverse local tissue reaction. This leads to a high early major complication rate.

High-Throughput Discovery of Aptamers for Sandwich Assays.

Sandwich assays are among the most powerful tools in molecular detection. These assays use "pairs" of affinity reagents so that the detection signal is generated only when both reagents bind simultaneously to different sites on the target molecule, enabling highly sensitive and specific measurements in complex samples. Thus, the capability to efficiently screen affinity reagent pairs at a high throughput is critical. In this work, we describe an experimental strategy for screening "aptamer pairs" at a throughput of 106 aptamer pairs per hour-which is many orders of magnitude higher than the current state of the art. The key step in our process is the conversion of solution-phase aptamers into "aptamer particles" such that we can directly measure the simultaneous binding of multiple aptamers to a target protein based on fluorescence signals and sort individual particles harboring aptamer pairs via the fluorescence-activated cell-sorter instrument. As proof of principle, we successfully isolated a high-quality DNA aptamer pair for plasminogen activator inhibitor 1 (PAI-1). Within only two rounds of screening, we discovered DNA aptamer pairs with low-nanomolar sensitivity in dilute serum and excellent specificity with minimal off-target binding even to closely related proteins such as PAI-2.

Improvement of a streptavidin-binding aptamer by LNA- and α-l-LNA-substitutions.

Forty modified versions of a streptavidin-binding aptamer each containing single or multiple LNA or α-l-LNA-substitutions were synthesized and their dissociation constants determined by surface plasmon resonance experiments. Both full-length and truncated versions of the aptamer were studied and compared with the unmodified DNA aptamers. A ∼two-fold improvement in binding affinity was achieved by incorporation of LNA nucleotides in the 3'-part of the stems of the streptavidin-binding aptamer whereas LNA- and α-l-LNA-substitutions in the terminal stem increased the serum stability.

Developing an innovative 3D printing platform for production of personalised medicines in a hospital for the OPERA clinical trial.

Breast cancer is the most frequently diagnosed cancer in women worldwide, and non-adherence to adjuvant hormonotherapy can negatively impact cancer recurrence and relapse. Non-adherence is associated with side effects of hormonotherapy. Pharmacological strategies to mitigate the side effects include coadministration of antidepressants, however patients remain non-adherent. The aim of this work was to develop medicines containing both hormonotherapy, tamoxifen (20 mg), along with anti-depressants, either venlafaxine (37.5 or 75 mg) or duloxetine (30 or 60 mg), to assess the acceptability and efficacy of this personalised approach for mitigating tamoxifen side effects in a clinical trial. A major criterion for the developed medicines was the production rate, specified at minimum 200 dosage units per hour to produce more than 40,000 units required for the clinical trial. A novel capsule filling approach enabled by the pharmaceutical 3D printer M3DIMAKER 2 was developed for this purpose. Firstly, semi-solid extrusion 3D printing enabled the filling of tamoxifen pharma-ink prepared according to French compounding regulation, followed by filling of commercial venlafaxine or duloxetine pellets enabled by the development of an innovative pellet dispensing printhead. The medicines were successfully developed and produced in the clinical pharmacy department of the cancer hospital Gustave Roussy, located in Paris, France. The developed medicines satisfied quality and production rate requirements and were stable for storage up to one year to cover the duration of the trial. This work demonstrates the feasibility of developing and producing combined tamoxifen medicines in a hospital setting through a pharmaceutical 3D printer to enable a clinical trial with a high medicines production rate requirement.

Foveal thickness and its association with visual acuity in adults born preterm with very low birth weight: A two-country birth cohort study.

PURPOSE: To explore foveal and parafoveal thickness in adults born preterm with very low birth weight (VLBW) and its association with best-corrected visual acuity (BCVA) and gestational age (GA) compared to adults born at term. METHODS: In a joint study of the Helsinki Study of Very Low Birth Weight Adults (Finland) and the NTNU Low Birth Weight Life study (Norway), 106 VLBW and 143 term-born controls were examined with spectral-domain optical coherence tomography and BCVA at age 31-43 years. Thickness of retinal layers was segmented in the foveal and parafoveal areas of the macula. RESULTS: The total retinal thickness in the foveal area was thicker in VLBW adults compared with controls; mean (SD): 292.5 µm (28.2) and 272.4 µm (20.2); p < 0.001, and thinner in the parafoveal areas of the macula. These findings could be explained by a thicker inner retinal layer in the foveal area found in VLBW adults compared with controls (mean difference 20.4 µm; CI: 15.0 to 25.9), where a thicker fovea was associated with lower GA, but not BCVA. CONCLUSION: Adults born preterm with VLBW had a thicker retina in the foveal area than controls and this was associated with GA, but not with BCVA. These changes seem to be related to a thicker inner retinal layer in VLBW adults. The findings imply that signs of macular underdevelopment are still present in adulthood, but not necessarily related to reduced visual function.

Visual function in adults born preterm with very low birth weight-A two-country birth cohort study.

PURPOSE: The purpose of the study was to investigate visual function and vision-related general health in adults that were born preterm with very low birth weight (VLBW: birth weight < 1500 g) in their 30s-40s. METHODS: We recruited 137 adults born preterm with VLBW and 158 term-born controls aged 31-43 years from two birth cohorts: the Helsinki Study of Very Low Birth Weight Adults (Finland) and the NTNU Low Birth Weight in a Lifetime Perspective study (Norway). We used neonatal data and measured refraction, best-corrected visual acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, contrast sensitivity, visual fields, intraocular pressure (IOP), self-reported vision-targeted health status with the National Eye Institute Visual Function Questionnaire-25. RESULTS: VLBW adults had a lower BCVA ETDRS score than controls: mean (SD) better eye 86.7 (13.4) versus 90.2 (4.4), p = 0.02; mean (SD) worse eye 82.3 (14.9) versus 87.6 (4.6), p = 0.003. VLBW adults also had lower contrast sensitivity thresholds in several spatial frequencies and scored lower than controls in eight out of the 12 subscales of self-reported vision-targeted health status. Refraction, visual fields and IOP were similar between groups. Two VLBW participants were blind. None had been treated for retinopathy of prematurity. CONCLUSION: We suggest that lower visual function and vision-related health represent life-long consequences of prematurity and VLBW in the studied 31- to 43-year-old cohort. The underlying mechanisms remain to be determined.

Visual outcomes and their association with grey and white matter microstructure in adults born preterm with very low birth weight.

Individuals born with very low birth weight (VLBW; < 1500 g) have a higher risk of reduced visual function and brain alterations. In a longitudinal cohort study, we assessed differences in visual outcomes and diffusion metrics from diffusion tensor imaging (DTI) at 3 tesla in the visual white matter pathway and primary visual cortex at age 26 in VLBW adults versus controls and explored whether DTI metrics at 26 years was associated with visual outcomes at 32 years. Thirty-three VLBW adults and 50 term-born controls was included in the study. Visual outcomes included best corrected visual acuity, contrast sensitivity, P100 latency, and retinal nerve fibre layer thickness. Mean diffusivity, axial diffusivity, radial diffusivity, and fractional anisotropy was extracted from seven regions of interest in the visual pathway: splenium, genu, and body of corpus callosum, optic radiations, lateral geniculate nucleus, inferior-fronto occipital fasciculus, and primary visual cortex. On average the VLBW group had lower contrast sensitivity, a thicker retinal nerve fibre layer and higher axial diffusivity and radial diffusivity in genu of corpus callosum and higher radial diffusivity in optic radiations than the control group. Higher fractional anisotropy in corpus callosum areas were associated with better visual function in the VLBW group but not the control group.

Social Support: The Effect on Nocturnal Blood Pressure Dipping.

Social support has long been associated with cardiovascular disease risk assessed with blood pressure (BP). BP exhibits a circadian rhythm in which BP should dip between 10 and 15% overnight. Blunted nocturnal dipping (non-dipping) is a predictor of cardiovascular morbidity and mortality independent of clinical BP and is a better predictor of cardiovascular disease risk than either daytime or nighttime BP. However, it is often examined in hypertensive individuals and less often in normotensive individuals. Those under age 50 are at increased risk for having lower social support. This study examined social support and nocturnal dipping in normotensive individuals under age 50 using ambulatory blood pressure monitoring (ABP). ABP was collected in 179 participants throughout a 24-h period. Participants completed the Interpersonal Support Evaluation List, which assesses perceived levels of social support in one's network. Participants with low levels of social support demonstrated blunted dipping. This effect was moderated by sex, with women showing greater benefit from their social support. These findings demonstrate the impact social support can have on cardiovascular health, exhibited through blunted dipping, and are particularly important as the study was conducted in normotensive individuals who are less likely to have high levels of social support.

Advancing non-destructive analysis of 3D printed medicines.

Pharmaceutical 3D printing (3DP) has attracted significant interest over the past decade for its ability to produce personalised medicines on demand. However, current quality control (QC) requirements for traditional large-scale pharmaceutical manufacturing are irreconcilable with the production offered by 3DP. The US Food and Drug Administration (FDA) and the UK Medicines and Healthcare Products Regulatory Agency (MHRA) have recently published documents supporting the implementation of 3DP for point-of-care (PoC) manufacturing along with regulatory hurdles. The importance of process analytical technology (PAT) and non-destructive analytical tools in translating pharmaceutical 3DP has experienced a surge in recognition. This review seeks to highlight the most recent research on non-destructive pharmaceutical 3DP analysis, while also proposing plausible QC systems that complement the pharmaceutical 3DP workflow. In closing, outstanding challenges in integrating these analytical tools into pharmaceutical 3DP workflows are discussed.

"I Just Want to be Acknowledged": Suicidal Ideation Experiences among Sexual Minority Students at a Religiously Affiliated University.

Research finds that sexual minority university students experience considerable psychological and emotional distress. Furthermore, a recent study at Brigham Young University (BYU)-a university affiliated with The Church of Jesus Christ of Latter-day Saints-found that suicidality prevalence and severity were twice as high among sexual minority students compared to their heterosexual peers. To better understand this finding, we interviewed ten sexual minority students at BYU who reported clinically significant current or previous suicidality. A coding team and auditors then analyzed and categorized the transcripts of these interviews using the Consensual Qualitative Research methodology. Five domains emerged related to suicidality among sexual minority students: deterrents from suicidal ideation and intent; contributors to suicidal ideation and intent; religious and spiritual experiences; experiences with BYU; and suggested improvements. We found patterns consistent with previous literature, including relational and belonging factors contributing to suicidality; we also found that certain doctrinal interpretations were related to increased suicidality. The primary improvement requested by participants was feeling better understood and accepted (rather than ignored or marginalized). We discuss study limitations (including small sample size and low generalizability,), future directions for research, and implications for religious university campuses.

Large scale synthesis of 2'-amino-LNA thymine and 5-methylcytosine nucleosides.

Thymine intermediate 17 has been synthesized on a multigram scale (50 g, 70 mmol) from starting sugar 1 in 15 steps in an overall yield of 73%, with only 5 purification steps. The key thymine intermediate 18 was obtained from 17 in a single step in 96% yield, whereas the key 5-methylcytosine intermediate 20 was obtained from 17 in 2 steps in 58% yield. This highly efficient large scale route necessitates only 2 and 3 novel steps to obtain N2'-functionalized thymine and 5-methylcytosine amino-LNA phosphoramidites from these key intermediates, respectively.

Three pyrene-modified nucleotides: synthesis and effects in secondary nucleic acid structures.

Synthesis of three pyrene-modified nucleosides was accomplished using the CuAAC reaction. Hereby, pyrene is attached either to the 5'-position of thymidine or to the 2'-position of 2'-deoxyuridine through triazolemethylene linkers, or to the 2'-position of 2'-deoxyuridine through a more rigid triazole linker. The three nucleosides were incorporated into oligonucleotides, and these were combined in different duplexes and other secondary structures, which were analyzed by thermal stability and fluorescence studies. The three monomers were found to have different impacts on the nucleic acid complexes. Hence, pyrene attached to the 5'-position shows a tendency for intercalation into the duplex as indicated by a general decrease in fluorescence intensity followed by an increase in duplex thermal stability. Pyrene attached to the 2'-position through a rigid triazole linker also shows a tendency for intercalation but with decrease in duplex stability, whereas the pyrene attached to the 2'-position through a triazolemethylene linker is primarily situated in the minor groove as indicated by an increase in fluorescence but here in most cases leading to increase in duplex stability. All three pyrene nucleotides lead to thermal stabilization of bulged duplexes and three-way junctions. In some cases when two pyrenes were introduced into the core of these complexes, the formation or disappearance of a fluorescence excimer band can be used to indicate the hybridization process. Hereby these oligonucleotides can act as specific recognition probes.

The influence of thermal history on the physical behavior of poly(ethylene glycol) (PEG).

OBJECTIVES: To investigate the influence of thermal history on the physical behavior of poly(ethylene glycol) (PEG), commonly used as a pharmaceutical excipient. MATERIALS AND METHODS: Rheological investigations together with SEM imaging and solid state analysis by XRPD and DSC were used to characterize PEG as starting material, as well as PEG:lactose monohydrate granules. For granulation experiments PEG 6000 was used and for further investigations of physicochemical properties, three M(w) of PEG (3000-10000) with different thermal histories obtained by melting the PEG followed by solidification with specific cooling rates. RESULTS AND DISCUSSION: More uniform granules were obtained when fast cooled PEG was used as binder. XRPD suggested similar crystallinity for the different M(w) and thermal history did not influence the results drastically. However, rheological analysis and DSC measurements indicated different melting behavior dependent on the M(w) of PEG. PEG 6000 and 10000 were affected by the thermal treatment where stepwise melting was observed with slower cooling rate probably due to increased formation of extended structures. CONCLUSIONS: Increased cooling rate gives rise to increased randomness, more folded structure of PEG, which reflects in the outcome of the granulation process.