Law Reform in Estonia: The Role of Georgetown University Law Center

On June 19, 1992, we and seven other members of the Georgetown University Law Center community landed in Tallinn, the capital of Estonia, to help the Estonian government draft laws to support a market economy. Our group consisted of six students, two professors, and an alumnus. The country to which we had come had declared its independence from the Soviet Union less than one year before. After fifty years of imposed communism, the Estonian leaders wanted to understand and adopt the basic foundations for a Western legal system that would support democratic and market institutions

Uszkodzenie nadnerczy w następstwie tępych urazów: wskaźnik ciężkości doznanych obrażeń

Introduction: Adrenal gland injuries (AGI) are seen increasingly frequently owing to advances in modern imaging techniques. This study describes a series of patients with blunt AGI, with the emphasis on AGI as a marker of injury severity, CT-radiographic classification of AGI and associated injury patterns. Material and methods: A retrospective review of blunt trauma patients with AGI was performed. Variables examined included demographics, mechanism of injury, length of hospital and ICU stay, clinical status on admission, AGI characteristics, associated injuries, complications, procedures, mortality and discharge disposition. Results: There were 29 AGI patients with a mean injury severity score of 25. The most common injury mechanisms were motor-vehicular collisions (15/29) and falls (5/29). Right-sided AGI (16/29) outnumbered left-sided (12/29) injuries. The most common CT-radiographic types of AGI were adrenal gland contusions and lacerations with limited "blush". While patterns of injuries differed between right and left-sided AGI, the mean number of injuries did not. The most common associated injuries included extremity (21/29), rib (20/29) and spinal fractures (18/29). Common procedures included orthopaedic fixation (10/29), vena cava filter (8/29) and tracheostomy (5/29). A median of two complications per patient was reported, including adrenal insufficiency in two patients. Mortality was 17%. The median hospital and ICU length of stay were 15 and 12 days, respectively. Conclusions: Adrenal gland injury is associated with significant morbidity and mortality. With modern imaging modalities capable of reliably detecting adrenal injury, the presence of AGI should be considered a marker of overall injury severity. The authors provide a CT-radiographic classification of adrenal injuries.Wstęp: W związku z postępem w zakresie nowoczesnych metod obrazowania coraz częściej stwierdza się uszkodzenia nadnerczy (AGI, adrenal gland injuries). W tym badaniu opisano grupę chorych, którzy doznali uszkodzenia nadnerczy w wyniku tępego urazu. Zwrócono szczególną uwagę na AGI jako wskaźnik ciężkości odniesionych obrażeń, klasyfikację AGI na podstawie tomografii komputerowej i charakter współistniejących obrażeń. Materiał i metody: Przeprowadzono retrospektywną analizę danych pacjentów, którzy doznali AGI w wyniku tępego urazu. W badaniu uwzględniono dane demograficzne, mechanizm powstania urazu, czas hospitalizacji oraz pobytu na oddziale intensywnej opieki medycznej, stan kliniczny w chwili przyjęcia do szpitala, cechy AGI, doznane obrażenia, powikłania, zastosowane procedury medyczne, odsetek zgonów i dalsze postępowanie. Wyniki: Do badania włączono 29 osób z AGI, u których średnia ocena ciężkości obrażeń wynosiła 25. Najczęstszymi przyczynami urazu były wypadki motocyklowe (15/29) i upadki (5/29). Liczba prawostronnych AGI (16/29) była wyższa niż liczba uszkodzeń lewostronnych (12/29). Najczęściej stwierdzanym rodzajem uszkodzeń AGI w badaniu tomograficznym było stłuczenie i rozdarcie narządu z niewielkim krwawieniem. Chociaż charakter uszkodzeń różnił się w zależności od prawo- lub lewostronnej lokalizacji AGI, średnia liczba uszkodzeń była taka sama. Najczęstszymi współwystępującymi obrażeniami były złamania kończyn (21/29), żeber (20/29) i kręgów (18/29). Do najczęściej wykonywanych procedur należały: unieruchomienie ortopedyczne (10/29), wszczepienie filtra do żyły głównej (8/29) i tracheostomia (5/29). Mediana liczby powikłań u poszczególnych chorych wynosiła 2 (włączając niewydolność nadnerczy u 2 osób). Odsetek zgonów wynosił 17%. Mediana okresu hospitalizacji i pobytu na oddziale intensywnej opieki medycznej wynosiła odpowiednio 15 i 12 dni. Wnioski: Uszkodzenie nadnerczy wiąże się ze znaczną chorobowością i śmiertelnością. Dostępne obecnie nowoczesne metody obrazowania umożliwiają wykrycie uszkodzeń nadnerczy. Należałoby rozważyć przyjęcie obecności AGI jako markera ciężkości doznanych obrażeń. Autorzy przedstawili klasyfikację uszkodzeń nadnerczy na podstawie badań tomograficznych

WHO consultation on group B Streptococcus vaccine development: Report from a meeting held on 27-28 April 2016.

Globally, group B Streptococcus (GBS) remains a leading cause of sepsis and meningitis in infants in the first 90days of life. Intrapartum antibiotic prophylaxis (IAP) for women at increased risk of transmitting GBS to their newborns has been effective in reducing part, but not all, of the GBS disease burden in many high income countries (HICs). In low- and middle-income countries (LMICs), IAP use is low. Immunization of pregnant women with a GBS vaccine represents an alternative strategy to protecting newborns and young infants, through transplacental antibody transfer and potentially by reducing new vaginal colonization. This vaccination strategy was first suggested in the 1970s and several potential GBS vaccines have completed phase I/II clinical trials. During the 2015 WHO Product Development for Vaccines Advisory Committee meeting, GBS was identified as a high priority for the development of a vaccine for maternal immunization because of the major public health burden posed by GBS in LMICs, and the high technical feasibility for successful development. Following this meeting, the first WHO technical consultation on GBS vaccines was held on the 27th and 28th of April 2016, to consider development pathways for such vaccines, focused on their potential role in reducing newborn and young infant deaths and possibly stillbirths in LMICs. Discussion topics included: (1) pathophysiology of disease; (2) current gaps in the knowledge of global disease burden and serotype distribution; (3) vaccine candidates under development; (4) design considerations for phase III trials; and (5) pathways to licensure, policy recommendations and use. Efforts to address gaps identified in each of these areas are needed to establish the public health need for, the development and deployment of, efficacious GBS vaccines. In particular, more work is required to understand the global disease burden of GBS-associated stillbirths, and to develop quality-assured standardized antibody assays to identify correlates of protection

Symptoms and quality of life in late stage Parkinson syndromes: a longitudinal community study of predictive factors

BACKGROUND Palliative care is increasingly offered earlier in the cancer trajectory but rarely in Idiopathic Parkinson's Disease(IPD), Progressive Supranuclear Palsy(PSP) or Multiple System Atrophy(MSA). There is little longitudinal data of people with late stage disease to understand levels of need. We aimed to determine how symptoms and quality of life of these patients change over time; and what demographic and clinical factors predicted changes. METHODS We recruited 82 patients into a longitudinal study, consenting patients with a diagnosis of IPD, MSA or PSP, stages 3-5 Hoehn and Yahr(H&Y). At baseline and then on up to 3 occasions over one year, we collected self-reported demographic, clinical, symptom, palliative and quality of life data, using Parkinson's specific and generic validated scales, including the Palliative care Outcome Scale (POS). We tested for predictors using multivariable analysis, adjusting for confounders. FINDINGS Over two thirds of patients had severe disability, over one third being wheelchair-bound/bedridden. Symptoms were highly prevalent in all conditions - mean (SD) of 10.6(4.0) symptoms. More than 50% of the MSA and PSP patients died over the year. Over the year, half of the patients showed either an upward (worsening, 24/60) or fluctuant (8/60) trajectory for POS and symptoms. The strongest predictors of higher levels of symptoms at the end of follow-up were initial scores on POS (AOR 1.30; 95%CI:1.05-1.60) and being male (AOR 5.18; 95% CI 1.17 to 22.92), both were more predictive than initial H&Y scores. INTERPRETATION The findings point to profound and complex mix of non-motor and motor symptoms in patients with late stage IPD, MSA and PSP. Symptoms are not resolved and half of the patients deteriorate. Palliative problems are predictive of future symptoms, suggesting that an early palliative assessment might help screen for those in need of earlier intervention

Root response to temperature extremes: association mapping of temperate maize (Zea mays L)

Little is known about the genetic control of the root architecture of maize (Zea mays L) and its response to temperature extremes. An association mapping panel, including 32 flint and 42 dent inbred lines, was characterized for root traits. The growth of axile and lateral roots was assessed non-destructively in growth pouches at 16°C (chilling), 28°C (control) and 36°C (heat). Association mapping was done using the PKOpt mixed-model associationmapping approach. Heat slowed down the development of seedling roots to a lesser extent than chilling, but differences between the heterotic groups were observed mainly at optimal temperature. Of 1,415 AFLP markers, 70 showed significant marker-trait associations and 90 showed significant marker-trait associations with temperature interaction effects. Compared to the flint lines, the dents showed stronger growth of axile roots, especially under optimal conditions, and carried more of the trait-increasing alleles for the length of axile roots. In contrast, Benjamin the flints accumulated more root dry weight at low temperature and exclusively carried the alleles favoring tolerance to chilling. A combination of inbreds carrying alleles positive for performance under contrasting temperature conditions should lead to a complementary effect in the hybrid and would increase adaptation to a wider range of temperature

Predictors of survival in progressive supranuclear palsy and multiple system atrophy: a systematic review and meta-analysis

Objective To undertake a systematic review and meta-analysis of studies that investigated prognostic factors and survival in patients with progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). Methods Publications of at least 10 patients with a likely or confirmed diagnosis of PSP or MSA were eligible for inclusion. Methodological quality was rated using a modified version of the Quality in Prognostic Studies tool. For frequently examined prognostic factors, HRs derived by univariate and multivariate analysis were pooled in separate subgroups; other results were synthesised narratively and HRs could not be reported here. Results Thirty-seven studies presenting findings on 6193 patients (1911 PSP, 4282 MSA) fulfilled the inclusion criteria. We identified the following variables as unfavourable predictors of survival. In PSP, PSP-Richardson’s phenotype (univariate HR 2.53; 95% CI 1.69 to 3.78), early dysphagia and early cognitive symptoms. In MSA, severe dysautonomia and early development of combined autonomic and motor features but not MSA phenotype (multivariate HR 1.22; 95% CI 0.83 to 1.80). In PSP and MSA, survival was predicted by early falls (multivariate HR 2.32; 95% CI 1.94 to 2.77), the Neuroprotection and Natural History in Parkinson Plus Syndromes Parkinson Plus Score and the Clinical Global Impression Disease Severity Score but not sex (multivariate HR 0.93; 95% CI 0.67 to 1.28). There was conflicting evidence regarding the prognostic effect of age at onset and stridor. Conclusion Several clinical variables were strongly associated with shorter survival in PSP and MSA. Results on most prognostic factors were consistent across methodologically diverse studies; however, the lack of commonality of prognostic factors investigated is a significant limitation

Phase I Study of Cetuximab, Irinotecan, and Vandetanib (ZD6474) as Therapy for Patients with Previously Treated Metastastic Colorectal Cancer

BACKGROUND: To determine the maximum tolerated dose (MTD) and safety, and explore efficacy and biomarkers of vandetanib with cetuximab and irinotecan in second-line metastatic colorectal cancer. METHODS: Vandetanib (an orally bioavailable VEGFR-2 and EGFR tyrosine kinases inhibitor) was combined at 100 mg, 200 mg, or 300 mg daily with standard dosed cetuximab and irinotecan (3+3 dose-escalation design). Ten patients were treated at the MTD and plasma angiogenesis biomarkers (VEGF, PlGF, bFGF, sVEGFR1, sVEGFR2, IL-1β, IL-6, IL-8, TNF-α, SDF1α) were measured before and after treatment. RESULTS: Twenty-seven patients were enrolled at 4 dose levels and the MTD. Two dose-limiting toxicities (grade 3 QTc prolongation and diarrhea) were detected at 300 mg of vandetanib with cetuximab and irinotecan resulting in 200 mg being the MTD. Seven percent of patients had a partial response, 59% stable disease and 34% progressed. Median progression-free survival was 3.6 months (95% CI, 3.2-5.6) and median overall survival was 10.5 months (95% CI, 5.1-20.7). Toxicities were fairly manageable with grade 3 or 4 diarrhea being most prominent (30%). Vandetanib and cetuximab treatment induced a sustained increase in plasma PlGF and a transient decrease in plasma sVEGFR1, but no changes in plasma VEGF and sVEGFR2. CONCLUSIONS: Vandetanib can be safely combined with cetuximab and irinotecan for metastatic colorectal cancer. Exploratory biomarker analyses suggest differential effects on certain plasma biomarkers for VEGFR inhibition when combined with EGFR blockade and a potential correlation between baseline sVEGFR1 and response. However, while the primary endpoint was safety, the observed efficacy raises concern for moving forward with this combination. TRIAL REGISTRATION: Clinicaltrials.gov NCT00436072

Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial

Combining biologic monoclonal antibodies with chemotherapeutic cytotoxic drugs provides clinical benefit to patients with advanced or metastatic colorectal cancer, but the optimal choice of the initial biologic therapy in previously untreated patients is unknown